Unit8 CarbohydrateMetabolism

Chapter 24
Carbohydrate
Metabolism
Chapter 24
Table of Contents
24.1 Digestion and Absorption of Carbohydrates

24.2 Hormonal Control of Carbohydrate Metabolism
24.3 Glycogen Synthesis and Degradation
24.4 Gluconeogenesis
24.5 The Pentose Phosphate Pathway
24.6 Glycolysis
24.7 Terminology for Glucose Metabolic Pathways
24.8 The Citric Acid Cycle
24.9 The Electron Transport Chain
24.10 Oxidative Phosphorylation
24.11 ATP Production for the Complete Oxidation of Glucose
24.12 Importance of ATP
24.13 Non-ETC Oxygen-Consuming Reactions
24.14 B-Vitamins and Carbohydrate Metabolism
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Section 24.1
Digestion and Absorption of Carbohydrates

Section 24.1
• Carbohydrate digestion: Begins in the mouth

– Salivary enzyme “α-amylase” catalyzes the hydrolysis of α-
glycosidic linkages of starch and glycogen to produce smaller
polysaccharides and disaccharide – maltose
– Only a small amount of carbohydrate digestion occurs in the
mouth because food is swallowed so quickly into the stomach
• In stomach very little carbohydrate is digested:
– No carbohydrate digestion enzymes present in stomach
– Salivary amylase gets inactivated because of stomach acidity

Section 24.1
• The primary site for the carbohydrate digestion is within

the small intestine
– Pancreatic α-amylase breaks down polysaccharide chains into
disaccharide – maltose
• The final step in carbohydrate digestion occurs on the
outer membranes of intestinal mucosal cells
– Maltase – hydrolyses maltose to glucose
– Sucrase – hydrolyses sucrose to glucose and fructose
– Lactase – hydrolyses lactose to glucose and galactose
• Glucose, galactose, and fructose are absorbed into the
bloodstream through the intestinal wall.
• Galactose and Fructose are converted to products of
glucose metabolism in the liver.
Section 24.1
• Following absorption the monosaccharides are carried by the

portal vein to the liver where galactose and fructose are
enzymatically converted to glucose intermediates that enter
into the glycolysis pathway
• The glucose may then pass into the general circulatory
system to be transported to the tissues or converted to
glycogen reserve in the liver.
• The glucose in the tissues may be
a) oxidized to CO2 and H2O (ATP)
b) converted to fat
c) converted to muscle glycogen

Section 23.1
Metabolism
• Blood-sugar level:
– the proper functions of the body are dependent on precise control of the glucose
concentration in the blood.
– the normal fasting level of glucose in the blood is 70-90 mg/100 ml.
• Abnormal conditions:
• A. hypoglycemia
– condition resulting from a lower than the normal blood-sugar level (below 70 mg/100 ml)
– extreme hypoglycemia, usually due to the presence of excessive amounts of insulin, is
characterized by general weakness, trembling, drowsiness, headache, profuse perspiration,
rapid heart beat, lowered blood pressure and possible loss of consciousness.
– Loss of consciousness is most likely due to the lack of glucose in the brain tissue, which is
dependent upon this sugar for its energy.
• B. hyperglycemia
– higher than the normal level (above 120 mg/100 mL); when the pancreas does not secrete
enough insulin
– may temporarily exist as a result of eating a meal rich in carbohydrates.
– extreme hyperglycemia, the renal threshold (160-170 mg/100 mL) is reached and excess
glucose is excreted in the urine

Section 24.9
Hormonal Control of Carbohydrate Metabolism
• Besides enzyme inhibition, carbohydrate metabolism may be

regulated by hormones
• Three major hormones control carbohydrate metabolism:
– Insulin ; Glucagon ; Epinephrine
• Insulin
• 51 amino acid polypeptide secreted by the pancreas
• Promotes utilization of glucose by cells
• The release of insulin is triggered by high blood-glucose levels
• Its function is to lower blood glucose levels by enhancing the formation of
glycogen from glucose (glycogen synthesis)
• The mechanism for insulin action involves insulin binding to proteins
receptors on the outer surfaces of cells which facilitates entry of the glucose
into the cells

Section 24.9
Hormonal Control of Carbohydrate Metabolism
Glucagon
• 29 amino acid peptide hormone produced in the pancreas
• Released when blood glucose levels are low
• Principal function is to increase blood-glucose concentration by
speeding up the conversion of glycogen to glucose (glycogenolysis)
in the liver
• Glucagon elicits the opposite effects of insulin
Epinephrine (also called adrenaline)

