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a LANGE medical book
Harper’s
Illustrated
Biochemistry THIRTY-FIRST EDITION
Victor W. Rodwell, PhD Peter J. Kennelly, PhD

Professor (Emeritus) of Biochemistry Professor
Purdue University Department of Biochemistry
West Lafayette, Indiana Virginia Tech
Blacksburg, Virginia
David A. Bender, PhD

P. Anthony Weil, PhD
Professor (Emeritus) of Nutritional Biochemistry
University College London Professor
London, United Kingdom Department of Molecular Physiology & Biophysics
Vanderbilt University
Nashville, Tennessee
Kathleen M. Botham, PhD, DSc
Professor (Emeritus) of Biochemistry
Department of Comparative Biomedical Sciences
Royal Veterinary College
University of London
London, United Kingdom
New York Chicago San Francisco Athens London Madrid Mexico City
Milan New Delhi Singapore Sydney Toronto
Rodwell_FM_pi-x.indd 1 10/04/18 4:36 pm

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Coauthors
Peter L. Gross, MD, MSc, FRCP(C) Robert K. Murray, MD, PhD
Associate Professor Professor (Emeritus) of Biochemistry
Department of Medicine University of Toronto
McMaster University Toronto, Ontario, Canada
Hamilton, Ontario, Canada
Margaret L. Rand, PhD
Molly Jacob MD, PhD Senior Associate Scientist
Professor and Head Division of Haematology/Oncology
Department of Biochemistry Hospital for Sick Children, Toronto, and Professor
Christian Medical College Department of Biochemistry
Bagayam, Vellore, Tamil Nadu, India University of Toronto, Toronto, Canada
Peter A. Mayes, PhD, DSc Joe Varghese, MBBS, MD

Professor (Emeritus) of Veterinary Biochemistry Professor
Royal Veterinary College Department of Biochemistry
University of London Christian Medical College
London, United Kingdom Bagayam, Vellore, Tamil Nadu, India
iii
Rodwell_FM_pi-x.indd 3 13/06/18 11:21 am

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Contents
Preface ix
S E C T I O N
10 The Biochemical Roles of Transition
Structures & Functions of Metals 92
I Proteins & Enzymes 1 Peter J. Kennelly, PhD
1 Biochemistry & Medicine 1 S E C T I O N

Victor W. Rodwell, PhD, & Robert K. Murray, MD, PhD
2 Water & pH 6
Peter J. Kennelly, PhD & Victor W. Rodwell, PhD
III Bioenergetics 105
11 Bioenergetics: The Role of ATP 105

3 Amino Acids & Peptides 14 Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc
12 Biologic Oxidation 111
4 Proteins: Determination of Primary Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc
Structure 23
Peter J. Kennelly, PhD & Victor W. Rodwell, PhD 13 The Respiratory Chain & Oxidative
Phosphorylation 117
5 Proteins: Higher Orders of Structure 33 Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc
S E C T I O N
Metabolism of
IV
S E C T I O N
Enzymes: Kinetics,
Carbohydrates 129
II Mechanism, Regulation, &
Role of Transition Metals 47
14 Overview of Metabolism & the Provision of
6 Proteins: Myoglobin & Hemoglobin 47 Metabolic Fuels 129
Peter J. Kennelly, PhD & Victor W. Rodwell, PhD David A. Bender, PhD & Peter A. Mayes, PhD, DSc
7 Enzymes: Mechanism of Action 56 15 Carbohydrates of Physiological

Peter J. Kennelly, PhD & Victor W. Rodwell, PhD Significance 141
David A. Bender, PhD & Peter A. Mayes, PhD, DSc
8 Enzymes: Kinetics 68
Victor W. Rodwell, PhD 16 The Citric Acid Cycle: The Central Pathway
of Carbohydrate, Lipid, & Amino Acid
9 Enzymes: Regulation of Activities 82 Metabolism 150
Peter J. Kennelly, PhD & Victor W. Rodwell, PhD David A. Bender, PhD & Peter A. Mayes, PhD, DSc

vi CONTENTS
17 Glycolysis & the Oxidation of Pyruvate 157 28 Catabolism of Proteins & of Amino Acid
David A. Bender, PhD & Peter A. Mayes, PhD, DSc Nitrogen 269
Victor W. Rodwell, PhD
18 Metabolism of Glycogen 164
David A. Bender, PhD & Peter A. Mayes, PhD, DSc 29 Catabolism of the Carbon Skeletons of
Amino Acids 280
19 Gluconeogenesis & the Control of Victor W. Rodwell, PhD
Blood Glucose 172
David A. Bender, PhD & Peter A. Mayes, PhD, DSc 30 Conversion of Amino Acids to Specialized
Products 296
20 The Pentose Phosphate Pathway & Other Victor W. Rodwell, PhD
Pathways of Hexose Metabolism 182
David A. Bender, PhD & Peter A. Mayes, PhD, DSc 31 Porphyrins & Bile Pigments 305
Victor W. Rodwell, PhD & Robert K. Murray, MD, PhD
S E C T I O N
V Metabolism of Lipids 195

S E C T I O N
Structure, Function, &
21 Lipids of Physiologic Significance 195

Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc
VII Replication of Informational
Macromolecules 319
32 Nucleotides 319
22 Oxidation of Fatty Acids: Ketogenesis 207 Victor W. Rodwell, PhD
33 Metabolism of Purine & Pyrimidine
23 Biosynthesis of Fatty Acids & Nucleotides 327
Eicosanoids 216 Victor W. Rodwell, PhD
34 Nucleic Acid Structure & Function 338
24 Metabolism of Acylglycerols & P. Anthony Weil, PhD
Sphingolipids 229
Kathleen M. Botham, PhD, DSc & Peter A. Mayes, PhD, DSc 35 DNA Organization, Replication, &
Repair 350
25 Lipid Transport & Storage 236 P. Anthony Weil, PhD
36 RNA Synthesis, Processing, &
26 Cholesterol Synthesis, Transport, & Modification 374
Excretion 249 P. Anthony Weil, PhD
37 Protein Synthesis & the Genetic Code 393
S E C T I O N
Metabolism of Proteins &
VI Amino Acids 263 38 Regulation of Gene Expression 409
27 Biosynthesis of the Nutritionally Nonessential 39 Molecular Genetics, Recombinant DNA, &

Amino Acids 263 Genomic Technology 432
Victor W. Rodwell, PhD P. Anthony Weil, PhD

CONTENTS vii
S E C T I O N S E C T I O N
Biochemistry of
VIII Extracellular & Intracellular

Communication 459 X Special Topics (B) 573
49 Intracellular Traffic & Sorting of Proteins 573

40 Membranes: Structure &
Kathleen M. Botham, PhD, DSc & Robert K. Murray, MD, PhD
Function 459
50 The Extracellular Matrix 592
Kathleen M. Botham, PhD, DSc & Robert K. Murray, MD, PhD
41 The Diversity of the Endocrine
System 480
51 Muscle & the Cytoskeleton 611
Peter J. Kennelly, PhD and Robert K. Murray, MD, PhD
42 Hormone Action & Signal

52 Plasma Proteins & Immunoglobulins 627
Transduction 500
Peter J. Kennelly, PhD, Robert K. Murray, MD, PhD,
P. Anthony Weil, PhD Molly Jacob, MBBS, MD, PhD & Joe Varghese, MBBS, MD
53 Red Blood Cells 646

Peter J. Kennelly, PhD & Robert K. Murray, MD, PhD
S E C T I O N
IX Special Topics (A) 519 54 White Blood Cells 656

Peter J. Kennelly, PhD & Robert K. Murray, MD, PhD
43 Nutrition, Digestion, &

S E C T I O N
Absorption 519
David A. Bender, PhD & Peter A. Mayes, PhD, DSc
44 Micronutrients: Vitamins &

XI Special Topics (C) 669
Minerals 527 55 Hemostasis & Thrombosis 669

Peter L. Gross, MD, MSc, FRCP(C),
P. Anthony Weil, PhD & Margaret L. Rand, PhD
45 Free Radicals & Antioxidant
Nutrients 541 56 Cancer: An Overview 681
David A. Bender, PhD Molly Jacob, MD, PhD, Joe Varghese, MBBS, MD &
46 Glycoproteins 546
David A. Bender, PhD & Robert K. Murray, MD, PhD 57 The Biochemistry of Aging 707
Peter J. Kennelly, PhD
47 Metabolism of Xenobiotics 556
David A. Bender, PhD & Robert K. Murray, MD, PhD 58 Biochemical Case Histories 719
48 Clinical Biochemistry 560
David A. Bender, PhD & Robert K. Murray, MD, PhD The Answer Bank 731
Index 735
Rodwell_FM_pi-x.indd 7 13/06/18 11:24 am

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Preface
The authors and publishers are pleased to present the those of blood cells and plasma, which contained extensive
thirty-first edition of Harper’s Illustrated Biochemistry. The content on metal ion adsorption and trafficking, especially of
first edition, entitled Harper’s Biochemistry, was published in iron and copper. Since approximately a third of all proteins
1939 under the sole authorship of Dr Harold Harper at the are metalloproteins, new Chapter 10 explicitly addresses the
University of California School of Medicine, San Francisco, importance and overall pervasiveness of transition metals.
California. Presently entitled Harper’s Illustrated Biochemistry, Given the overlap with the topics of protein structure and
the book continues, as originally intended, to provide a concise of enzyme reaction mechanisms, new Chapter 10 now fol-
survey of aspects of biochemistry most relevant to the study lows the three chapters on enzymes as the final chapter in
of medicine. Various authors have contributed to subsequent Section II, now renamed Enzymes: Kinetics, Mechanism,
editions of this medically oriented biochemistry text, which is Regulation, & Role of Transition Metals.
now observing its 79th year.
Organization of the Book
Cover Illustration for All 58 chapters of the thirty-first edition place major empha-
the Thirty-first Edition sis on the medical relevance of biochemistry. Topics are orga-
The illustration on the cover of the thirty-first edition, the struc- nized under eleven major headings. Both to assist study and
ture of Zika virus protein determined at 3.8 Å resolution, was to facilitate retention of the contained information, Questions
generously prepared and provided by Lei Sun. The supporting follow each Section. An Answer Bankk follows the Appendix.
data appeared in: Sirohi D, Chen Z, Sun L, Klose T, Pierson Section I includes a brief history of biochemistry, and
TC, Rossmann MG, Kuhn RJ: “The 3.8 Å resolution cryo-EM emphasizes the interrelationships between biochemistry
structure of Zika virus protein”, Science 2016;352:497-470. and medicine. Water, the importance of homeostasis of
Together with the Zika virus, first recovered in the Zika valley intracellular pH are reviewed, and the various orders of
of Uganda, the viruses responsible for yellow fever, West Nile protein structure are addressed.
fever, and dengue fever are members of the Flavivridae family Section II begins with a chapter on hemoglobin. Four
of positive-strand DNA viruses. The cover illustration indicates chapters next address the kinetics, mechanism of action,
the resolving power of cryo-electron microscopy (cryo-EM). and metabolic regulation of enzymes, and the role of metal
More importantly, it recognizes the medical significance of ions in multiple aspects of intermediary metabolism.
infection by the Zika virus, which in pregnant women can result
Section III addresses bioenergetics and the role of high
in a significant risk of congenital microcephaly and associated
energy phosphates in energy capture and transfer, the
severe mental impairment. While Zika virus typically is trans-
oxidation–reduction reactions involved in biologic
mitted by the bite of an infected mosquito, emerging evidence
oxidation, and metabolic details of energy capture via the
suggests that under certain conditions the Zika virus may also
respiratory chain and oxidative phosphorylation.
be transmitted between human subjects.
Section IV considers the metabolism of carbohydrates
via glycolysis, the citric acid cycle, the pentose phosphate
Changes in the Thirty-first Edition pathway, glycogen metabolism, gluconeogenesis, and the
As always, Harper’s Illustrated Biochemistry continues to control of blood glucose.
emphasize the close relationship of biochemistry to the Section V outlines the nature of simple and complex
understanding of diseases, their pathology and the practice of lipids, lipid transport and storage, the biosynthesis and
medicine. The contents of most chapters have been updated degradation of fatty acids and more complex lipids, and
and provide to the reader the most current and pertinent the reactions and metabolic regulation of cholesterol
information. Toward that end, we have replaced Chapter 10 biosynthesis and transport in human subjects.
“Bioinformatics and Computational Biology,” most of whose Section VI discusses protein catabolism, urea
programs and topics (for example protein and nucleotide biosynthesis, and the catabolism of amino acids and
sequence comparisons and in silico approaches in drug stresses the medically significant metabolic disorders
design) are available on line or are now common knowledge. associated with their incomplete catabolism. The final
Its replacement, new Chapter 10 “Biochemistry of Transition chapter considers the biochemistry of the porphyrins
Metals,” incorporates material from several chapters, notably and bile pigments.
ix

