CARBOHYDRATE METABOLISM

OVERVIEW

BIC 203 (LECTURE 01)

C. Z. Uche
Learning Objectives:
By the end of this session you should be able to:
• Outline the two stages of glycolysis.

• Describe the steps of glycolysis between glucose and

pyruvate and recognize all the intermediates and
enzymes and the cofactors that participate in the
reactions.
• Mention ATP-generating reactions.

• Illustrate the regulation of glycolysis.

Carbohydrate Metabolism -Overview
•Glucose is the major fuel of most organisms.
• Major pathways of CHO metabolism either begin or end with
glucose.

GLUCOSE

• Other monosaccharides can easily be

converted to glucose or its metabolic
intermediates.

•Energy generation is a major function of

carbohydrate/glucose metabolism
 Major Pathways of CHO Metabolism
CHO Metabolism in Mammalian Cells can be classified into:
1. Glycolysis: Oxidation of glucose to pyruvate (aerobic
state) or lactate (anaerobic state)
2. Krebs cycle or Tricarboxylic Acid cycle: After oxidation
of pyruvate to acetyl CoA, acetyl CoA enters the Krebs
cycle for the aim of production of ATP.
3. Hexose monophosphate shunt (HMP) : Enables cells to
produce ribose-5-phosphate and NADPH.
4. Glycogenesis: Synthesis of glycogen from glucose, when
glucose levels are high.
Major Metabolic Pathways in CHO Metabolism
Cont’d

5. Glycogenolysis: Degradation of glycogen to

glucose when glucose is in short supply.
6. Gluconeogenesis: Formation of glucose from
noncarbohydrate sources.
7. Electron Transport Chain: The NADH and
succinate generated in the citric acid cycle are
oxidized, providing energy to power ATP
synthase in the mitochondrion.
Glycolysis: (Embden-Meyerhof
Glycolysis Pathway)
from the Greek glyk-, sweet, and lysis, splitting
• Glycolysis : Refers to the sequence of rxns by which glucose is
broken down to give pyruvate and energy.
• Occurs in the cell cytosol
• May be aerobic [Glucose  Pyruvate] summary of Rxn =
Glucose + 2ADP + 2Pi + 2NAD+ -- 2 pyruvate + 2ATP + 2NADH +
2H+ + 2H2O
OR

• Anaerobic [Glucose  Lactate] or Ethanol & acetic acid.

(Alcoholic Fermentation; alcohol + CO2))

• Summary of Rxn = Glucose + 2ADP + 2Pi ----- 2 Lactate + 2ATP +

2H2O
•
ANAEROBIC GLYCOLYSIS
• Occurs in cells that lack mitochondria
– eg RBCs.
• Under hypoxic conditions eg skeletal
muscle during strenuous exercise
• Glucose converted to lactate
• Energy is produced
AEROBIC PATHWAY
• Occurs in cells with mitochondria – eg
hepatocytes
• Under adequate oxygen supply
• Glucose is converted to pyruvate in the cytosol
• Pyruvate enters the mitochondria
• Pyruvate is converted to Acetyl-CoA
• Energy is yielded
 ALCOHOLIC FERMENTATION

• Occurs in microorganisms eg yeast, bacteria

• Glucose is converted to alcohol and CO2
• Reactions are basically anaerobic
• Energy is also produced
REACTIONS OF GLYCOLYSIS (10 STEPS)
 H
CH2O P C O
C O HCOH
6
CH2OH CH2OH CH2O P
5 O
H H H Dihydroxyacetone Glyceraldehyde
5
4 1 phosphate 3-phosphate
HO OH H
OH 2 NAD+ + 2 P
3 2 6
H OH Glucose (1 molecule) 2 NADH + 2H+

CH2O P
ATP
Glucokinase 1 HCOH
ADP C O P 1, 3-Bisphosphoglyceric acid
(2 molecules)
P OH2C O
2 ADP
O 7
H H
H 2 ATP
OH H CH2O P
HO OH
OH
H HCOH 3-Phosphoglyceric acid
OH Glucose 6-phosphate
COOH (2 molecules)
Phosphoglucoisomerase 2
Note: The irreversible 8
6
P OH2C O 1
CH2OH
Reactions (1, 3 and 10 ) CH2OH

5
HCO P 2-Phosphoglyceric acid
2
(2 molecules)
H H HO COOH
OH
4 3 9
OH H Fructose 6-phosphate
CH2
ATP
Phosphofructokinase 3 C O P Phosphoenolpyruvic acid
ADP (2 molecules)
COOH
P OH2C 2 ADP
O 10
CH2O P
2 ATP

H H HO
OH CH 3
OH H Fructose 1, 6-bisphosphate C O
Pyruvic acid
COOH (2 molecules)
4
Differences between Glucokinase & Hexokinase
Hexokinase Glucokinase
 Present in all tissues  Liver only
 Low Km for glucose (<0.1  Higher Km for glucose
mM)
 Strongly inhibited by G6P  Not inhibited by G6P

 Non-inducible enzyme, not  Inducible, synthesis induced by

affected by diabetes or insulin & repressed in diabetes
insulin

 Level of enzyme is not  Depends on glucose concentration

affected by fasting or high
CHO diet

 Has broad specificity Specific for glucose (phosphorylates

(phosphorylates all only glucose)
hexoses
 Glycolysis: Energy-Investment
In reactions 1-5 of glycolysis,
• Energy is required to add phosphate groups to
glucose.
• Glucose is converted to two three-carbon
molecules.