• Released by the adrenal glands in response to anger, fear, or excitement
• Function is similar to glucagon, i.e., stimulates glycogenolysis
• Primary target of epinephrine is muscle cells
• Promotes energy generation for quick action

Section 23.1
Metabolism
• There are six major

metabolic pathways
of glucose:
1) Glycogenesis
2) Glycogenolysis
3) Gluconeogenesis
4) Hexose monophosphate
shunt
5) Glycolysis
6) Citric Acid Cycle

Section 24.5
Glycogen Synthesis and Degradation
Glycogenesis and Glycogenolysis

• Involved in the regulation of blood glucose concentration
• When the dietary intake of glucose exceeds immediate needs,
humans and other animals can convert the excess to glycogen,
which is stored in either the liver or muscle tissue.
• Glycogenesis is the pathway that converts glucose into glycogen.
• When there’s need for additional blood glucose, glycogen is
hydrolyzed and released into the bloodstream.
• Glycogenolysis is the pathway that hydrolyzes glycogen to
glucose.

Section 24.6
Gluconeogenesis
• Metabolic pathway by which glucose is synthesized from non-
carbohydrate sources:
– The process is not exact opposite of glycolysis
• Glycogen stores in muscle and liver tissue are depleted with in 12-18 hours
from fasting or in even less time from heavy work or strenuous physical
activity
• Without gluconeogenesis, the brain, which is dependent on glucose as a
fuel would have problems functioning if food intake were restricted for even
one day
• Gluconeogenesis helps to maintain normal blood-glucose levels in times of
inadequate dietary carbohydrate intake
• About 90% of gluconeogenesis takes place in the liver
• Non-carbohydrate starting materials for gluconeogenesis:
– Pyruvate
– Lactate (from muscles and from red blood cells)
– Glycerol (from triacylglycerol hydrolysis)
– Certain amino acids (from dietary protein hydrolysis or from muscle protein
during starvation)
Section 24.8
The Pentose Phosphate Pathway
Hexose monophosphate shunt

• Initial reactant of the pathway is glucose-6-
phosphate
• Also termed phosphogluconate pathway,
because 6–phosphogluconate is one of the
intermediates
• A third name is pentose phosphate pathway,
because ribose-5-phosphate is one of its
products
• The main purposes of the HMP shunt are the
following:
– to produce ribose-5-P for nucleotide
synthesis
– to produce NADPH from NADP+ for fatty
acid and steroid biosynthesis and for
maintaining reduced glutathione (GSH)
inside erythrocytes
– to interconvert pentoses and hexoses

Section 24.2
Glycolysis
• A series of reactions in the

cytoplasm which converts
glucose (C6) to two molecules of
pyruvate (a C3 carboxylate), and
ATP and NADH are produced.
• Also called Embden-Meyerhof
pathway, after the scientist who
elucidated the pathway
• an anaerobic process; each
step takes place without O2; one
of its advantages, the body can
obtain energy from glycolysis
quickly, without waiting for a
supply of O2 to be carried to the
cells.
• occurs in cells lacking
mitochondria, e.g., erythrocytes
and in certain skeletal muscle
cells during intense muscle
activity

Section 24.2
Glycolysis
• Step 1: Formation of glucose-6-phosphate:
– Endothermic reaction catalyzed by
hexokinase
– Energy needed is derived from ATP
hydrolysis
• Step 2: Formation of Fructose-6-phosphate:
– Enzyme: Phosphoglucoisomerase
• Step 3: Formation of Fructose 1,6-bisphosphate:
– Enzyme: phosphofructokinase
• Step 4: Formation of Triose Phosphates:
– C6 species is split into two C3 species
– Enzyme : Aldolase
• Step 5: Isomerization of Triose Phosphates
– DHAP is isomerized to glyceraldehyde 3-
phosphate
– Enzyme: Triosephosphate isomerase
• Step 6: Formation of 1,3-bisphosphoglycerate
– Glyceraldehyde 3-phosphate is oxidized and
phosphorylated
– Enzyme: Glyceraldehyde-3-phosphate
dehydrogenase

Section 24.2
Glycolysis
• Step 7: Formation of 3-bisphosphoglycerate
– It is an ATP producing step
– Enzyme: phosphoglycerokinase
• Step 8: Formation of 2-phosphoglycerate
– Isomerization of 3-phosphoglycerate to
2-phosphoglycerate
– Enzyme: phosphoglyceromutase
• Step 9: Formation of Phosphoenolpyruvate:
– Enzyme: Enolase
• Step 10: Formation of Pyruvate:
– High energy phosphate is transferred
from phosphoenolpyruvate to ADP
molecule to produce ATP and pyruvate
– Enzyme: Pyruvate kinase
• At this point of carbohydrate metabolism
there are at least 2 directions that the
product pyruvate may take.
• The direction depends primarily upon the
availability of oxygen in the cell:

Section 24.2
Glycolysis

Section 24.2
Glycolysis
• If there is adequate oxygen, an aerobic
pathway is followed and pyruvate
enters the Krebs cycle.
• If there is insufficient oxygen available,
the anaerobic pathway is continued
and pyruvate undergoes a series of
reactions to produce lactic acid.
• Lactic acid then is the end-product of
glycolysis, and if there were not some
mechanism for its removal, it would
accumulate in the muscle cells & cause
muscle “crumps”.
• Bacteria also use lactate fermentation
in the production of yogurt and cheese
• Reactions 1  9 are identical for
glycolysis and alocoholic fermentation
• for pyruvic acid, the crossroads
compound, its metabolic fate depends
upon the conditions (aerobic or
anaerobic) and upon the organism
under consideration.

Section 24.2
Glycolysis

Section 24.6
Gluconeogenesis
The Cori cycle. Lactate, formed from
glucose under anaerobic conditions in
muscle cells (glycolysis), is transferred
to the liver, where it is reconverted to
glucose (gluconeogenesis), which is
then transferred back to the muscle
cells.

Section 24.7
Terminology For Glucose Metabolic Pathways
Relationships Among Four Common Metabolic Pathways That
Involve Glucose

Section 24.2
Glycolysis
ATP Production and Consumption

• There is a net gain of two ATP molecules in glycolysis for every
glucose molecule processed
• Overall equation for glycolysis

G lucose + 2NAD+ 2 Pyr uvate + 2NADH + 2H+ + 2H2O
2ADP + 2Pi 2A T P

Section 23.7
The Citric Acid Cycle
• Citric acid cycle: A series of
biochemical reactions in which the
acetyl portion of acetyl CoA is
oxidized to carbon dioxide and ATP
and the reduced coenzymes FADH2
and NADH are produced
• Takes place in the mitochondria
• Also known as tricarboxylic acid
cycle (TCA) or Krebs cycle:
– Named after Hans Krebs who
elucidated this pathway
• Two important types of reactions:
– Reduction of NAD+ and FAD to
produce NADH and FADH2
– Decarboxylation of citric acid to
produce carbon dioxide
– The citric acid cycle also
produces 2 ATP by substrate
level phosphorylation from GTP

Section 23.7
• Step 1: Formation of Citrate
• Step 2: Formation of
Isocitrate
• Step 3: Oxidation of Isocitrate
and Formation of CO2:
involves oxidation–reduction
as well as decarboxylation
• Step 4: Oxidation of Alpha-
Ketoglutarate and Formation
of CO2
• Step 5: Thioester bond
cleavage in Succinyl CoA
and Phosphorylation of GDP
to form GTP
• Step 6: Oxidation of
Succinate
• Step 7: Hydration of
Fumarate
• Step 8: Oxidation of L-Malate
to regenerate Oxaloacetate

Section 23.7
• Important features of the cycle:
• The reactions of the cycle takes place in the mitochondrial matrix, except the succinate
dehydrogenase reaction that involves FAD. The enzyme that catalyzes this reaction is an
integral part of the inner mitochondrial membrane.
• The “fuel “ for the cycle is acetyl CoA, obtained from the breakdown of carbohydrates, fats,
and proteins.
• Four of the cycle reactions involve oxidation and reduction. The oxidizing agent is either
NAD+ (three times) or FAD (once). The operation of the cycle depends on the availability of
these oxidizing agents.
• In redox reactions, NAD+ is the oxidizing agent when a carbon-oxygen double bond is
formed; FAD is the oxidizing agent when a carbon-carbon double bond is formed.
• The three NADH and the one FADH2 that are formed during the cycle carry electrons and
H+ to the electron transport chain through which ATP is synthesized.
• Two carbon atoms enter the cycle as acetyl unit of the acetyl CoA, and two carbon atoms
leave the cycle as two molecules of CO2. The carbon atoms that enter and leave are not
the same ones. The carbon atoms that leave during one turn of the cycle are carbon atoms
that entered during the previous turn of the cycle.
• Four B vitamins are necessary for the proper functioning of the cycle: riboflavin (in both
FAD and α-ketoglutarate dehydrogenase complex), nicotinamide (in NAD+), pantothenic
acid (in CoASH), and thiamin (in α-ketoglutarate dehydrogenase complex)
• One high-energy GTP molecule is produced by substrate level phosphorylation.
Section 23.7
Regulation of the Citric Acid Cycle

