Carbohydrate Metabolism-I

Instructor: Asst. Prof. Dr. Akıle Tuncal

akile.tuncal@kstu.edu.tr
 Carbohydrates
Carbohydrates are the most abundant organic molecules in nature.
Medical and biological importance(functions)
1.Source and storage of energy eg glucose and glycogen.
2. Structural components eg skin,bone, cell..etc
3. Involved in cell-cell interaction.
4. Their derivatives are drugs eg erythromycin.
5.Survival of Antarctic fish in icy environment is due to presence of anti-freeze
glycoproteins in their blood.
6. Ascorbic acid, a derivative of carbohydrate is a water-soluble vitamin.
2
Digestion and Absorption
Digestion of Carbonhydrates
 Digestion of Carbohydrates
• Free monosaccharides are not commonly present in the diet in significant
quantities.

• First of all, carbohydrates must be absorbed from gastrointestinal tract into

blood stream.

• Simple carbohydrates allowed into enterocytes. Poly-, tri- and disaccharides

must be hydrolyzed prior to absorption.

• The hydrolytic enzymes are called glycosidases.

5
 Digestion of Carbohydrates
• Starts in the mouth.

• The key enzyme is salivary α-amylase, a glycosidase that specifically hydrolyzes

α(1-4) glycosidic linkages.

• Be aware of that the β(1-4) bonds of cellulose, the β(1-4) bonds of lactose, and
the α(1-6) linkages that form branch points in the starch amylopectin are resistant
to this enzyme.

• Digestion by salivary amylase continues in the stomach in the food bolus until
gastric acid lowers the pH of the environment.

6
 Digestion of Carbohydrates
• In the mouth: Salivary amylase hydrolyzes starch into dextrin and maltose.
• In the stomach: Salivary amylase is inactive due to low pH.
• In the small intestines: Pancreatic and intestinal enzymes are involved in
the hydrolysis of oligo- and polysaccharides.
α-amylase
(pancreatic)
Dextrins Maltose +Maltotriose (or Isomaltose)

maltase
Maltose 2 Glucose

Lactose lactase Glucose + Galactose

sucrase
Sucrose Glucose + Fructose

7
Non-Ruminant Carbonhydrate Digestion
Carbonhydrate Digestion
Digestion in Small Intestine
Digestion in Small Intestine
Digestion of Disaccarides
Digestion in Large Intestine
Overview Monogastric Carbonhydrate Digestion
Carbonhydrate Absorbtion in Monogastrics
Nutrient Absoption-Carbohydrate
 Absorption, Transport and Distribution
• Glucose and galactose: are absorbed by mucosal cells by active
transport which requires energy and the involvement of a specific
receptor, namely sodium-glucose transporter-1 (SGLT-1).
• 15% of glucose leaks back to intesitinal lumen, 25% diffuses through the
basolateral membrane into the circulation, the major portion is transported
into the circulation by GLUT-2.

• Fructose: is transported into the mucosal cell by a specific facilitative

transporter GLUT-5.
• Transport is independent of glucose concentration.
• Frucotose is transported from the cell by GLUT-2. Only down a concentration
gradient.
 Integrated Metabolism in Tissues

Fate of Absorbed Monosaccharides

• Following the transport across the wall of the intestines, the monosaccharides
enter the portal circulation.

• Absorbed monosaccharides are carried to liver.

• Galatactose and fructose are converted to glucose derivatives in the liver.

• Glucose is also metabolized in the liver. However, it is not completely removed

from the organ.