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x PREFACE
Section VII first outlines the structure and function Section XI includes hemostasis and thrombosis, an
of nucleotides and nucleic acids, then details overview of cancer, the biochemistry of aging, and a
DNA replication and repair, RNA synthesis and selection of case histories.
modification, protein synthesis, the principles of
recombinant DNA technology, and the regulation of
gene expression.
Acknowledgments
Section VIII considers aspects of extracellular and The authors thank Michael Weitz for his role in the planning
intracellular communication. Specific topics include of this edition and Peter Boyle for overseeing its preparation
membrane structure and function, the molecular bases for publication. We also thank Surbhi Mittal and Jyoti Shaw
of the actions of hormones, and signal transduction. at Cenveo Publisher Services for their efforts in managing
editing, typesetting, and artwork. We gratefully acknowl-
Sections IX, X, & XI address fourteen topics of
edge numerous suggestions and corrections received from
significant medical importance.
students and colleagues from around the world, especially
Section IX discusses nutrition, digestion, and those of Dr. Karthikeyan Pethusamy of the All India Institute
absorption, micronutrients including vitamins free of Medical Sciences, New Delhi, India.
radicals and antioxidants, glycoproteins, the metabolism
of xenobiotics, and clinical biochemistry. Victor W. Rodwell
Section X addresses intracellular traffic and the sorting David A. Bender
of proteins, the extracellular matrix, muscle and the Kathleen M. Botham
cytoskeleton, plasma proteins and immunoglobulins, Peter J. Kennelly
and the biochemistry of red cells and of white cells. P. Anthony Weil

S E C T I O N
Structures & Functions
I of Proteins & Enzymes
1
C H A P T E R
Biochemistry & Medicine

Victor W. Rodwell, PhD, & Robert K. Murray, MD, PhD
O B J EC T IVES ■■ Understand the importance of the ability of cell-free extracts of yeast to

ferment sugars, an observation that enabled discovery of the intermediates of
After studying this chapter, fermentation, glycolysis, and other metabolic pathways.
you should be able to: ■■ Appreciate the scope of biochemistry and its central role in the life sciences,
and that biochemistry and medicine are intimately related disciplines.
■■ Appreciate that biochemistry integrates knowledge of the chemical processes
in living cells with strategies to maintain health, understand disease, identify
potential therapies, and enhance our understanding of the origins of life on
earth.
■■ Describe how genetic approaches have been critical for elucidating many areas
of biochemistry, and how the Human Genome Project has furthered advances
in numerous aspects of biology and medicine.
BIOMEDICAL IMPORTANCE DISCOVERY THAT A CELL-FREE

Biochemistry and medicine enjoy a mutually cooperative EXTRACT OF YEAST CAN
relationship. Biochemical studies have illuminated many FERMENT SUGAR
aspects of health and disease, and the study of various aspects
of health and disease has opened up new areas of biochem- Although the ability of yeast to “ferment” various sugars
istry. The medical relevance of biochemistry both in normal to ethyl alcohol has been known for millennia, only com-
and abnormal situations is emphasized throughout this book. paratively recently did this process initiate the science of
Biochemistry makes significant contributions to the fields of biochemistry. The great French microbiologist Louis Pasteur
cell biology, physiology, immunology, microbiology, pharma- maintained that fermentation could only occur in intact cells.
cology, toxicology, and epidemiology, as well as the fields of However, in 1899, the brothers Büchner discovered that fer-
inflammation, cell injury, and cancer. These close relationships mentation could occur in the absence of intact cells when they
emphasize that life, as we know it, depends on biochemical stored a yeast extract in a crock of concentrated sugar solu-
reactions and processes. tion, added as a preservative. Overnight, the contents of the
crock fermented, spilled over the laboratory bench and floor,
Rodwell_CH01_p001-005.indd 1 30/03/18 8:57 am

2 SECTION I Structures & Functions of Proteins & Enzymes
and dramatically demonstrated that fermentation can proceed the interrelationship of biochemistry and medicine is a wide,
in the absence of an intact cell. This discovery unleashed an two-way street. Biochemical studies have illuminated many
avalanche of research that initiated the science of biochemis- aspects of health and disease, and conversely, the study of vari-
try. Investigations revealed the vital roles of inorganic phos- ous aspects of health and disease has opened up new areas of
phate, ADP, ATP, and NAD(H), and ultimately identified biochemistry (Figure 1–1). An early example of how investiga-
the phosphorylated sugars and the chemical reactions and tion of protein structure and function revealed the single dif-
enzymes that convert glucose to pyruvate (glycolysis) or to ference in amino acid sequence between normal hemoglobin
ethanol and CO2 (fermentation). Research beginning in the and sickle cell hemoglobin. Subsequent analysis of numerous
1930s identified the intermediates of the citric acid cycle and variant sickle cell and other hemoglobins has contributed sig-
of urea biosynthesis, and revealed the essential roles of certain nificantly to our understanding of the structure and function
vitamin-derived cofactors or “coenzymes” such as thiamin both of hemoglobin and of other proteins. During the early
pyrophosphate, riboflavin, and ultimately coenzyme A, coen- 1900s the English physician Archibald Garrod studied patients
zyme Q, and cobamide coenzyme. The 1950s revealed how with the relatively rare disorders of alkaptonuria, albinism, cys-
complex carbohydrates are synthesized from, and broken tinuria, and pentosuria, and established that these conditions
down into simple sugars, and the pathways for biosynthesis were genetically determined. Garrod designated these condi-
of pentoses, and the catabolism of amino acids and fatty acids. tions as inborn errors of metabolism. His insights provided
Investigators employed animal models, perfused intact a foundation for the development of the field of human bio-
organs, tissue slices, cell homogenates and their subfractions, chemical genetics. A more recent example was investigation
and subsequently purified enzymes. Advances were enhanced of the genetic and molecular basis of familial hypercholester-
by the development of analytical ultracentrifugation, paper olemia, a disease that results in early-onset atherosclerosis. In
and other forms of chromatography, and the post-World addition to clarifying different genetic mutations responsible
War II availability of radioisotopes, principally 14C, 3H, and 32P, for this disease, this provided a deeper understanding of cell
as “tracers” to identify the intermediates in complex pathways receptors and mechanisms of uptake, not only of cholesterol
such as that of cholesterol biosynthesis. X-ray crystallogra- but also of how other molecules cross cell membranes. Stud-
phy was then used to solve the three-dimensional structures ies of oncogenes and tumor suppressor genes in cancer cells
of numerous proteins, polynucleotides, enzymes, and viruses. have directed attention to the molecular mechanisms involved
Genetic advances that followed the realization that DNA was a in the control of normal cell growth. These examples illustrate
double helix include the polymerase chain reaction, and trans- how the study of disease can open up areas of basic biochemi-
genic animals or those with gene knockouts. The methods used cal research. Science provides physicians and other workers
to prepare, analyze, purify, and identify metabolites and the in health care and biology with a foundation that impacts
activities of natural and recombinant enzymes and their three- practice, stimulates curiosity, and promotes the adoption of
dimensional structures are discussed in the following chapters. scientific approaches for continued learning.
BIOCHEMICAL PROCESSES
BIOCHEMISTRY & MEDICINE UNDERLIE HUMAN HEALTH
HAVE PROVIDED MUTUAL
ADVANCES Biochemical Research Impacts
The two major concerns for workers in the health sciences— Nutrition & Preventive Medicine
and particularly physicians—are the understanding and The World Health Organization (WHO) defines health as a state
maintenance of health and effective treatment of disease. Bio- of “complete physical, mental, and social well-being and not
chemistry impacts both of these fundamental concerns, and merely the absence of disease and infirmity.” From a biochemical
Biochemistry
Nucleic
acids Proteins Lipids Carbohydrates
Genetic Sickle cell Athero- Diabetes

diseases anemia sclerosis mellitus
Medicine
FIGURE 1–1 A two-way street connects biochemistry and medicine. Knowledge of the biochemical topics listed above the green
line of the diagram has clarified our understanding of the diseases shown below the green line. Conversely, analyses of the diseases have cast
light on many areas of biochemistry. Note that sickle cell anemia is a genetic disease, and that both atherosclerosis and diabetes mellitus have
genetic components.

CHAPTER 1 Biochemistry & Medicine 3
viewpoint, health may be considered that situation in which all announcement that over 90% of the genome had been sequenced.
of the many thousands of intra- and extracellular reactions that This effort was headed by the International Human Genome
occur in the body are proceeding at rates commensurate with Sequencing Consortium and by Celera Genomics. Except for
the organism’s survival under pressure from both internal and a few gaps, the sequence of the entire human genome was
external challenges. The maintenance of health requires optimal completed in 2003, just 50 years after the description of the
dietary intake of vitamins, certain amino acids and fatty acids, double-helical nature of DNA by Watson and Crick. The
various minerals, and water. Understanding nutrition depends implications for biochemistry, medicine, and indeed for all
to a great extent on knowledge of biochemistry, and the sciences of biology, are virtually unlimited. For example, the ability
of biochemistry and nutrition share a focus on these chemicals. to isolate and sequence a gene and to investigate its structure
Recent increasing emphasis on systematic attempts to maintain and function by sequencing and “gene knockout” experi-
health and forestall disease, or preventive medicine, includes ments have revealed previously unknown genes and their
nutritional approaches to the prevention of diseases such as products, and new insights have been gained concerning
atherosclerosis and cancer. human evolution and procedures for identifying disease-
related genes.
Most Diseases Have a Biochemical Basis Major advances in biochemistry and understanding
Apart from infectious organisms and environmental pollut- human health and disease continue to be made by mutation
ants, many diseases are manifestations of abnormalities in genes, of the genomes of model organisms such as yeast, the fruit
proteins, chemical reactions, or biochemical processes, each fly Drosophila melanogaster, the roundworm Caenorhabditis
of which can adversely affect one or more critical biochemical elegans, and the zebra fish, all organisms that can be geneti-
functions. Examples of disturbances in human biochemistry cally manipulated to provide insight into the functions of
responsible for diseases or other debilitating conditions include individual genes. These advances can potentially provide
electrolyte imbalance, defective nutrient ingestion or absorp- clues to curing human diseases such as cancer and Alzheimer
tion, hormonal imbalances, toxic chemicals or biologic agents, disease. Figure 1–2 highlights areas that have developed or
and DNA-based genetic disorders. To address these challenges, accelerated as a direct result of progress made in the Human
biochemical research continues to be interwoven with studies in Genome Project (HGP). New “-omics” fields focus on com-
disciplines such as genetics, cell biology, immunology, nutrition, prehensive study of the structures and functions of the mol-
pathology, and pharmacology. In addition, many biochemists are ecules with which each is concerned. The products of genes
vitally interested in contributing to solutions to key issues such (RNA molecules and proteins) are being studied using the
as the ultimate survival of mankind, and educating the public to techniques of transcriptomics and proteomics. A spectacu-
support use of the scientific method in solving environmental lar example of the speed of progress in transcriptomics is the
and other major problems that confront our civilization. explosion of knowledge about small RNA molecules as regu-
lators of gene activity. Other -omics fields include glycomics,
lipidomics, metabolomics, nutrigenomics, and pharma-
Impact of the Human Genome Project cogenomics. To keep pace with the information generated,
on Biochemistry, Biology, & Medicine bioinformatics has received much attention. Other related
Initially unanticipated rapid progress in the late 1990s in fields to which the impetus from the HGP has carried over are
sequencing the human genome led in the mid-2000s to the biotechnology, bioengineering, biophysics, and bioethics.
Transcriptomics Proteomics Glycomics Lipidomics
Metabolomics Nutrigenomics
Pharmacogenomics Bioinformatics
HGP
(Genomics)
Bioengineering Biotechnology
Biophysics
Bioethics
Stem cell biology

Gene therapy
Nanotechnology
Molecular diagnostics Systems biology Synthetic biology
FIGURE 1–2 The Human Genome Project (HGP) has influenced many disciplines and areas of research. Biochemistry is not listed
since it predates commencement of the HGP, but disciplines such as bioinformatics, genomics, glycomics, lipidomics, metabolomics, molecular
diagnostics, proteomics, and transcriptomics are nevertheless active areas of biochemical research.