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GLYCOLYSIS: ENERGY INVESTMENT

5 5
2

Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 13

GLYCOLYSIS: ENERGY-PRODUCTION
In reactions 6-10 of glycolysis, energy is generated;
• Sugar phosphates are cleaved to triose
phosphates.
• Four ATP molecules are produced.

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Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings
 GLYCOLYSIS: REACTIONS 6-10

6
8 10

Copyright © 2007 by Pearson Education, Inc. Publishing as Benjamin Cummings 15

 GLYCOLYSIS: OVERALL REACTION
In glycolysis,
• Two ATP add phosphate to glucose and fructose-6-
phosphate.
• Four ATP are formed in energy-generation by direct
transfers of phosphate groups to four ADP.
• There is a net gain of 2 ATP and 2 NADH.

C6H12O6 + 2ADP + 2Pi + 2NAD+

Glucose

2C3H3O3- + 2ATP + 2NADH + 4H+

Pyruvate
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LEARNING CHECK
• In glycolysis, what compounds provide phosphate
groups for the production of ATP and at what
steps?
In reaction 7, phosphate groups from two
1,3-bisphosphoglycerate molecules are
transferred to ADP to form two ATP.

In reaction 10, phosphate groups from two

phosphoenolpyruvate molecules are used to
form two more ATP.
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ATP Generating Points In Glycolysis
LEARNING CHECK

What is “substrate–level phosphorylation” ?

substrate Level phosphorylation; Is the synthesis of ATP

coupled to the conversion of a substrate to a product
• ADP + Pi → ATP

• This is different from the synthesis of ATP in the Electron

Transport Chain (ETC) – by oxidative phosphorylation.

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 GLYCOLYSIS - SUMMARY

• In summary, a single glucose molecule in glycolysis

produces a total of 2 molecules of pyruvate, 2
molecules of ATP, 2 molecules of NADH

• 2 ATP molecules are used in steps 1 & 3, 2 ATP

molecules are generated in step 7 and 2 molecules
in step 10. This gives a total of 4 ATP molecules
produced
• If you subtract the 2 ATP molecules used in steps 1
& 3 from the 4 generated from steps 7&10, you end
up with a net total of 2 ATP molecules produced.
 REGULATION OF GLYCOLYSIS
• PFK-I is the major regulatory enzyme Rate of glycolysis is controlled primarily by
of glycolysis. In the liver only, PFK-1 allosteric regulation of the 3 key enzymes
is activated by fructose-2,6- (irreversible steps), hexokinase, PFK-1, and
bisphosphate (F-2,6-bisP). pyruvate kinase.
• PFK-II, the enzyme that synthesize Inhibitor Activator Enzyme
the activator F-2,6-bisP, is itself a
regulatory enzyme. It is inhibited by G-6-P AMP, ADP, Pi Hexokinase
citrate & ATP and by
phosphorylation. The reverse
reaction is catalyzed by fructose-2,6- NADH, H+, F-6-P, AMP, PFK-1
citrate, ATP F-2,6-bisP
bisphosphatase(F-2,6-bisPase).
(liver only)
• Hormones also regulate glycolysis
e.g., glucagon inhibits glycolysis by
repressing the synthesis of F-2,6-bisP. ATP, acetyl AMP, F-1,6- Pyruvate
CoA, bis P kinase
Insulin promotes glycolysis by phosphorylation
stimulating the synthesis of F-2,6-
January 4, 2024 21
bisP.
Learning Check
What are the Functions of Glycolysis?
 FUNCTIONS OF GLYCOLYSIS

1. Energy (ATP) provision

2. Provision of building blocks for biosynthesis
eg
- DHAP used in TAG synthesis in form of glycerol
-pyruvate for Alanine synthesis
-G6P used in many pathways (junction
molecule)
Learning Check
• DISCUSS BRIEFLY THE REGULATION OF GLYCOLYSIS
 Regulation of Glycolysis
Glycolysis is regulated by three enzymes,
• Reaction 1 Hexokinase is inhibited by high levels
of glucose-6-phosphate, which prevents the
phosphorylation of glucose.
• Reaction 3 Phosphofructokinase, an allosteric
enzyme, is inhibited by high levels of ATP and
activated by high levels of ADP and AMP.
• Reaction 10 Pyruvate kinase, another allosteric
enzyme is inhibited by high levels of ATP or acetyl
CoA. 25
Comments:
 The best known inhibitors of the glycolytic pathway
include:
2-Deoxyglucose: causes inhibition of hexokinase.
Sulfhydryl reagents (e.g. Hg-compounds and alkylating
agents as iodoacetate); inhibit glyceraldehydes-3-
phosphate dehydrogenase which has cysteine residue
in the active site.
Fluoride: A potent inhibitor of enolase. Thus, fluoride is
usually added to blood samples to inhibit glycolysis
before estimation of blood glucose.
•  Magnesium: Required for kinase reactions by forming
Mg-ATP complex. 26
THANK YOU

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