• The remainder of the glucose passes into the systemic blood supply to feed other
tissues.
Summary of Carbohydrate Digestion and
Absorption in Monogastics
Carbonhydrate Digestion and Absorption
,

Intermediary Metabolism

23
We eat, we digest, we absorb, then what?
Three fates for nutrients
1) Most are used to supply energy for life
2) Some are used to synthesize structural or
functional molecules
3) The rest are stored for future use
What is Metabolism?
Metabolism: total sum of the chemical reactions happening in a
living organism (highly coordinated and purposeful activity)
a. Anabolism pathways- energy requiring biosynthetic
pathways
b. Catabolism pathways - degradation of fuel molecules and
the production of energy for cellular function
c. Amphibolic pathways-acting as links between the anabolic
and catabolic pathways
• Almost all reactions are catalyzed by enzymes
• The primary functions of metabolism are:
a. acquisition & utilization of energy
b. Synthesis of molecules needed for cell structure and
functioning (i.e. proteins, nucleic acids, lipids, & CHO)
c. Removal of waste products
 Integrated Metabolism in Tissues
Overview of glucose metabolism

Figure: The major pathways of glucose utilization.

26
Integrated view of carbohydrate metabolism

27
 The Metabolic Pathways of Carbohydrate Metabolism

Glycogenesis: The synthesis of glycogen

Glycogenolysis: The breakdown of glycogen

Glycolysis: The oxidation of glucose

Gluconeogenesis: The production of glucose from non-carbohydrate intermediates

Pentose phosphate pathway (hexosemonophosphate shunt): The production of five-carbon

monosaccharides and nicotinamide adenine dinucleotide phosphate (NADPH)

Tricarboxylic acid (TCA) cycle: The oxidation of pyruvate and acetyl-CoA to CO2 and H2O
28
The intermediary
metabolism????

29
 Fates of the Body Carbohydrates
• Glucose
– The principal carbohydrate that is utilized by the cell

Carbohydrate metabolism is the story of glucose metabolism

• In the liver fructose and mannose are changed to glucose
• Glucose may undergo one of the following fates:
– Oxidative (catabolic) fates:
• Major pathways: A. Glycolysis** B. Krebs' cycle**
• Minor pathways: A. Pentose shunt B. Uronic acid pathway
– Anabolic fates:

• Gluconeogenesis & Glycogenesis

• Monosaccharides synthesis & Lactose synthesis

• Glycolipids, glycoproteins & Proteoglycans synthesis

22-Mar-23 31
 Cellular Respiration
Occurs in three series of reactions
1. Glycolysis
2. Citric acid cycle
3. Electron transport chain

Produces Read about bioenergetics.

• carbon dioxide
• water
• ATP (chemical energy)
• heat

Includes
• anaerobic reactions (without O2) - produce little ATP
• aerobic reactions (requires O2) - produce most ATP
 ATP Molecules
 each ATP molecule has three parts:
• an adenine molecule
• a ribose molecule
• three phosphate molecules in a chain
• Third phosphate attached by high-energy bond
• when the bond is broken, energy is transferred
• when the bond is broken, ATP becomes ADP
• ADP becomes ATP through phosphorylation
• phosphorylation requires energy released from cellular respiration
 ATP
One of the common links between catabolism and anabolism is ATP.
• ATP is used to shuttle chemical energy from catabolism to anabolism.
Glycolysis
Glycolysis Fig . Gylcolysis
an example of a
metabolic
pathway.

35
Overview of Glycolysis
• Employed by all tissues.
A) Aerobic glycolysis
 Pyruvate is the end product of glycolysis in cells
with mitochondria and an adequate supply of
oxygen.
 Has a series of ten reactions.
 oxygen is required to reoxidize the NADH formed
during the oxidation of glyceraldehyde 3-
phosphate.
 sets the stage for the oxidative decarboxylation of
pyruvate to acetyl CoA,
36
 ,

B) anaerobic glycolysis
it can occur without the participation of oxygen.
pyruvate is reduced to lactate as NADH is oxidized to
NAD+.
Lactate is the end product.
allows the production of ATP in tissues that lack
mitochondria (for example, red blood cells) or in cells
deprived of sufficient oxygen.

37
• Catabolic and anabolic processes in anaerobic carbohydrate
metabolism:

• The gold arrows show the glycolytic pathway and the breakdown
of polysaccharides that supply this pathway.