Definitions of these -omics fields and other terms appear in Bioinformatics: The discipline concerned with the collection,
the Glossary of this chapter. Nanotechnology is an active area, storage, and analysis of biologic data, for example, DNA, RNA,
which, for example, may provide novel methods of diagnosis and protein sequences.
and treatment for cancer and other disorders. Stem cell biol- Biophysics: The application of physics and its techniques to biology
and medicine.
ogy is at the center of much current research. Gene therapy
Biotechnology: The field in which biochemical, engineering, and
has yet to deliver the promise that it appears to offer, but it
other approaches are combined to develop biologic products of
seems probable that ultimately will occur. Many new molecu- use in medicine and industry.
lar diagnostic tests have developed in areas such as genetic, Gene Therapy: Applies to the use of genetically engineered genes to
microbiologic, and immunologic testing and diagnosis. treat various diseases.
Systems biology is also burgeoning. The outcomes of research Genomics: The genome is the complete set of genes of an organism,
in the various areas mentioned above will impact tremen- and genomics is the in-depth study of the structures and
dously the future of biology, medicine, and the health sciences. functions of genomes.
Synthetic biology offers the potential for creating living organ- Glycomics: The glycome is the total complement of simple and
isms, initially small bacteria, from genetic material in vitro complex carbohydrates in an organism. Glycomics is the
that might carry out specific tasks such as cleansing petroleum systematic study of the structures and functions of glycomes
such as the human glycome.
spills. All of the above make the 21st century an exhilarating
Lipidomics: The lipidome is the complete complement of lipids
time to be directly involved in biology and medicine.
found in an organism. Lipidomics is the in-depth study of the
structures and functions of all members of the lipidome and
SUMMARY their interactions, in both health and disease.
Metabolomics: The metabolome is the complete complement of
■■ Biochemistry is the science concerned with the molecules metabolites (small molecules involved in metabolism) present
present in living organisms, individual chemical reactions and in an organism. Metabolomics is the in-depth study of their
their enzyme catalysts, and the expression and regulation of structures, functions, and changes in various metabolic states.
each metabolic process. Biochemistry has become the basic Molecular Diagnostics: Refers to the use of molecular approaches such
language of all biologic sciences. as DNA probes to assist in the diagnosis of various biochemical,
■■ Despite the focus on human biochemistry in this text, genetic, immunologic, microbiologic, and other medical conditions.
biochemistry concerns the entire spectrum of life forms, from Nanotechnology: The development and application to medicine
viruses, bacteria, and plants to complex eukaryotes such as and to other areas of devices such as nanoshells, which are only a
human beings. few nanometers in size (10–9 m = 1 nm).
Nutrigenomics: The systematic study of the effects of nutrients on
■■ Biochemistry, medicine, and other health care disciplines
genetic expression and of the effects of genetic variations on the
are intimately related. Health in all species depends on a
metabolism of nutrients.
harmonious balance of the biochemical reactions occurring in
Pharmacogenomics: The use of genomic information and
the body, while disease reflects abnormalities in biomolecules,
technologies to optimize the discovery and development of new
biochemical reactions, or biochemical processes.
drugs and drug targets.
■■ Advances in biochemical knowledge have illuminated many Proteomics: The proteome is the complete complement of proteins
areas of medicine, and the study of diseases has often revealed of an organism. Proteomics is the systematic study of the
previously unsuspected aspects of biochemistry. structures and functions of proteomes and their variations in
■■ Biochemical approaches are often fundamental in illuminating health and disease.
the causes of diseases and in designing appropriate therapy. Stem Cell Biology: Stem cells are undifferentiated cells that have the
Biochemical laboratory tests also represent an integral potential to self-renew and to differentiate into any of the adult
component of diagnosis and monitoring of treatment. cells of an organism. Stem cell biology concerns the biology of
■■ A sound knowledge of biochemistry and of other related basic stem cells and their potential for treating various diseases.
disciplines is essential for the rational practice of medicine and Synthetic Biology: The field that combines biomolecular techniques
related health sciences. with engineering approaches to build new biologic functions and
systems.
■■ Results of the HGP and of research in related areas will have
Systems Biology: The field concerns complex biologic systems
a profound influence on the future of biology, medicine, and
studied as integrated entities.
other health sciences.
Transcriptomics: The comprehensive study of the transcriptome,
■■ Genomic research on model organisms such as yeast, the fruit the complete set of RNA transcripts produced by the genome
fly D. melanogaster, the roundworm C. elegans, and the zebra during a fixed period of time.
fish provides insight into understanding human diseases.
APPENDIX
GLOSSARY Shown are selected examples of databases that assemble, annotate,
Bioengineering: The application of engineering to biology and and analyze data of biomedical importance.
medicine. ENCODE: ENCyclopedia Of DNA Elements. A collaborative effort
Bioethics: The area of ethics that is concerned with the application that combines laboratory and computational approaches to
of moral and ethical principles to biology and medicine. identify every functional element in the human genome.

CHAPTER 1 Biochemistry & Medicine 5
GenBank: Protein sequence database of the National Institutes of ISDB: International Sequence DataBase that incorporates DNA
Health (NIH) stores all known biologic nucleotide sequences and databases of Japan and of the European Molecular Biology
their translations in a searchable form. Laboratory (EMBL).
HapMap: Haplotype Map, an international effort to identify single PDB: Protein DataBase. Three-dimensional structures of proteins,
nucleotide polymorphisms (SNPs) associated with common polynucleotides, and other macromolecules, including proteins
human diseases and differential responses to pharmaceuticals. bound to substrates, inhibitors, or other proteins.

2
C H A P T E R
Water & pH
O B J EC T IVES ■■ Describe the properties of water that account for its surface tension, viscosity,
liquid state at ambient temperature, and solvent power.
After studying this chapter, ■■ Use structural formulas to represent several organic compounds that can serve
you should be able to: as hydrogen bond donors or acceptors.
■■ Explain the role played by entropy in the orientation, in an aqueous
environment, of the polar and nonpolar regions of macromolecules.
■■ Indicate the quantitative contributions of salt bridges, hydrophobic
interactions, and van der Waals forces to the stability of macromolecules.
■■ Explain the relationship of pH to acidity, alkalinity, and the quantitative
determinants that characterize weak and strong acids.
■■ Calculate the shift in pH that accompanies the addition of a given quantity of
acid or base to the pH of a buffered solution.
■■ Describe what buffers do, how they do it, and the conditions under which a
buffer is most effective under physiologic or other conditions.
■■ Illustrate how the Henderson-Hasselbalch equation can be used to calculate
the net charge on a polyelectrolyte at a given pH.
BIOMEDICAL IMPORTANCE the pH of extracellular fluid between 7.35 and 7.45. Suspected
disturbances of acid-base balance are verified by measuring
Water is the predominant chemical component of living the pH of arterial blood and the CO2 content of venous blood.
organisms. Its unique physical properties, which include the Causes of acidosis (blood pH <7.35) include diabetic ketosis
ability to solvate a wide range of organic and inorganic mol- and lactic acidosis. Alkalosis (pH >7.45) may follow vomiting
ecules, derive from water’s dipolar structure and exceptional of acidic gastric contents.
capacity for forming hydrogen bonds. The manner in which
water interacts with a solvated biomolecule influences the
structure both of the biomolecule and of water itself. An excel- WATER IS AN IDEAL BIOLOGIC
lent nucleophile, water is a reactant or product in many met- SOLVENT
abolic reactions. Regulation of water balance depends upon
hypothalamic mechanisms that control thirst, on antidiuretic Water Molecules Form Dipoles
hormone (ADH), on retention or excretion of water by the A water molecule is an irregular, slightly skewed tetrahedron
kidneys, and on evaporative loss. Nephrogenic diabetes insipi- with oxygen at its center (Figure 2–1). The two hydrogens and
dus, which involves the inability to concentrate urine or adjust the unshared electrons of the remaining two sp3-hybridized
to subtle changes in extracellular fluid osmolarity, results from orbitals occupy the corners of the tetrahedron. The 105° angle
the unresponsiveness of renal tubular osmoreceptors to ADH. between the two hydrogen atoms differs slightly from the ideal
Water has a slight propensity to dissociate into hydroxide tetrahedral angle, 109.5°. Ammonia is also tetrahedral, with a
ions and protons. The concentration of protons, or acidity, of 107° angle between its three hydrogens. The strongly electro-
aqueous solutions is generally reported using the logarithmic negative oxygen atom in a water molecule attracts electrons
pH scale. Bicarbonate and other buffers normally maintain away from the hydrogen nuclei, leaving them with a partial

CHAPTER 2 Water & pH 7
H
CH3 CH2 O H O
2e H
2e
H
H
CH3 CH2 O H O
105°
CH2 CH3
H
FIGURE 2–1 The water molecule has tetrahedral geometry. R R II

C O H N
positive charge, while its two unshared electron pairs consti- RI R III
tute a region of local negative charge.
A molecule with electrical charge distributed asymmet- FIGURE 2–3 Additional polar groups participate in hydro-
gen bonding. Shown are hydrogen bonds formed between alcohol
rically about its structure is referred to as a dipole. Water’s and water, between two molecules of ethanol, and between the
strong dipole is responsible for its high dielectric constant. peptide carbonyl oxygen and the peptide nitrogen hydrogen of an
As described quantitatively by Coulomb’s law, the strength of adjacent amino acid.
interaction F between oppositely charged particles is inversely
proportionate to the dielectric constant ε of the surrounding can participate in hydrogen bonding. The oxygen atoms of
medium. The dielectric constant for a vacuum is essentially aldehydes, ketones, and amides, for example, provide lone
unity; for hexane it is 1.9; for ethanol, 24.3; and for water pairs of electrons that can serve as hydrogen acceptors. Alco-
at 25°C, 78.5. Water therefore greatly decreases the force of hols, carboxylic acids, and amines can serve both as hydrogen
attraction between charged and polar species relative to water- acceptors and as donors of unshielded hydrogen atoms for for-
free environments with lower dielectric constants. Its strong mation of hydrogen bonds (Figure 2–3).
dipole and high dielectric constant enable water to dissolve
large quantities of charged compounds such as salts.
INTERACTION WITH WATER
Water Molecules Form Hydrogen Bonds INFLUENCES THE STRUCTURE
A partially unshielded hydrogen nucleus covalently bound to
an electron-withdrawing oxygen or nitrogen atom can interact OF BIOMOLECULES
with an unshared electron pair on another oxygen or nitrogen
atom to form a hydrogen bond. Since water molecules con-
Covalent and Noncovalent Bonds
tain both of these features, hydrogen bonding favors the self- Stabilize Biologic Molecules
association of water molecules into ordered arrays (Figure 2–2). The covalent bond is the strongest force that holds molecules
Hydrogen bonding profoundly influences the physical proper- together (Table 2–1). Noncovalent forces, while of lesser mag-
ties of water and accounts for its relatively high viscosity, sur- nitude, make significant contributions to the structure, stabil-
face tension, and boiling point. On average, each molecule in ity, and functional competence of macromolecules in living
liquid water associates through hydrogen bonds with 3.5 oth- cells. These forces, which can be either attractive or repulsive,
ers. These bonds are both relatively weak and transient, with a involve interactions both within the biomolecule and between
half-life of a few picoseconds. Rupture of a hydrogen bond in it and the water that forms the principal component of the sur-
liquid water requires only about 4.5 kcal/mol, less than 5% of rounding environment.
the energy required to rupture a covalent O—H bond.
Hydrogen bonding enables water to dissolve many TABLE 2–1 Bond Energies for Atoms of Biologic
organic biomolecules that contain functional groups which Significance
Energy Energy
H H H H
Bond Type (kcal/mol) Bond Type (kcal/mol)
O O H
H H H O O—O 34 —O
O— 96
O H O S—S 51 C—H 99
H O H H
H O C—N 70 —S
C— 108
H
S—H 81 O—H 110
FIGURE 2–2 Water molecules self-associate via hydrogen C—C 82 —C
C— 147
bonds. Shown are the association of two water molecules (left) and
a hydrogen-bonded cluster of four water molecules (right). Notice C—O 84 —N
C— 147
that water can serve simultaneously both as a hydrogen donor and N—H 94 —O
C— 164
as a hydrogen acceptor.

Biomolecules Fold to Position Polar & .50
Interaction energy (kcaI mol–1)

Charged Groups on Their Surfaces .25
Most biomolecules are amphipathic; that is, they possess
regions rich in charged or polar functional groups as well as 0
regions with hydrophobic character. Proteins tend to fold with
A
the R-groups of amino acids with hydrophobic side chains in –0.25
the interior. Amino acids with charged or polar amino acid
side chains (eg, arginine, glutamate, serine, see Table 3–1) –0.50
generally are present on the surface in contact with water. A
similar pattern prevails in a phospholipid bilayer where the 3.0 4.0 5.0 6.0 7.0 8.0
R (Å)
charged “head groups” of phosphatidylserine or phosphatidyl-
ethanolamine contact water while their hydrophobic fatty acyl FIGURE 2–4 The strength of van der Waals interactions var-
side chains cluster together, excluding water (see Figure 40–5). ies with the distance, R, between interacting species. The force of
This pattern maximizes the opportunities for the formation interaction between interacting species increases with decreasing
of energetically favorable charge-dipole, dipole-dipole, and distance between them until they are separated by the van der Waals
hydrogen bonding interactions between polar groups on the contact distance (see arrow marked A). Repulsion due to interaction
between the electron clouds of each atom or molecule then super-
biomolecule and water. It also minimizes energetically unfa- venes. While individual van der Waals interactions are extremely
vorable contacts between water and hydrophobic groups. weak, their cumulative effect is nevertheless substantial for mac-
romolecules such as DNA and proteins which have many atoms in
Hydrophobic Interactions close contact.
Hydrophobic interaction refers to the tendency of nonpolar com-

pounds to self-associate in an aqueous environment. This self- van der Waals Forces
association is driven neither by mutual attraction nor by what van der Waals forces arise from attractions between transient
are sometimes incorrectly referred to as “hydrophobic bonds.” dipoles generated by the rapid movement of electrons of all
Self-association minimizes the disruption of energetically favor- neutral atoms. Significantly weaker than hydrogen bonds
able interactions between the surrounding water molecules. but potentially extremely numerous, van der Waals forces
While the hydrogens of nonpolar groups such as the decrease as the sixth power of the distance separating atoms
methylene groups of hydrocarbons do not form hydrogen (Figure 2–4). Thus, they act over very short distances, typi-
bonds, they do affect the structure of the water that surrounds cally 2 to 4 Å.
them. Water molecules adjacent to a hydrophobic group are
restricted in the number of orientations (degrees of freedom)
that permit them to participate in the maximum number of Multiple Forces Stabilize Biomolecules
energetically favorable hydrogen bonds. Maximal formation The DNA double helix illustrates the contribution of multiple
of multiple hydrogen bonds, which maximizes enthalpy, can forces to the structure of biomolecules. While each individ-
be maintained only by increasing the order of the adjacent ual DNA strand is held together by covalent bonds, the two
water molecules, with an accompanying decrease in entropy. strands of the helix are held together exclusively by noncova-
It follows from the second law of thermodynamics that the lent interactions such as hydrogen bonds between nucleotide
optimal free energy of a hydrocarbon-water mixture is a func- bases (Watson-Crick base pairing) and van der Waals interac-
tion of both maximal enthalpy (from hydrogen bonding) and tions between the stacked purine and pyrimidine bases. The
highest entropy (maximum degrees of freedom). Thus, non- double helix presents the charged phosphate groups and polar
polar molecules tend to form droplets that minimize exposed hydroxyl groups from the ribose sugars of the DNA backbone
surface area and reduce the number of water molecules whose to water while burying the relatively hydrophobic nucleotide
motional freedom becomes restricted. Similarly, in the aque- bases inside. The extended backbone maximizes the distance
ous environment of the living cell the hydrophobic portions of between negatively charged phosphates, minimizing unfavor-
biopolymers tend to be buried inside the structure of the mol- able electrostatic interactions (see Figure 34–2).
ecule, or within a lipid bilayer, minimizing contact with water.
Electrostatic Interactions WATER IS AN EXCELLENT