• The rate at which the citric acid cycle operates is controlled by ATP
and NADH levels
• When ATP supply is high, ATP inhibits citrate synthase (Step 1 of
Citric acid cycle)
• When ATP levels are low, ADP activates citrate synthase
• Similarly ADP and NADH control isocitrate dehydrogenase:
– NADH acts as an inhibitor
– ADP as an activator. 26
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Section 23.8
The Electron Transport Chain
• The electron transport chain (ETC) facilitates the passage of

electrons trapped in FADH2 and NADH during citric cycle
• ETC is a series of biochemical reactions in which intermediate
carriers (protein and non-protein) aid the transfer of electrons and
hydrogen ions from NADH and FADH2
• The ultimate receiver of electrons is molecular oxygen
• The electron transport (respiratory chain) gets its name from the fact
that electrons are transported to oxygen absorbed via respiration
• ETC is the sequence of reactions whereby the reduced forms of the
coenzymes are reoxidized, ultimately by O2

Section 23.8
• The enzymes and electron carriers needed for the ETC

are located along inner mitochondrial membrane
• They are organized into four distinct protein complexes
and two mobile carriers
• The four protein complexes tightly bound to membrane:
• Complex 1: NADH-coenzyme Q reductase
• Complex II: Succinate-coenzyme Q reductase
• Complex III: Coenzyme Q - cytochrome C reductase
• Complex IV: Cytochrome C oxidase
• Two mobile electron carriers are:
– Coenzyme Q and cytochrome c.

Section 23.8
Complex I: NADH-
Coenzyme Q Reductase
• Facilitates transfer of
electrons from NADH
to coenzyme Q
Complex II: Succinate-

Coenzyme Q Reductase
• Succinate is converted
to fumarate by this
complex
• In the process it
generates FADH2
• CoQ is the final
recipient of the
electrons from FADH2

Section 23.8
Complex III: Coenzyme Q –
Cytochrome c Reductase
• Several iron-sulfur proteins
and cytochromes are electron
carriers in this complex
• Cytochrome is a heme iron
protein in which reversible
oxidation of an iron atom
occurs
Complex IV: Coenzyme Q –
Cytochrome c Reductase
• The electrons flow from cyt c to
cyt a to cyt a3
• In the final stage of electron
transfer, the electrons from cyt
a3, and hydrogen ion (H+)
combine with oxygen (O2) to
form water
• O2 + 4H+ + 4e-  2 H2O

Section 23.8
• Summary of the flow of electrons through four

complexes of the electron transport chain.

Section 23.9
Oxidative Phosphorylation
• Oxidative phosphorylation – process by which ATP

is synthesized from ADP and Pi using the energy
released in the electron transport chain by coupled
reactions
• Coupled Reactions -- are pairs of biochemical
reactions that occur concurrently in which energy
released by one reaction is used in the other
reaction
– example: oxidative phosphorylation and the
oxidation reactions of the electron transport
chain are coupled systems

Section 23.9
• The coupling of ATP synthesis with the reactions of the ETC is related to the
movement of protons (H+ ions) across the inner mitochondrial membrane
• Complexes I, III and IV of ETC chain also serve as “proton pumps” to transfer
protons from the matrix side of the inner membrane to the intermembrane space
• For every two electrons passed through ETC, four protons cross the inner
mitochondrial membrane through complex I, four through complex III and two more
though complex IV
• This proton flow causes a buildup of H+ in the intermembrane space
• The high [H+] in the intermembrane space becomes the basis for ATP synthesis

Section 23.9
• The resulting concentration
difference (high in
intermembrane space than in
matrix) constitutes an
electrochemical (proton)
gradient which is always
associated with potential energy
• The gradient build-up would
spontaneously push the H+ ions
through membrane-bound ATP
synthase
• Proton flow is not through the
membrane itself since it is not
permeable to H+ ions
• The proton flow through the
ATP synthetases powers the
synthesis of ATP
• ATP synthetases are the
coupling factors in the ETC/OP
coupled reactions

Section 23.10
ATP Production for the Common Metabolic Pathway
• Formation of ATP accompanies
the flow of protons from the
intermembrane space back into
the mitochondrial matrix.
• The proton flow results from an
electrochemical gradient across
the inner mitochondrial
membrane
• For each mole of NADH
oxidized in the ETC, 2.5 moles
of ATP are formed.
• For each mole of FADH2
Oxidized in the ETC, only 1.5
moles of ATP are formed.
• For each mole of GTP
hydrolyzed one mole of ATP
are formed.
• Ten molecules of ATP are
produced for each acetyl CoA
catabolized in the TCA