• Glycolysis generates ATP anaerobically and provides fuel for the

aerobic energy-generating pathways.

• The green arrows show the gluconeogenesis pathway, the

synthesis of polysaccharides such as glycogen.

• The blue arrow shows the pentose phosphate pathway, an

alternative carbohydrate oxidation pathway needed for
nucleotide synthesis.

Copyright © 2013 Pearson Canada Inc.

• The numbers 1, 2, and 3 identify the three stages of metabolism
 2NADH are formed when
pyruvate is produced (aerobic
glycolysis), whereas NADH is
reconverted to NAD+ when
lactate is the end product
(anaerobic glycolysis).

39
• Glycolysis is especially important in:
• RBCs
• Cornea, lens & some parts of retina limited blood
supply & lack of mitochondria
• Kidney (medulla), testicles, leukocytes & white
muscle fibers, relatively few mitochondria & a
limited supply of oxygen
• Contracting muscles decreases oxygen
• Cancer cells
• High rate of glycolysis than normal
cells
• Why? lack of an extensive capillary network
& smaller numbers of mitochondria
• Brain & gastrointestinal tract normally derive
most of their energy
40
 Reactions of Glycolysis
• The conversion of glucose to pyruvate occurs in two stages.

• The first five reactions of glycolysis correspond to an energy

investment phase(steps 1-5) in which the phosphorylated forms
of intermediates are synthesized at the expense of ATP.
• The subsequent reactions of glycolysis constitute an energy
generation phase(steps 6-10) in which a net of two molecules of
ATP are formed by substrate-level phosphorylation per glucose
molecule metabolized.

41
Glycolysis: An Overview
The two phases of glycolysis and the products of glycolysis:

Copyright © 2013 Pearson Canada Inc.

43
Energy investment phase Energy generation phase

3
6

1
7

8
4
2
5 9

10 44
glycolysis
 Glycolysis
Event 1 -
Phosphorylation Event 3 – Production
• two phosphates of NADH and ATP
added to glucose • hydrogen atoms are
• requires ATP released
• hydrogen atoms bind to
NAD+ to produce NADH
• NADH delivers hydrogen
atoms to ETC if oxygen is
available
• ADP is phosphorylated to
become ATP
• two molecules of pyruvic
acid are produced

Event 2 – Splitting (cleavage)

•6-carbon glucose split into two 3-carbon
3/22/2023 45
molecules
 Differences b/n Hexokinase (I-III) & Glucokinase
Hexokinase I–III Glucokinase
Site: Liver parenchymal & pancreatic islet
All tissues except liver cells cells
Substrate: Glucose only
Glucose Fru & Gal It is an inducible enzyme:
Induction:
Affected by Glc & insulin
Non-inducible enzyme,
It has a low affinity
i.e., constitutive
Affinity for glucose:  high Km
High affinity low Km No
Allosteric inhibitor: Activates Glc to remove it from the
Yes Glc-6- phosphate blood
Function: following a meal for storage
Activates Glc for energy
irrespective of its blood [Glc]
47
 Phase I. Energy Investment.
1. Phosphorylation(1st ATP)of Glucose at the expense of an ATP. The first
investment of an ATP here is called “priming.”,
 Enzymes = hexokinase, glucokinase inhibited by its product, glucose
6-phosphate.
2. Isomerization of glucose 6-phosphate
3. Phosphorylation(2nd ATP ) of fructose 6-phosphate
• is the most important control point and the rate-limiting and committed step
of glycolysis
4. Cleavage of fructose 1, 6-bisphosphate
5. Isomerization of dihydroxyacetone phosphate and glyceraldehyde 3-
phosphate- used further in glycolysis.
Finally, two glyceraldehyde 3-phosphate molecules from one glucose molecule
with the expenditure of two ATPs.
Therefore: the product & energy yields of the following steps are multiplied by
two relative to glucose. 48
6. Oxidation of glyceraldehyde 3-phosphate
• formation of NADH and high energy phosphorylated compound, Pi
addition.
7. Synthesis of 3-phosphoglycerate producing ATP(1st)
• first substrate level phosphorylation
• the enzyme is reversible kinase unlike others
8- Phosphate shift setup
9. Dehydration of 2-phosphoglycerate
10.Formation of pyruvate producing ATP(2nd)
NB: steps 1,3 and 10 irreversible but others reversible
NADH at step 6 , ATPs at steps 7 and 10 are produced.
49
 Pyruvate Kinase deficiency