Interactions between charged groups help shape biomolecular NUCLEOPHILE
structure. Electrostatic interactions between oppositely charged Metabolic reactions often involve the attack by lone pairs of
groups within or between biomolecules are termed salt bridges. electrons residing on electron-rich molecules termed nucleo-
Salt bridges are comparable in strength to hydrogen bonds but philes upon electron-poor atoms called electrophiles. Nucleo-
act over larger distances. They therefore often facilitate the bind- philes and electrophiles do not necessarily possess a formal
ing of charged molecules and ions to proteins and nucleic acids. negative or positive charge. Water, whose two lone pairs of

sp3 electrons bear a partial negative charge (see Figure 2–1), absence of enzymic catalysis, even reactions that are highly
is an excellent nucleophile. Other nucleophiles of biologic favored thermodynamically do not necessarily take place rap-
importance include the oxygen atoms of phosphates, alcohols, idly. Precise and differential control of enzyme activity and the
and carboxylic acids; the sulfur of thiols; and the nitrogen sequestration of enzymes in specific organelles determine the
atom of amines and of the imidazole ring of histidine. Com- physiologic circumstances under which a given biopolymer
mon electrophiles include the carbonyl carbons in amides, will be synthesized or degraded. The ability of enzyme active
esters, aldehydes, and ketones and the phosphorus atoms of sites to sequester substrates in an environment from which
phosphoesters. water can be excluded facilitates biopolymer synthesis.
Nucleophilic attack by water typically results in the cleavage
of the amide, glycoside, or ester bonds that hold biopolymers Water Molecules Exhibit a Slight but
together. This process is termed hydrolysis. Conversely, when
monomer units are joined together to form biopolymers, such Important Tendency to Dissociate
as proteins or glycogen, water is a product, for example, during The ability of water to ionize, while slight, is of central impor-
the formation of a peptide bond between two amino acids. tance for life. Since water can act both as an acid and as a base,
While hydrolysis is a thermodynamically favored reac- its ionization may be represented as an intermolecular proton
tion, the amide and phosphoester bonds of polypeptides and transfer that forms a hydronium ion (H3O+) and a hydroxide
oligonucleotides are stable in the aqueous environment of ion (OH−):
the cell. This seemingly paradoxical behavior reflects the fact H2O + H2O ⇄ H3O + OH-
that the thermodynamics that govern the equilibrium point
of a reaction do not determine the rate at which it will pro- The transferred proton is actually associated with a cluster of
ceed toward its equilibrium point. In the cell, protein cata- water molecules. Protons exist in solution not only as H3O+,
lysts called enzymes accelerate the rate of hydrolytic reactions but also as multimers such as H5O2+ and H7O3+. The proton is
when needed. Proteases catalyze the hydrolysis of proteins nevertheless routinely represented as H+, even though it is in
into their component amino acids, while nucleases catalyze fact highly hydrated.
the hydrolysis of the phosphoester bonds in DNA and RNA. Since hydronium and hydroxide ions continuously recom-
Careful control of the activities of these enzymes is required to bine to form water molecules, an individual hydrogen or oxy-
ensure that they act only at appropriate times. gen cannot be stated to be present as an ion or as part of a water
molecule. At one instant it is an ion; an instant later it is part
of a water molecule. Individual ions or molecules are therefore
Many Metabolic Reactions Involve not considered. We refer instead to the probability that at any
Group Transfer instant in time a given hydrogen will be present as an ion or as
Many of the enzymic reactions responsible for synthesis and part of a water molecule. Since 1 g of water contains 3.46 × 1022
breakdown of biomolecules involve the transfer of a chemical molecules, the ionization of water can be described statistically.
group G from a donor D to an acceptor A to form an acceptor To state that the probability that a hydrogen exists as an ion
group complex, A—G: is 0.01 means that at any given moment in time, a hydrogen
atom has 1 chance in 100 of being an ion and 99 chances out
D—G + A ⇄ A—G + D
of 100 of being part of a water molecule. The actual probability
The hydrolysis and phosphorolysis of glycogen, for example, of a hydrogen atom in pure water existing as a hydrogen ion
involve the transfer of glucosyl groups to water or to ortho- is approximately 1.8 × 10−9. The probability of its being part
phosphate. The equilibrium constant for the hydrolysis of of a water molecule thus is almost unity. Stated another way,
covalent bonds strongly favors the formation of split products. for every hydrogen ion or hydroxide ion in pure water, there
Conversely, many group transfer reactions responsible for the are 0.56 billion or 0.56 × 109 water molecules. Hydrogen ions
biosynthesis of macromolecules involve the thermodynami- and hydroxide ions nevertheless contribute significantly to the
cally unfavored formation of covalent bonds. Enzyme catalysts properties of water.
play a critical role in surmounting these barriers by virtue of For dissociation of water,
their capacity to directly link two normally separate reactions
together. By linking an energetically unfavorable group trans- [H+ ][OH− ]
K=
fer reaction with a thermodynamically favorable reaction, [H2O]
such as the hydrolysis of ATP, a new coupled reaction can be
generated whose net overall change in free energy favors bio- where the brackets represent molar concentrations (strictly
polymer synthesis. speaking, molar activities) and K is the dissociation constant.
Given the nucleophilic character of water and its high con- Since 1 mole (mol) of water weighs 18 g, 1 liter (L) (1000 g)
centration in cells, why are biopolymers such as proteins and of water contains 1000 ÷ 18 = 55.56 mol. Pure water thus
DNA relatively stable? And how can synthesis of biopolymers is 55.56 molar. Since the probability that a hydrogen in pure
occur in an aqueous environment that favors hydrolysis? Cen- water will exist as a hydrogen ion is 1.8 × 10−9, the molar con-
tral to both questions are the properties of enzymes. In the centration of H+ ions (or of OH− ions) in pure water is the

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product of the probability, 1.8 × 10−9, times the molar concen- Low pH values correspond to high concentrations of H+
tration of water, 55.56 mol/L. The result is 1.0 × 10−7 mol/L. and high pH values correspond to low concentrations of H+.
We can now calculate the dissociation constant K for pure Acids are proton donors and bases are proton accep-
water: tors. Strong acids (eg, HCl, H2SO4) completely dissociate into
[H+ ][OH− ] [10−7 ][10−7 ] anions and protons even in strongly acidic solutions (low pH).
K= = Weak acids dissociate only partially in acidic solutions. Simi-
[H2O] [55.56]
larly, strong bases (eg, KOH, NaOH), but not weak bases like
= 0.018 × 10−14 = 1.8 × 10−16 mol/L Ca(OH)2, are completely dissociated even at high pH. Many
biochemicals are weak acids. Exceptions include phosphory-
The molar concentration of water, 55.56 mol/L, is too great to
lated intermediates, whose phosphoryl group contains two
be significantly affected by dissociation. It is therefore consid-
dissociable protons, the first of which is strongly acidic.
ered to be essentially constant. This constant may therefore
The following examples illustrate how to calculate the pH
be incorporated into the dissociation constant K to provide a
of acidic and basic solutions.
useful new constant Kw termed the ion product for water. The
relationship between Kw and K is shown below: Example 1: What is the pH of a solution whose hydrogen
ion concentration is 3.2 × 10−4 mol/L?
[H+ ][OH− ]
K= = 1.8 × 10−16 mol/L pH = − log[H+ ]
[H2O]
K w = ( K )[H2O] = [H+ ][OH− ] = − log(3.2 × 10−4 )
= (1.8 × 10−16 mol/L)(55.56mol/L) = − log(3.2) − log(10−4 )

= −0.5 + 4.0
= 1.00 × 10−14 (mol/L)2
= 3.5
Note that the dimensions of K are moles per liter and those of
Kw are moles2 per liter2. As its name suggests, the ion product Example 2: What is the pH of a solution whose hydroxide
Kw is numerically equal to the product of the molar concentra- ion concentration is 4.0 × 10−4 mol/L? We first define a quan-
tions of H+ and OH−: tity pOH that is equal to −log[OH−] and that may be derived
from the definition of Kw:
K w = [H+ ][OH− ]
At 25°C, Kw = (10−7)2, or 10−14 (mol/L)2. At temperatures K w = [H+ ][OH− ] = 10−14
below 25°C, Kw is somewhat less than 10−14, and at tempera- Therefore,
tures above 25°C it is somewhat greater than 10−14. Within the log[H+ ] + log[OH− ] = log10−14
stated limitations of temperature, Kw equals 10−14 (mol/L)2 for
all aqueous solutions, even solutions of acids or bases. We use or
Kw to calculate the pH of acidic and basic solutions. pH + pOH = 14
To solve the problem by this approach:

pH IS THE NEGATIVE LOG OF THE
[OH− ] = 4.0 × 10−4
HYDROGEN ION CONCENTRATION
The term pH was introduced in 1909 by Sörensen, who defined pOH = − log[OH− ]
it as the negative log of the hydrogen ion concentration: = − log(4.0 × 10−4 )
pH = − log[H+ ] = − log(4.0) − log(10−4 )
This definition, while not rigorous, suffices for many bio- = −0.60 + 4.0
chemical purposes. To calculate the pH of a solution: = 3.4
1. Calculate the hydrogen ion concentration [H+]. Now
pH = 14 − pOH = 14 − 3.4
2. Calculate the base 10 logarithm of [H ]. +
= 10.6
3. pH is the negative of the value found in step 2.
The examples above illustrate how the logarithmic pH scale
For example, for pure water at 25°C, facilitates recording and comparing hydrogen ion concentra-
pH = − log[H+ ] = − log10−7 = −(−7) = 7.0 tions that differ by orders of magnitude from one another,
0.00032 M (pH 3.5) and 0.000000000025 M (pH 10.6).
This value is also known as the power (English), puissant Example 3: What are the pH values of (a) 2.0 × 10−2 mol/L
(French), or potennz (German) of the exponent, hence the use KOH and of (b) 2.0 × 10−6 mol/L KOH? The OH− arises from two
of the term “p.” sources, KOH and water. Since pH is determined by the total [H+]