Section 23.9
Summary of the Common Metabolic Pathway

Section 24.4
ATP Production for the Complete Oxidation of Glucose

Section 24.4
• Cytosolic NADH produced
during Step 6 of Glycolysis
cannot directly participate in
the electron transport chain
because mitochondria are
impermeable to NADH and
NAD+
• Glycerol 3-phosphate-
dihydroxyacetone phosphate
transport system shuttles
electrons from NADH, but
not NADH itself, across the
membrane:
– Dihydroxyacetone
phosphate and glycerol
phosphate freely cross
the mitochondrial
membrane
– The interconversion
shuttles the electrons
from NADH to FADH2

Section 24.4
• A total of 30 ATP molecules are produced in muscle and

nerve cells:
– 26 from oxidative phosphorylation / electron transport
chain coupled reactions
– 2 from oxidation of glucose to pyruvate
– 2 from conversion of GTP to ATP
• Aerobic oxidation of glucose is 15 times more efficient in
the ATP production as compared to anaerobic lactate
and ethanol processes
• In other cells such as heart and liver cells a more
complex shuttle system is used and 32 molecules are
produced instead of 30 per glucose molecule

Section 23.11
The Importance of ATP
• The cycling of ATP and ADP in metabolic processes is

the principal medium for energy exchange in biochemical
processes

Section 23.12
Non-ETC Oxygen-Consuming Reactions
• >90% of inhaled oxygen via respiration is consumed

during oxidative phosphorylation.
• Remaining O2 are converted to several highly reactive
oxygen species (ROS) with in the body.
• Examples of ROS:
– Hydrogen peroxide (H2O2)
– Superoxide ion (O2-) and
– Hydroxyl radical (OH)
– Superoxide ion and hydroxyl radicals have unpaired electron
and are extremely reactive
• ROS can also be formed due to external influences such
as polluted air, cigarette smoke, and radiation exposure

Section 23.12
• Reactive oxygen species (ROS) are both beneficial as

well a problematic within the body
• Beneficial Example: White blood cells produce a
significant amount of superoxide free radicals via the
following reaction to destroy the invading bacteria and
viruses.
– 2O2 + NADPH  2O2- + NADP+ + H+

Section 23.12
• > 95% of the ROS formed are quickly converted to non

toxic species :
Superoxide
2O2- + 2H+ dismutase H2O2 + O2
Catalase H2O + O2
2H2O2
• About 5% of ROS escape destruction by superoxide

dismutase and catalase enzymes.

Section 23.12
• Antioxidant molecules present in the body help trap ROS

species
• Antioxidants present in the body:
• Vitamin K
• Vitamin C
• Glutathione (GSH)
• Beta-carotene
• Plant products such as flavonoids are also good
antioxidants – Have shown promise in the management
of many disorders associated with ROS production

Section 23.13
B Vitamins and the Common Metabolic Pathway
• Structurally modified B-vitamins function as coenzymes

in the metabolic pathways
• Four B Vitamins participate in various reactions:
– Niacin – NAD+ and NADH
– Riboflavin – as FAD, FADH2 and FMN
– Thiamin – as TPP
– Pantothenic acid - as CoA
• With out these B-vitamins body would be unable to
utilize carbohydrates, proteins and fats as energy
sources.

Section 24.10
B-Vitamins and Carbohydrate Metabolism

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Chapter 24

24.1 Digestion and Absorption of Carbohydrates

Copyright © Cengage Learning. All rights reserved 2

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• Carbohydrate digestion: Begins in the mouth

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• The primary site for the carbohydrate digestion is within

• Following absorption the monosaccharides are carried by the

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• Besides enzyme inhibition, carbohydrate metabolism may be

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Epinephrine (also called adrenaline)

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• There are six major

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Glycogenesis and Glycogenolysis

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Hexose monophosphate shunt

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• A series of reactions in the

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ATP Production and Consumption

• Overall equation for glycolysis

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Regulation of the Citric Acid Cycle

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• The electron transport chain (ETC) facilitates the passage of

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• The enzymes and electron carriers needed for the ETC

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Complex II: Succinate-

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• Summary of the flow of electrons through four

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• Oxidative phosphorylation – process by which ATP

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Summary of the Common Metabolic Pathway

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• A total of 30 ATP molecules are produced in muscle and

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• The cycling of ATP and ADP in metabolic processes is

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• >90% of inhaled oxygen via respiration is consumed