• The normal, mature erythrocyte lacks mitochondria and is,

therefore, completely dependent on glycolysis for production of
ATP.

• ATP required to meet the metabolic needs of the red blood cell,
for the maintenance of the biconcave, flexible shape of the cell.

• The premature death and lysis of red blood cells results in

hemolytic anemia.
50
 Energy yield from glycolysis
1. Anaerobic glycolysis, 2 ATPs are generated for each molecule of
glucose converted to two molecules of lactate ; no net production or
consumption of NADH.

2. Aerobic glycolysis
• a net gain of two ATP per molecule of glucose.
• Two molecules of NADH are also produced per molecule of glucose.
• Ongoing aerobic glycolysis requires the oxidation of most of this
NADH by the electron transport chain, producing approximately
three ATP for each NADH molecule entering the chain .
51
Reactions of Glycolysis
 REGULATION OF GLYCOLYSIS

 hexokinase
 phosphofructokinase
 pyruvate kinase

•Regulated and irreversible

enzymes of glycolysis

53
 Metabolic Fates of Pyruvate
• Pyruvate represents a central metabolic branch point.

• Its fate depends crucially on the oxidation state of the cell,

which is related to the reaction catalyzed by glyceraldehyde-3-
phosphate dehydrogenase (reaction 6).

• Recall that this reaction converts 1 mole of NAD+ per mole of

triose phosphate to NADH.

• The cytoplasm has a finite supply of NAD+ so this NADH must

be reoxidized for glycolysis to continue.
 Metabolic Fates of Pyruvate
• Pyruvate must be reduced to lactate when tissues are
insufficiently aerobic to oxidize all of the NADH formed in
glycolysis.

• Microorganisms can oxidize NADH via fermentations

producing lactate or ethanol.
 Metabolic Fates of Pyruvate
Yeast converts pyruvate to ethanol in a two-step pathway:

• This alcoholic fermentation starts with the nonoxidative

decarboxylation of pyruvate to acetaldehyde, catalyzed by
pyruvate decarboxylase.

• NAD+ is regenerated in the next reaction, the NADH-dependent

reduction of acetaldehyde to ethanol, catalyzed by alcohol
dehydrogenase.
 Metabolic Fates of Pyruvate
• The first reaction requires thiamine pyrophosphate as a coenzyme.

• The vitamin is structurally complex, but its conversion to the coenzyme form,
thiamine pyrophosphate, or TPP, involves simply an ATP-dependent
pyrophosphorylation.

• Thiamine pyrophosphate is the coenzyme for all decarboxylations of a-keto

acids.

• Unlike b-keto acids, a-keto acids cannot stabilize the carbanion transition state
that develops during decarboxylation, and they thus require the aid of a
cofactor (TPP).

• The thiazole ring of TPP is the functional part of the coenzyme, allowing it to
bind and transfer activated aldehydes.
 Energy and Electron Balance Sheets

• Glycolysis, which yields 2 ATP per glucose, is fast but releases only a
small fraction of the energy available from glucose.

• In alcoholic fermentation as in lactate fermentation, an exergonic

process coupled to an endergonic process.
 Energy and Electron Balance Sheets
Energy profile of anaerobic glycolysis:

• Most of the reactions function at or

near equilibrium and are freely
reversible in vivo.

• The three enzymes that catalyze

reactions so highly exergonic as to be
virtually irreversible(arrows) are
subject to allosteric control.
THANK YOU!!!...=)

60