(and pOH by the total [OH−]), both sources must be considered. Since the numeric values of Ka for weak acids are negative
In the first case (a), the contribution of water to the total [OH−] is exponential numbers, we express Ka as pKa, where
negligible. The same cannot be said for the second case (b):
pK a = − log K a
Concentration (mol/L) Note that pKa is related to Ka as pH is to [H+]. The stronger the
acid, the lower is its pKa value.
(a) (b)
Representative weak acids (left), their conjugate bases
Molarity of KOH 2.0 × 10 −2
2.0 × 10−6 (center), and pKa values (right) include the following:
[OH−] from KOH 2.0 × 10−2 2.0 × 10−6
R—CH2 —COOH R—CH2 COO− pK a = 4 − 5
[OH−] from water 1.0 × 10−7 1.0 × 10−7
+
R—CH2 —NH3 R—CH2 —NH2 pK a = 9 − 10
Total [OH−] 2.00001 × 10−2 2.1 × 10−6
H2 CO3 HCO3− pK a = 6.4
− −2
Once a decision has been reached about the significance of the H2 PO4 HPO4 pK a = 7.2
contribution of water, pH may be calculated as above.
The above examples assume that the strong base KOH
pKa is used to express the relative strengths of both acids and
is completely dissociated in solution and that the concentra-
bases. For any weak acid, its conjugate is a strong base. Simi-
tion of OH− ions was thus equal to that due to the KOH plus
larly, the conjugate of a strong base is a weak acid. The relative
that present initially in the water. This assumption is valid
strengths of bases are expressed in terms of the pKa of their
for dilute solutions of strong bases or acids, but not for weak
conjugate acids. For polyprotic compounds containing more
bases or acids. Since weak electrolytes dissociate only slightly
than one dissociable proton, a numerical subscript is assigned
in solution, we must use the dissociation constant to calcu-
to each dissociation, numbered starting from unity in decreas-
late the concentration of [H+] (or [OH−]) produced by a given
ing order of relative acidity. For a dissociation of the type
molarity of a weak acid (or base) before calculating total [H+]
(or total [OH−]) and subsequently pH. R—NH3+ → R—NH2 + H+
Functional Groups That Are Weak Acids the pKa is the pH at which the concentration of the acid
Have Great Physiologic Significance R—NH3+ equals that of the base R—NH2.
From the above equations that relate Ka to [H+] and to the
Many biochemicals possess functional groups that are weak concentrations of undissociated acid and its conjugate base,
acids or bases. Carboxyl groups, amino groups, and phosphate when
esters, whose second dissociation falls within the physiologic
range, are present in proteins and nucleic acids, most coen- [R—COO− ] = [R—COOH]
zymes, and most intermediary metabolites. Knowledge of the or when
dissociation of weak acids and bases thus is basic to under-
standing the influence of intracellular pH on structure and bio- [R—NH2 ] = [R—NH3+ ]
logic activity. Charge-based separations such as electrophoresis then
and ion exchange chromatography are also best understood in
terms of the dissociation behavior of functional groups. K a = [H+ ]
We term the protonated species (HA or R—NH3+) the acid Thus, when the associated (protonated) and dissociated (con-
and the unprotonated species (A− or R—NH2) its conjugate jugate base) species are present at equal concentrations, the
base. Similarly, we may refer to a base (A− or R—NH2) and its prevailing hydrogen ion concentration [H+] is numerically
conjugate acid (HA or R—NH3+). equal to the dissociation constant, Ka. If the logarithms of both
We express the relative strengths of weak acids and bases sides of the above equation are taken and both sides are multi-
in terms of their dissociation constants. Shown below are the plied by −1, the expressions would be as follows:
expressions for the dissociation constant (Ka) for two repre-
sentative weak acids, R—COOH and R—NH3+. K a = [H+ ]
R—COOH  R—COO− + H+ − log K a = − log[H+ ]
[R —COO− ][H+ ] Since −log Ka is defined as pKa, and −log [H+] defines pH, the
Ka =
[R—COOH] equation may be rewritten as
R—NH3+  R—NH2 + H+ pK a = pH
+
[R—NH2 ][H ] that is, the pKa of an acid group is the pH at which the
Ka =
[R—NH3+ ] protonated and unprotonated species are present at equal

concentrations. The pKa for an acid may be determined by 1.0 –1.0
meq of alkali added per meq of acid

adding 0.5 equivalent of alkali per equivalent of acid. The
0.8 –0.8
resulting pH will equal the pKa of the acid.
0.6 –0.6
Net charge
The Henderson-Hasselbalch
Equation Describes the Behavior of 0.4 –0.4
Weak Acids & Buffers 0.2 –0.2
The Henderson-Hasselbalch equation is derived below.

0 0
A weak acid, HA, ionizes as follows: 2 3 4 5 6 7 8
pH
HA  H+ + A−
The equilibrium constant for this dissociation is FIGURE 2–5 Titration curve for an acid of the type HA. The
heavy dot in the center of the curve indicates the pKa, 5.0.
[H+ ][A− ]
Ka =
[HA] 2. When the ratio [A−]/[HA] = 100:1,
Cross-multiplication gives
[A− ]
+ −
[H ][A ] = K a[HA] pH = pK a + log
[HA]
Divide both sides by [A−]: pH = pK a + log(100/1) = pK a + 2
[HA] 3. When the ratio [A−]/[HA] = 1:10,

[H+ ] = K a
[A− ]
pH = pK a + log(1/10) = pK a + (−1)
Take the log of both sides:
 [HA]  If the equation is evaluated at ratios of [A−]/[HA] ranging
log[H+ ] = log  K a −  from 103 to 10−3 and the calculated pH values are plotted, the
 [A ] 
resulting graph describes the titration curve for a weak acid
[HA] (Figure 2–5).
= log K a + log −
[A ]
Multiply through by −1: Solutions of Weak Acids & Their Salts

[HA] Buffer Changes in pH
− log[H+ ] = − log K a − log
[A− ] Solutions of weak acids or bases and their conjugates exhibit
buffering, the ability to resist a change in pH following addi-
Substitute pH and pKa for −log [H+] and −log Ka, respectively; tion of strong acid or base. Many metabolic reactions are
then accompanied by the release or uptake of protons. Oxidative
[HA] metabolism produces CO2, the anhydride of carbonic acid,
pH = pK a − log −
[A ] which if not buffered would produce severe acidosis. Bio-
logic maintenance of a constant pH involves buffering by
Inversion of the last term removes the minus sign and gives phosphate, bicarbonate, and proteins, which accept or release
the Henderson-Hasselbalch equation protons to resist a change in pH. For laboratory experiments
using tissue extracts or enzymes, constant pH is maintained
[A − ] by the addition of buffers such as MES ([2-N-morpholino]-
pH = pK a + log
[HA] ethanesulfonic acid, pKa 6.1), inorganic orthophosphate (pKa2
7.2), HEPES (N-hydroxyethylpiperazine-N′-2-ethanesulfonic
The Henderson-Hasselbalch equation has great predictive acid, pKa 6.8), or Tris (tris[hydroxymethyl]aminomethane,
value in protonic equilibria. For example, pKa 8.3). The value of pKa relative to the desired pH is the
1. When an acid is exactly half-neutralized, [A−] = [HA]. major determinant of which buffer is selected.
Under these conditions, Buffering can be observed by using a pH meter while
titrating a weak acid or base (Figure 2–5). We can also calcu-
[A− ] 1  late the pH shift that accompanies addition of acid or base to
pH = pK a + log = pK a + log   = pK a + 0
[HA] 1  a buffered solution. In the example below, the buffered solu-
tion (a weak acid, pKa = 5.0, and its conjugate base) is ini-
Therefore, at half-neutralization, pH = pKa. tially at one of four pH values. We will calculate the pH shift

that results when 0.1 meq of KOH is added to 1 meq of each TABLE 2–2 Relative Strengths of Monoprotic, Diprotic,
solution: and Triprotic Acids
Lactic acid pK = 3.86
Initial pH 5.00 5.37 5.60 5.86
Acetic acid pK = 4.76
[A−]initial 0.50 0.70 0.80 0.88
Ammonium ion pK = 9.25
[HA]initial 0.50 0.30 0.20 0.12
Carbonic acid pK1 = 6.37; pK2 = 10.25
([A−]/[HA])initial 1.00 2.33 4.00 7.33
Succinic acid pK1 = 4.21; pK2 = 5.64
Addition of 0.1 meq of KOH Produces
Glutaric acid pK1 = 4.34; pK2 = 5.41
[A−]final 0.60 0.80 0.90 0.98
Phosphoric acid pK1 = 2.15; pK2 = 6.82; pK3 = 12.38
[HA]final 0.40 0.20 0.10 0.02
Citric acid pK1 = 3.08; pK2 = 4.74; pK3 = 5.40
([A−]/[HA])final 1.50 4.00 9.00 49.0
Note: Tabulated values are the pKa values (-log of the dissociation constant).
log ([A−]/[HA])final 0.18 0.60 0.95 1.69
Final pH 5.18 5.60 5.95 6.69

acid increases, whereas that of an amine decreases because eth-
ΔpH 0.18 0.60 0.95 1.69 anol decreases the ability of water to solvate a charged species.
The pKa values of dissociating groups in the interiors of pro-
Notice that ΔpH, the change in pH per milliequivalent of teins thus are profoundly affected by their local environment,
OH− added, depends on the initial pH. The solution resists including the presence or absence of water.
changes in pH most effectively at pH values close to the pKa. A
solution of a weak acid and its conjugate base buffers most
effectively in the pH range pKa ± 1.0 pH unit.
SUMMARY
■■ Water forms hydrogen-bonded clusters with itself and with
Figure 2–5 also illustrates how the net charge on one mole-
other proton donors or acceptors. Hydrogen bonds account for
cule of the acid varies with pH. A fractional charge of −0.5 does the surface tension, viscosity, liquid state at room temperature,
not mean that an individual molecule bears a fractional charge and solvent power of water.
but that the probability is 0.5 that a given molecule has a unit ■■ Compounds that contain O or N can serve as hydrogen bond
negative charge at any given moment in time. Consideration of donors and/or acceptors.
the net charge on macromolecules as a function of pH provides
■■ Entropic forces dictate that macromolecules expose polar
the basis for separatory techniques such as ion exchange chro-
regions to an aqueous interface and bury nonpolar regions.
matography and electrophoresis (see Chapter 4).
■■ Salt bridges, hydrophobic interactions, and van der Waals
forces participate in maintaining molecular structure.
Acid Strength Depends on ■■ pH is the negative log of [H+]. A low pH characterizes an acidic
Molecular Structure solution, and a high pH denotes a basic solution.
Many acids of biologic interest possess more than one dissoci- ■■ The strength of weak acids is expressed by pKa, the negative
ating group. The presence of local negative charge hinders pro- log of the acid dissociation constant. Strong acids have low pKa
ton release from nearby acidic groups, raising their pKa. This values and weak acids have high pKa values.
is illustrated by the pKa values of the three dissociating groups ■■ Buffers resist a change in pH when protons are produced or
of phosphoric acid and citric acid (Table 2–2). The effect of consumed. Maximum buffering capacity occurs ±1 pH unit
adjacent charge decreases with distance. The second pKa for on either side of pKa. Physiologic buffers include bicarbonate,
succinic acid, which has two methylene groups between its orthophosphate, and proteins.
carboxyl groups, is 5.6, whereas the second pKa for glutaric
acid, which has one additional methylene group, is 5.4.
REFERENCES
Reese KM: Whence came the symbol pH. Chem & Eng News
pKa Values Depend on the 2004;82:64.
Properties of the Medium Segel IM: Biochemical Calculations. Wiley, 1968.
The pKa of a functional group is also profoundly influenced Skinner JL: Following the motions of water molecules in aqueous
solutions. Science 2010;328:985.
by the surrounding medium. The medium may either raise
Stillinger FH: Water revisited. Science 1980;209:451.
or lower the pKa relative to its value in water, depending on Suresh SJ, Naik VM: Hydrogen bond thermodynamic properties of
whether the undissociated acid or its conjugate base is the water from dielectric constant data. J Chem Phys 2000;113:9727.
charged species. The effect of dielectric constant on pKa may Wiggins PM: Role of water in some biological processes. Microbiol
be observed by adding ethanol to water. The pKa of a carboxylic Rev 1990;54:432.

3
C H A P T E R
Amino Acids & Peptides

O B J EC T IVES ■■ Diagram the structures and write the three- and one-letter designations for
each of the amino acids present in proteins.
After studying this chapter, ■■ Provide examples of how each type of R group of the protein amino acids
you should be able to: contributes to their chemical properties.
■■ List additional important functions of amino acids and explain how certain
amino acids in plant seeds can severely impact human health.
■■ Name the ionizable groups of the protein amino acids and list their
approximate pKa values as free amino acids in aqueous solution.
■■ Calculate the pH of an unbuffered aqueous solution of a polyfunctional
amino acid and the change in pH that occurs following the addition of a given
quantity of strong acid or alkali.
■■ Define pI and explain its relationship to the net charge on a polyfunctional
electrolyte.
■■ Explain how pH, pKa and pI can be used to predict the mobility of a
polyelectrolyte, such as an amino acid, in a direct-current electrical field.
■■ Describe the directionality, nomenclature, and primary structure of peptides.
■■ Describe the conformational consequences of the partial double-bond
character of the peptide bond and identify the bonds in the peptide backbone
that are free to rotate.
BIOMEDICAL IMPORTANCE acids normally appear in the urine because amino acids are
almost totally reabsorbed in the proximal tubule, conserving
l-α-Amino acids provide the monomer units of the long poly- them for protein synthesis and other vital functions.
peptide chains of proteins. In addition, these amino acids and Certain microorganisms secrete free d-amino acids,
their derivatives participate in cellular functions as diverse or peptides that may contain both d- and l-α-amino acids.
as nerve transmission, and the biosynthesis of porphyrins, Several of these bacterial peptides are of therapeutic value,
purines, pyrimidines, and urea. The neuroendocrine system including the antibiotics bacitracin and gramicidin A, and the
employs short polymers of amino acids called peptides as hor- antitumor agent bleomycin. Certain other microbial peptides
mones, hormone-releasing factors, neuromodulators, and are, however, toxic. The cyanobacterial peptides microcystin
neurotransmitters. Humans and other higher animals can- and nodularin are lethal in large doses, while small quanti-
not synthesize 10 of the l-α-amino acids present in proteins ties promote the formation of hepatic tumors. The ingestion
in amounts adequate to support infant growth or to maintain of certain amino acids present in the seeds of legumes of the
adult health. Consequently, the human diet must contain ade- genus Lathyrus can result in lathyrism, a tragic irreversible
quate quantities of these nutritionally essential amino acids. disease in which individuals lose control of their limbs. Cer-
Each day the kidneys filter over 50 g of free amino acids from tain other plant seed amino acids have also been implicated in
the arterial renal blood. However, only traces of free amino neurodegenerative disease in natives of Guam.
14

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smooth ice, or deep snow; found on all the shores of
Lake Superior, and sometimes at the upper end of
Lake Huron; but most frequent farther north.
Mooze, or Moonce, Ojib. Moose. The nasal sound, at

the end of this word is
common in these dialects;
Moon-swah, Cree but it is difficult to
represent, by the letters of
our alphabet.
I-aw-ba-mooze—Buck moose. No-zha-mooze—Deer

moose. Moonze-aince—Little moose, etc.
A-yance—Opossum, only in the south. The word a-
yance, means crafty.
Shin-goos—Weasel, two kinds.
Shin-goo-sug—Weasels.
Ne-gik—Otter. Ne-gik-wug—Otters.
Kwaush-kwaush-ko-tah-be-ko-sheezh.
Keen-waw-no-wa waw-waw-be-gun-o-je—Long tail
leaping mouse.
Waw-waw-be-gun-o-je—Mouse.
Ah-mik-waw-waw-be-gun-o-je—Beaver, or diving
mouse.
Kah-ge-bin-gwaw-kwa—Shrew. Two species are
common about St. Maries, in winter.
Kahg—Porcupine.[47] Kahg-wug—Porcupines.
Shong-gwa-she—Mink.
Wah-be-zha-she—Marten. Woapchees, Z. p. 18.
A-se-bun—Raccoon.
She-gahg—Skunk.
O-zhusk—Muskrat.
Ah-puk-kwon-ah-je—Bat.
O-jeeg—Fisher weasel, a very stupid animal, easy to
kill.
Ba-bah-mo-ta-jeeg—Reptiles.
Nau-to-way—Thick, short rattle snake. (Sha-no-we-

naw—The rattler?)
She-she-gwa—Common rattle snake. Both these are
occasionally kept tame by the Indians. They
sometimes make feasts to them, and they are said to
be very docile and intelligent.
Me-tik-o-she-she-gwa—Adder.
Na-wa—Moccasin snake.
Pih-kun—Prairie snake. At the head of Mouse River,
and in the prairies towards the Missouri, these snakes
are more than six feet long, and proportionably large.
Pih-kun-un are common snakes, but never half so
large as the above.
Mis-kwan-dib—Red head; copper snake?
O-zha-wus-ko Ke-na-beek—Green snake.
Muk-kud-da Ke-na-beek—Black snake.
O-mus-sun-dum-mo—Water snake.
Wa-in-je-tah Ke-na-beek—Garter snake, (right or
true ge-na-bik.)
O-kaute Ke-na-beek—Lizzard, (legged snake.)
Gee-kut-tau-naung—Lizzard of some kind.
Que-we-zains—Little boy, (also a lizzard.)
Nib-be-ke O-muh-kuk-ke—Oribicular lizzard?
(medicine frog.)
Wain-je-tah O-muh-kuk-ke—Right frogs, or common
frog.
Dain-da—Bull frog, and Hannie, Z. 19.
Mis-ko-muh-kuk-ke—Red toad.[48]
Be-go-muh-kuk-ke—Common toads. These two last,
at the approach of winter, place themselves erect on
the surface of the ground, on their hams, and by
turning themselves round and round, they sink into the
ground, which closes over them, and they keep below
the frost. They are often found, several within two or
three feet of each other, buried deep in the earth, but
keeping constantly their heads erect.
O-shaw-wus-ko-muh-kuk-ke—Tree frog.
Me-zhe-ka, Ottaw.
Large tortoise.
Me-kin-nauk, Ojib.
Ta-ta-be-ko-nauk—Soft shelled tortoise.

Boos-kut-ta-wish—A tortoise with round deep shells.
Mis-kwaw-tais-sa—Terrapin.
Sug-gus-kwaw-ge-ma—Leech.
Be-nais-se-wug—Birds.
Ke-neu—War eagle; the master of all birds.

Me-giz-ze—White headed eagle. Me-giz-ze-wug,
plural.
Ka-kaik—Spotted hawk.
Be-bo-ne-sa, Ottaw.
Winter hawk.
Ke-bu-nuz-ze, Ojib.
No-je-ke-na-beek-we-zis-se—Marsh hawk, (snake

eating.)
Wa-be-no-je Ke-na-beek-we-zis-se—White marsh
hawk.
Mis-ko-na-ne-sa—Red tail hawk.
Pish-ke-neu—Black tail hawk.
Muk-kud-da-ke-neu—Black hawk.
Bub-be-nug-go—Spotted tail hawk.
Be-na-seen’s—Small pheasant hawk.
Cha-een-sa—A small hawk, so named from its cry.
Pe-pe-ge-wiz-zain’s—Smallest hawk.
We-nong-ga—Turkey buzzard.
Kah-gah-ge, Ojib. Raven. Kah-gah-ge-wug—

Gau-gau-ge-she, Ott. Ravens.
On-daig—Crow. On-daig-wug—Crows.
As-sig-ge-nawk—Black bird.
Mis-ko-min-gwe-gun-nah Sig-ge-nauk—Red wing
black bird.
O-pish-kah-gah-ge—Magpie. O-pish-kah-gah-ge-wug
—Magpies.
Gween-gwe-sha—Similar in habits and locality to the
former, and closely resembling, in size and colour, the
following.[49]
Teen-de-se—Blue jay. These begin to lay their eggs
before the snow is off the ground in the spring.
Be-gwuk-ko-kwa o-wais-sa—Thrush.
Ah-luk—Similar to the thrush in habits.
Ween-de-go be-nais-sa—King bird, (the bird that
eats his own kind.)
O-pe-che[50]—Robin.
Ma-mah-twa—Cat bird.
Chaum-ma-wais-she—Another of the same size.
Kos-kos-ko-na-ching—Ground bird? A small bird so
named from its note.
Put-tas-se-wis.
Waw-be-ning-ko-se—Snow birds.
Che-ki-che-gau-na-sa—A very small lively bird,
peculiar to the north.
Mis-kobe-na-sa—Red bird.
Sa-ga-bun-wau-nis-sa—Waxen chatterer.
O-zhah-wus-kobe-na-sa—Green bird.
O-zaw-we-be-na-sa—Yellow bird.
Ma-ma—Red headed wood pecker.
Paw-paw-sa—Spotted wood pecker.
Muk-kud-da paw-paw-sa—Black pawpawsa. The
male of this kind, has a bright yellow spot on the top
of the head. They are found about Lake Superior in
winter.
Mo-ning-gwan-na—Yarril, (highhold.)
Ke-ke-ba-na—small spotted wood pecker.
Che-gaun-do-wais-sa—Brown wood pecker, confined
to cedar countries.
Shin-go-beek-ai-sa—Cedar bird.
Gitche-o-gish-ke-mun-ne-sa—Great king fisher.
O-gish-ke-mun-ne-sa[51]—Common king fisher.
Shaw-shaw-wa-ne-bais-sa—Swallow.
O-ge-bun-ge-gush.
O-kun-is-sa—Loxia enudeator, found at Lake
Superior in February.
Pe, sing. Pe-ug, pl.—A fringilla, smaller than the
waxen chatterer. The female has a spot of red on the
top of the head; the male, the whole head and neck of
the same colour. The tail feathers are bent outwards
near the ends. Found about Lake Superior in the
winter.
Mam-mah-twa.
Bosh-kun-dum-moan—Parakeet, (croch perons.)
Moash-kah-o-se We-kum-mo, (Menomonie)—Stake
driver, (bittern.)
Kun-nuh waw-be-mokee-zhis wais-sa—Fly up the
creek, (sun gazer.)
Me-mom-i-ne-ka-she—Rail, (rice bird.)
Pud-dush-kon-zhe—Snipe.
Gitche-pud-dush-kon-zhe—Wood cock.
Che-chees-che-me-uk—Waders.
Mo-voke—Curliew, (a foreign word.)

Mus-ko-da che-chees-ke-wa—Upland plover.
Wain-je-tah che-chees-ke-wa—Yellow leg plover.
Che-to-waik—Bull head plover.
Che-chees-ke-wais—Tern.
Wawb-uh-che-chawk—White Crane.
O-saw-waw-che-chawk—Sand hill crane.
Me-zis-sa—Turkey.
Be-na—Pheasant.
Mush-ko-da-sa—Grouse; confined to pine and cedar
countries.
Ah-gusk, (Ojib.) Ke-waw-ne, (Ott.)—Prairie hen.
O-me-me—Pigeon; o-me-meeg—pigeons. Amemi, Z.
19.
Ko-ko-ko-oge[52]—Owls.
Waw-wain-je gun-no—Great horned owl.

Wain-je-tah koko-koho—Right owl.
Koko-oanse—Little owl; gokhotit, Z. 18.
Bo-dah-wah doam-ba—Size of a pigeon, (membrum
virile.)
Kaw-kaw-be-sha—Brown owl.
Waw-be-ko-ko—Snow owl, very large.
Waw-o-nais-sa—Whippoorwill.
Baish-kwa—Night hawk.
She-she-bug—Ducks.
Waw-be-zee—Great Swan.
Mah-nah-be-zee—Smaller swan, not common. Their
cry resembles the voice of a man. The word means
ugly or ill looking swan.
Ne-kuh—Brant, ne-kug, pl.
Pish-ne-kuh—A smaller brant.
Wa-wa—Goose; Wa-waig—Geese; Waw-be-wa-wa—
White goose; Waw-be-wa-waig—White geese.
An-ne-nish-sheeb—Duck and mallard.
Tah-gwaw-ge she-sheeb—Fall duck, red neck.
Mah-to-gun she-sheeb—Scrapper bill duck.
Scah-mo—Wood duck.
Wa-weeb-ge-won-ga—Blue wing teal, (swift
winged.)
Ke-nis-te-no-kwa sheeb—Cree woman duck.
Muk-kud-da sheeb—Black duck.
Kitche-waw-we-big-wa-wya—Large blue wing duck.
Pe-gwuk-o-she sheeb—Large bill, or blunt arrow
duck; from pe-gwuk, the blunt or unbarbed arrow. This
species has a large bill, and head of a leaden colour.
They are found throughout the winter, in the rapids
between Lakes Superior and Huron.
Ma-muh-tway-ah-ga—Whistling wing.
Kee-no-gwaw-o-wa sheeb—Long neck duck.
A-ha-wa—House duck.
Wah-ka-we sheeb—White duck.
Gaw-waw-zhe-koos—Shell duck.
Ah-zig-wuk—Fishing duck.
Sah-gah-ta—Mud hen.
Shin-ge-bis—Greebe; Gitche-shin-ge-bis—Large
greebe.
Mahng—Loon.
A-sha-mahng—Small loon.
Gau-gau-geshe sheeb—Cormorant.
Sha-da—Pelican; sha-daig—Pelicans.
Shuh-shuh-gah—Blue Heron.
Gi-aushk-wug—Gulls.
Gitche-gi-aushk—Great gull. Gi-as-koo-sha of the

Ottawwaws.
Paush-kaw gi-aushk—Black headed gull.
Nas-so-waw-gwun-nus-kitte-kwah-gi-aushk—Fork
tailed gull.
Muk-kud-da gi-aushk—Black gull.
Man-e-toanse-sug[53]—Insects.
Bo-dush-kwon-e-she—Large dragon fly.

Bo-dus-kwon-e-sheense—Small dragon fly.
Gitche-me-ze-zauk[54]—Large horse fly.
Me-zauk—Common horse fly.
Me-zauk-oons—Nat fly.
Gitche-ah-mo—Humble bee. Amoe, a bee, Z. 19.
Ah-mo, sing., ah-maag, pl.—Wasps, hornets, etc.
Waw-waw-tais-sa—Lightning bug.
An-ne-me-ke wid-de-koam[55]—Miller, sphinx,
thunder’s louse.
Pah-puk-ke-na—Grasshopper.
Ad-de-sah-wa-a-she—Locust.
Mow-wytch-e-ka-se—Beetle, (dung worker.)
Gitche-o-mis-kose—Great water bugs.
O-mis—Common water bug.
Ma-maing-gwah—Butterfly.
Metig-onishe-moan-ka-she—(He that sleeps in a
stick.) Found in the bottom of springs.
Sha-bo-e-ya-sa—Rowing water bug.
Man-e-toanse o-ke-te-beeg pe-me-but-toan—
Literally, the little (creature or) spirit that runs on the
water.
O-mush-ko-se-se-wug—Grass bugs.
O-o-chug—Blowing flies and house flies.
Sug-ge-ma—Mosquito.
Pin-goosh, pin-goosh-ains-sug—Gnats and sand
flies.
Mat-wa-nuh-kai-moag—Swarming flies.
Sub-be-ka-she—Spider, (net worker.) A-a-be-ko—
Large black spider.
An-e-go—Ant.[56]
Mis-ko-manetoanse—A little red bug common in the
north.
Me-nah-koo-sit manetoanse—Strawberry bug.
Puh-beeg—Flea; Puh-beeg-wug—Fleas.
Eze-gaug—Tick.
E-kwuh—Louse; E-kwug—Lice.
Mo-saig—Worms.
O-zah-wash-ko-mo-sah—Green worm.
Way-muk-kwah-na—Great caterpillar, (bear skin.)
Gitche-mo-sa—Great white grub; gitche-mo-saig,
plural.
Me-shin-no-kau-tait-mo-sa—Millipede.
Pe-mis-koo-de-seence—Snail.
Ke-goi-yug—Fishes.
Nah-ma—Sturgeon.
Mas-ke-no-zha—Maskenonge, or pike.
O-zhaw-wush-ko ke-no-zha—Green pickerel, only
found in the north.
Ke-no-zha—Pickerel; from kenose, long.
Nah-ma-goosh—Trout.
Na-zhum-ma-goosh—Brook trout.
Ne-git-che—Buffalo fish.
Bush-she-to—Sheeps head; bush-she-toag, plural.
Mon-nuh-she-gun—Black bass.
Ad-dik-kum-aig, (attai-kum-meeg, Menom.)—White
fish, or rein-deer fish; from ad-dik, rein-deer, and gum-
maig, water.
Buh-pug-ga-sa—Large sucker.
Mis-kwaw-zhe-gun-no—Red horse.
Nah-ma-bin—Sucker; Mis-kwun nah-ma-bin—Red
sucker.
Ug-gud-dwawsh—Sun fish.
Sah-wa—Perch, (yellow.) Sah-waig, pl.
O-ka-ah-wis—Fresh water herring.
We-be-chee—A flat fish larger than herring; only
found in Red River.
Mon-num-maig—Great cat fish.
Ah-wa-sis-sie—Little catfish. The Indians say this fish
hatches its young in a hole in the mud, and that they
accompany her for some time afterwards.
Ke-na-beek gwum-maig—Eel, (water snake.)
O-da-che-gah-oon—Gar.
Shig-gwum-maig—Shovel nose; only in the
Mississippi.
Kuk-kun-naun-gwi—Little toad fish; Lake Huron.
O-gah-suk—Little dories; Lake Huron.
O-gah—Dory.
Bug-gwut-tum-mo-goon-suk—These are small fishes,
that make their appearance in ponds having no
connection with rivers or lakes, and which are
sometimes quite dry. But though they all perish in
times of drought, they re-appear when the ponds are
filled.
Shaw-ga-she—Craw fish.
Ais—Clam; Ais-sug—Clams.
Ais-ainse—Little clam.
Mis-koan-sug—Red clams.
MINERALS
That the Indians are less observant of inanimate substances than

of organized beings, will be manifest from the following meagre
catalogue of minerals.
Bin-gwaw-beek—Lime stone, (ashes stone.)

Mat-toat-wah-nah-beek—Granite.
Muk-kud-dah-waw-beek—Black stone.
Mik-kwum-me-waw-beek—White Flint, (ice stone.)
Pish-ah-beek—Sulphuret of iron. They often find this
passing into sulphate of iron, and make use of it for
dying black.
O-poih-gun-us-sin—Pipe stone; farther distinguished
according to colour.
O-skaw-shut-waw-beek—Gneiss, (vein stone.)
Mis-kwaw-sin—Red sand stone.
Gaw-gaw-wusk—Gypsum.
Waw-be-gun—White clay.
O-num-un—Ochre.
Mis-kwaw-be-gun—Red earth.
O-saw-waw-be-gun—Yellow earth.
Muk-kud-da-wuk-kum-mik—Black mould.
Waw-be-gun-uk-kaw—Clay ground.
OF TOTEMS
Among the Indians of the Algonkin stock, every man receives from
his father a totem, or family name. They affirm that no man is, by
their customs, allowed to change his totem; and as this distinctive
mark descends to all the children a man may have, as well as to all
the prisoners he may take and adopt, it is manifest that, like the
genealogies of the Hebrews, these totems should afford a complete
enumeration of the stocks from which all the families have been
derived. It differs not from our institution of surnames, except that
the obligations of friendship and hospitality, and the restraint upon
intermarriage, which it imposes, are more scrupulously regarded.
They profess to consider it highly criminal for a man to marry a
woman whose totem is the same as his own; and they relate
instances where young men, for a violation of this rule, have been
put to death by their nearest relatives. They say, also, that those
having the same totem are bound, under whatever circumstances,
as they meet, even though they should be of different and hostile
bands, to treat each other not only as friends, but as brethren,
sisters, and relatives of the same family.
Of the origin of this institution, and of the obligation to its strict
observance, the Indians profess to know nothing. They say they
suppose the totem was given them in the beginning, by their creator.
Like surnames among us, these marks are now numerous; and, as in
the case of our surnames, it is difficult to account for their
multiplicity, without supposing a time when they might have been
changed, or new ones adopted, more easily than at present.
It is not, as yet, well ascertained that any of the North American
Indians, except those of the Algonkin family, have these peculiar
genealogical marks. Those of the great Chippewyan family, in the
north, we are well assured, have them not. From long acquaintance
with the Dahcotah bands of the Mississippi and St. Peters, in which
designation we include the Hoochawgenah, or Winnebagoes, and
the Ioways, and from a more transient sojourning among the Otoes,
the Kansas, the Omawhawes, the Pawnees, and other western
tribes, we have, with careful inquiry and search, been able to collect
no intimation of such a custom among them. But of the western
Indians we cannot speak with entire confidence, as we recollect to
have heard Renville, an interpreter for the Sioux, after much
puzzling and cross-examination, admit that something of the kind
might exist among that people. It may be observed, that the
Algonkins believe all other Indians to have totems, though, from the
necessity they are in general under, of remaining ignorant of those
of hostile bands, the omission of the totem in their picture writing
serves to designate an enemy. Thus, those bands of Ojibbeways who
border on the country of the Dahcotah, or Sioux, always understand
the figure of a man without totem, to mean one of that people.
CATALOGUE OF TOTEMS
Among the Ottawaws and Ojibways with the names of some to whom
they belong.
Muk-kwaw—Bear, the totem of Pe-ga-gun, O-shaw-

wa-no, and O-ka-taw, chiefs of Waw-gun-nuk-kiz-ze.
Ke-no-zha—Pickerel, of A-ke-win-de-ba.
Ad-dik-kun-maig—White fish, of Wawb-o-jeeg, (the
white fisher.)
Moons—Moose, of Naw-o-gee-zhik, (in the middle of
the sky.) This is said to be the original totem of the
Ottawwaws; having received many accessions of
people from other bands, many other totems have
been derived from them, and are now intermixed with
the original stock.
Ad-dik—Rein deer, of Ma-mi-ah-jun, (he that goes.)
Mahng—A loon, of Too-beesh.
Me-giz-ze—White headed eagle, of Me-zhuk-kwun-
na-no.
Ka-kaik—Henhawk, of O-ge-mah-we-nin-ne.
Pe-pe-ge-wiz-zains—Sparrow hawk, of Muk-kud-da-
be-na-sa.
Ah-meek—Beaver, of Wa-me-gon-a-biew and Net-
no-kwa.
Mus-sun-dum-mo—Water snake, of O-kin-je-wun-no,
Sin-ne-way, etc.
——Forked tree, of Keme-wun-O-jeeg, etc.
Gi-oshk—Gull, of Puh-koo-se-gun.
Ad-je-jawk—Crane, of Au-da-mene.
Nah-ma-bin—Sucker, of Nain-noh-we-ton.
Pe-zhew—Wild cat; common totem among the
Muskegoes.
Ah-wa-sis-se—Small cat fish, of Matche-kwe-we-
zainse. Sometimes they call the people of this totem,
“those who carry their young,” from the habits of the
small cat fish.
She-she-gwun—Rattle snake; the totem of Gish-
kaw-ko, Manito-o-geezhik, etc. and by them given to
Tanner.
Many more might be enumerated, but these are sufficient to give

an idea of the kinds of objects from which they choose to derive
their names. The trivial or common name of a man may be, and
often is, changed on his going to war, or at the occurrence of any
remarkable event; but the totem is never changed. It is not true,
that they have, in all instances, the figure of whatever may be their
totem always tattooed on some part of their body, nor that they
carry about them a skin, or any other mark, by which it may be
immediately recognised. Though they may sometimes do this, they
are, in other instances, when they meet as strangers, compelled to
inquire of each other their respective totems.[57]
The word totem is of the Ojibbeway language, and, like almost all
others, is readily moulded into the form of a verb, as will appear
from the following examples:—
Ah-neen en-dah che-un-net, O-to-tem-e-waun maun-duh-pe?
How many are these are totems here?
How many are the totems of this band?
Wa-nain way-gi-osh-kun wa-to-ta-met?
What the gull is his totem?
What is the gull’s totem?
KNOWLEDGE OF ASTRONOMY
Of the opinions of the Indians respecting the heavenly bodies,

little need be said. An extensive acquaintance with the motions,
figures, distances, etc. of these bodies, could not have been
expected from people situated as they are, and deprived altogether
of the aids of instruments, and a written language. They pretend to
no more knowledge on these subjects than they possess.
Au-do-me-ne, an intelligent Ottawwaw of Wawgunuk-kizze, in
answer to my inquiries concerning their opinion of the sun and
moon, related to me the following fable:—
Long ago, an old Ojibbeway chief, and his wife, who lived on the
shore of Lake Huron, had one son, a very beautiful boy. His name
was Ono-wut-to-kwut-to, (he that catches clouds,) and his totem,
after that of his father, a beaver. He would have been a great
favourite with them, for he was, in the main, affectionate and
dutiful, except that they could never persuade him to fast. Though
they gave him charcoal, in place of his usual breakfast, he would
never blacken his face, and if he could find fish eggs, or the head of
a fish, he would roast them, and have something to eat. Once they
took from him what he had thus cooked in place of his accustomed
breakfast, and threw him some coals instead of it. But this was the
last of many attempts to compel him to fast. He took up the coals,
blackened his face, went out, and lay down. At night, he did not
return into the lodge of his parents, but slept without. In his dream
he saw a very beautiful woman come down from above, and stand
at his feet. She said, “Ono-wut-to-kwut-to, I am come for you; see
that you step in my tracks.” The lad obeyed without hesitation, and
stepping carefully in her steps, he presently found himself ascending
above the tops of the trees, through the air, and beyond the clouds.
His guide at length passed through a small round hole, and he
following her, found himself standing on a beautiful and extensive
prairie.
They followed the path, which led them to a large and rich looking
lodge; entering here, they saw on one side pipes and war clubs,
bows, arrows, and spears, with the various implements and
ornaments of men. At the other end of the lodge were the things
belonging to women. Here was the home of the beautiful girl who
had been his companion, and she had, on the sticks, a belt she had
not finished weaving. She said to him, “My brother is coming, and I
must conceal you.” So putting him in one corner, she spread the belt
over him. Ono-wut-to-kwut-to, however, watched what passed
without, from his concealment, and saw the brother of the young
woman come in, most splendidly dressed, and take down a pipe
from the wall. After he had smoked, he laid aside his pipe, and the
sack containing his pah-koo-se-gun, and said, “When, my sister, will
you cease from these practices? Have you forgotten that the
Greatest of the Spirits has forbidden you to steal the children of
those who live below? You suppose you have concealed this that you
have now brought, but do I not know that he is here in the lodge? If
you would not incur my displeasure, you must send him immediately
down to his friends.” But she would not. He then said to the boy,
when he found that his sister was determined not to dismiss him,
“You may as well come out from that place, where you are not
concealed from me, and walk about, for you will be lonesome and
hungry if you remain there.” He took down a bow and arrows, and a
pipe of red stone, richly ornamented, to give him. So the boy came
out from under the belt, and amused himself with the bow and pipe
the man gave him, and he became the husband of the young
woman who had brought him up from the woods near his father’s
lodge.
He went abroad in the open prairie, but in all this fair and ample
country, he found no inhabitants, except his wife and her brother.
The plains were adorned with flowers, and garnished with bright and
sparkling streams, but the animals were not like those he had been
accustomed to see. Night followed day, as on the earth, but with the
first appearance of light, the brother-in-law of Ono-wut-to-kwut-to
began to make his preparations to leave the lodge. All day, and
every day, he was absent, and returned in the evening; his wife,
also, though not so regular in the time of her departure and return,
was often absent great part of the night.
He was curious to know where they spent all the time of their
absence, and he obtained from his brother-in-law permission to
accompany him in one of his daily journeys. They went on in a
smooth and open path, through prairies, to which they could see no
boundary, until Ono-wut-to-kwut-to, becoming hungry, asked his
companion if he did not think he should find any game. “Be patient,
my brother,” said he; “this is my road in which I walk every day, and
at no great distance is the place where I constantly eat my dinner.
When we arrive there you shall see how I am supplied with food.”
They came at length to a place where were many fine mats to sit
down upon, and a hole through which to look down upon the earth.
Ono-wut-to-kwut-to, at the bidding of his companion, looked down
through this hole, and saw far beneath him the great lakes, and the
villages, not of the Ojibbeways only, but of all the red skins. In one
place he saw a war party, stealing silently along toward the hunting
camp of their enemies, and his companion told him what would be
the result of the attack they were about to make. In another place
he saw people feasting and dancing: young men were engaged at
their sports, and here and there women were labouring at their
accustomed avocations.
The companion of Ono-wut-to-kwut-to called his attention to a
group of children playing beside a lodge. “Do you see,” said he, “that
active and beautiful boy?” at the same time throwing a very small
stone, which hit the child, who immediately fell to the ground, and
presently they saw him carried into the lodge. Then they saw people
running about, and heard the she-she-gwun, and the song and
prayer of the medicine man, entreating that the child’s life might be
spared. To this request his companion made answer, “Send me up
the white dog.” Then they could distinguish the hurry and bustle of
preparation for a feast, a white dog killed and singed, and the
people, who were called, assembling at the lodge. While these
things were passing, he addressed himself to Ono-wut-to-kwut-to,
saying, “There are, among you in the lower world, some whom you
call great medicine men; but it is because their ears are open, and
they hear my voice, when I have struck any one, that they are able
to give relief to the sick. They direct the people to send me whatever
I call for, and when they have sent it, I remove my hand from those
I had made sick.” When he had said this, the white dog was
parcelled out in dishes, for those that were at the feast; then the
medicine man, when they were about to begin to eat, said, “We
send thee this, Great Manito;” and immediately they saw the dog,
cooked, and ready to be eaten, rising to them through the air. After
they had dined, they returned home by another path.
In this manner they lived for some time, but Ono-wut-to-kwut-to
had not forgotten his friends, and the many pleasant things he had
left in his father’s village, and he longed to return to the earth. At
last, his wife consented to his request. “Since,” said she, “you are
better pleased with the poverty, the cares, and the miseries of the
world beneath, then with the peaceful and permanent delights of
these prairies, go. I give you permission to depart; not only so, but
since I brought you hither, I shall carry you back to the place where
I found you, near your father’s lodge; but remember, you are still my
husband, and that my power over you is in no manner diminished.
You may return to your relatives, and live to the common age of
man by observing what I now say to you. Beware how you venture
to take a wife among men. Whenever you do so, you shall feel my
displeasure; and if you marry the second time, it is then you will be
called to return to me.”
Then Ono-wut-to-kwut-to awoke, and found himself on the
ground, near the door of his father’s lodge. Instead of the bright
beings of his vision, he saw about him his aged mother, and his
relatives, who told him he had been absent about a year. For some
time he was serious and abstracted; but, by degrees, the impression
of his visit to the upper world wore off. He began to doubt the reality
of what he had heard and seen. At length, forgetful of the
admonitions of his spouse, he married a beautiful young woman of
his own tribe. Four days afterwards she was a corpse. But even the
effect of this fearful admonition was not permanent. He again
ventured to marry, and soon afterwards, going out of his lodge one
night, to listen to some unusual noise, he disappeared, to return no
more. It was believed that his wife from the upper world came to
recall him, according to her threat, and that he still remains in those
upper regions, and has taken the place of his brother-in-law, in
overlooking the affairs of men.
It appears from this tradition, that worship, or sacrifices, are,
among the Ottawwaws, sometimes made to the sun and moon; and
they acknowledge that these luminaries, or rather the man in the
sun, and the woman in the moon, keep watch over all our actions.
The various changes of the moon afford them a method of
measuring time, very definite as to the periods, but variable in the
names they give them. Their old men have many disputes about the
number of moons in each year, and they give different names to
each of these. Some of the names in common use are the following.
The first words are in the Ottawwaw, and the second in the
Menomonie dialect.
O-tu-hu-mene kee-zis—O-tai-hai-min ka-zho—

Strawberry moon.
Me-nes kee-zis—Main ka-zho—Whortleberry moon.
Menomonie-ka-we kee-zis—Pohia-kun ka-zho—Wild
rice gathering moon.
Be-nah-kwaw-we kee-zis—Paw-we-pe-muk ka-zho—
Leaves falling moon.
Gush-kut-te-ne kee-zis—Wun-nai ka-zho—Ice moon.
Ah-gim-me-ka-we kee-zis—Wa-si-ko-si ka-zho—
Snow shoes, Ojib; bright night, Menom.
Mah-ko kee-zis—Wa-mun-nus-so ka-zho—(Manito o-
kee-zis, Ojib.)—Bear moon, Ott.; deer rutting moon,
Men.; (Spirit moon, Ojib.)
Kitche-manito o-kee-zis—Ma-cha-ti-wuk wa-mun-
nuz-so-wuk—Longest moon, good for hunting.[58]
Me-giz-ze-we kee-zis—Na-ma-pin ka-zho—(Na-ma-
bin kee-zis, Ott.)—Sucker moon.
Ne-ke kee-zis—Sho-bo-maw-kun ka-zho—Brant
moon, Ojib.; Sugar moon, Men.
Maung-o kee-zis—As-sa-bun ka-zho—Loon’s moon,
Ojib.; raccoon moon, Men.
Sah-ge-bug-ah-we kee-zis—Pe-ke-pe-muk ka-zho—
Leaves moon.
Another moon spoken of by the Menomonies, is Wai-to-ke Ka-zho,

the snake moon, which belongs to the spring season.
The following short catalogue of stars and constellations, will show
that they pay some attention to the more remote of the heavenly
bodies. Some few of their old men, it is said, have many more
names.
Waw-bun-an-nung—The morning star.

Ke-wa-din-an-nung—The north star.
Muk-koo-ste-gwon—The bear’s head. Three stars in
the triangle.
Muh-koo-zhe-gwun—Bear’s rump. Seven stars.
Oj-eegan-nung-wug—Fisher stars. The bright stars
in ursa major, and one beyond, which forms the point
of the fisher’s nose.
Mah-to-te-sun—The sweating lodge. One of the
poles of this lodge is removed. They say the man
whom they point out near by, was so overcome with
the heat of the Mah-to-te-sun, that in his hurried
attempt to escape, he pulled up this pole.
Mahng—A loon.
Nau-ge-maun-gwait—Man in a canoe hunting the
loon.
Ah-wah-to-wuh o-moag—The companions sailing.
An-nung-o-skun-na—Comet. They have the opinion
common among ignorant white people, that the
appearance of a comet is an indication that war is to
follow. The Ojibbeway An-nung-o-skun-na, seems to
signify blazing star. The Menomonies call them Sko-tie-
nah-mo-kin, the seeing fire. Some of the Ojibbeways,
also, Wa-ween-e-zis-e-mah-guk Ish-koo-da, fire that
has hair.
Of the true cause of the increase and decrease of the moon, of

eclipses, and of other phenomena which depend upon the motions
of the heavenly bodies, they have no correct conceptions. When the
moon is in eclipse, they say it is dying, and they load and discharge
their guns at it; and when they perceive the bright part becoming a
little larger, they imagine they have aided to drive away the sickness
which was overpowering it. Of the milky way, they sometimes say,
that a turtle has been swimming along the bottom of the sky, and
disturbed the mud. Of the aurora borealis, which they call the dance
of the dead, their opinion, though a little more poetic, is equally
childish. Several meteoric phenomena they distinguish from those
remoter appearances which are beyond our atmosphere, and of the
former they sometimes say, “they belong to us.”
What was long ago stated by Roger Williams, of the mythology of
the Indians of Rhode Island, agrees but in part with the opinions of
the present day among the Ottawwaws. Of Cau-tan-to-wit, “the
great south-west god,” we hear nothing. Ning-gah-be-an-nong
Manito, the western god, the younger brother of Na-na-bon-jou, the
god of the country of the dead, has taken his place. In his Saw-waw-
nand, we recognize the Shaw-wun-noug Manito, the southern god of
the Ottawwaws. But all these, Waw-bun-ong Manito, the god of the
morning, or of the east, Ke-way-tin-ong Manito, the god of the
north, with Ka-no-waw-bum-min-uk, “he that sees us,” whose place
is in the sun, are inferior in power to many others; even to the Ke-
zhe-ko-we-nin-ne-wug, the sky people; a race of small, but
benevolent and watchful beings, who are ever ready to do good to
mankind.
CHAPTER II.
Comparison of numerals, to ten, in several American
dialects.
1. Oto—From Say.
Yon-ka
No-wa
Tah-ne
To-wa
Sah-tah
Sha-gua
Shah-a-muh
Kra-rah-ba-na
Shan-ka
Kra-ba-nuh
2. Konza.
Meakh-che
Nom-pah
Yah-ber-re
To-pah
Sha-tah
Shahp-peh
Pa-om-bah
Pa-yah-ber-re
Shank-kuh
Ker-ab-bu-rah
3. Omawhaw.
Meach-che
Nom-bah
Ra-bene
To-bah
Sah-tah
Shap-pa
Pa-noom-ba
Pa-rah-bene
Shoon-kah
Kra-ba-rah
4. Yauktong.
Wan-chah
No-pah
Yah-me-ne
To-pah
Zah-pe-tah
Shah-kah-pe
Shah-ko-e
Sha-kun-do-ah
Nuh-pet-che-wun-bah
Week-che-min-nuh
5. Dahkotah—Of Upper Mississippi.
Wau-zhe-tah
No-a-pah
Yah-min-ne
To-a-pah
Zah-pe-tah
Sha-kah-pe
Shah-koan
Shah-han-doah
Neep-chew-wun-kah
Week-chim-mah-ne
6. Minnetahse.
Le-mois-so
No-o-pah
Nah-me
To-pah
Cheh-hoh
A-cah-me
Chap-po
No-pup-pe
No-was-sap-pa
Pe-sah-gas
7. Pawnee.
As-ko
Pet-ko
Tou-wet
Shke-tiksh
She-oksh
Shek-shah-bish
Pet-ko-shek-sha-bish
Tou-wet-sha-bish
Tok-shere-wa
Tok-shere
8. Choktaw.
Chaf-fah
To-ko-lo
To-cha-nah
Osh-tah
Tath-lah-pe
Han-nah-la
Oon-to-ko-lo
Oon-to-che-nah
Chak-ah-ta
Po-ko-la
9. Ojibbeway.
Ning-gooj-waw, or Ba-zhik
Neezh-waw, or Neezh
Nis-swaw, or Nis-swe
Ne-win
Nah-nun
Ning-good-waw-swe
Neezh-zhwaw-swe
Shwaw-swe
Shong-gus-swe, or shong
Me-dos-swe, or kwaitch
10. Muskwake.
Ne kot
Neesh
Ne-on-en
Ne-kot-waus-keek
Ne-kot-wau-swa
Nee-swa
Ne-o
Neesh-waus-eek
Shaunk
Me-to-swa
11. Minsi—From Heckewelder.
Gut-ti
Nis-cha
Na-cha
Ne-wa
Na-lan
Gut-tasch
Nis-choasch
Cha-asch
No-we-li
Wim-bat
12. Algonkin—From Heckewelder.
Pe-gik
Ninch
Nis-soue
Neou
Na-sau
Nin-gon-ton-as-sou
Nin-chou-as-sou
Nis-sou-as-sou
Chan-gas-sou
Mil-las-sou
13. Delaware—From Heckewelder.
Ni-gut-ti
Nis-cha
Na-cha
Ne-wo
Pa-le-nach
Gut-tasch
Nis-chash
Chasch
Pes-chonk
Tel-len

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Harper’s Illustrated Biochemistry Victor W.

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Victor W. Rodwell, PhD Peter J. Kennelly, PhD

David A. Bender, PhD

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eBook conversion by codeMantra

Peter A. Mayes, PhD, DSc Joe Varghese, MBBS, MD

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I Proteins & Enzymes 1 Peter J. Kennelly, PhD

1 Biochemistry & Medicine 1 S E C T I O N

11 Bioenergetics: The Role of ATP 105

7 Enzymes: Mechanism of Action 56 15 Carbohydrates of Physiological

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V Metabolism of Lipids 195

21 Lipids of Physiologic Significance 195

27 Biosynthesis of the Nutritionally Nonessential 39 Molecular Genetics, Recombinant DNA, &

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VIII Extracellular & Intracellular

49 Intracellular Traffic & Sorting of Proteins 573

42 Hormone Action & Signal

53 Red Blood Cells 646

IX Special Topics (A) 519 54 White Blood Cells 656

43 Nutrition, Digestion, &

44 Micronutrients: Vitamins &

Minerals 527 55 Hemostasis & Thrombosis 669

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Biochemistry & Medicine

O B J EC T IVES ■■ Understand the importance of the ability of cell-free extracts of yeast to

BIOMEDICAL IMPORTANCE DISCOVERY THAT A CELL-FREE

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Genetic Sickle cell Athero- Diabetes

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Transcriptomics Proteomics Glycomics Lipidomics

Stem cell biology

Molecular diagnostics Systems biology Synthetic biology

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FIGURE 2–1 The water molecule has tetrahedral geometry. R R II

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Biomolecules Fold to Position Polar & .50

Interaction energy (kcaI mol–1)

Hydrophobic interaction refers to the tendency of nonpolar com-

Electrostatic Interactions WATER IS AN EXCELLENT

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= (1.8 × 10−16 mol/L)(55.56mol/L) = − log(3.2) − log(10−4 )