THE FATE OF PYRUVATE

BIC 203 (Lecture 2)

C. Z. Uche
 THE FATE OF PYRUVATE
• The fate of pyruvate from glycolysis depends
on:
 The organism involved
 The tissue in question (type of cell)
 The redox state of the tissue (O2 availability)
THE FATE OF PYRUVATE
(JUNCTION MOLECULE)
ANAEROBIC GLYCOLYSIS
Alcoholic Fermentation
• Occurs in anaerobic microorganisms such as yeast.
• Decarboxylates pyruvate to acetaldehyde, which is
reduced to ethanol.
• Regenerates NAD+ to continue glycolysis.
• NADH is reused to regenerate NAD+
ALCOHOLIC FERMENTATION

pyruvate decarboxylase

Alcohol DH2ase
ANAEROBIC GLYCOLYSIS
Lactic Acid Fermentation
 ANAEROBIC GLYCOLYSIS CONTD
• Occurs in cells without mitochondria eg RBCs
• Also during inadequate O2 supply eg skeletal
muscle during strenuous exercise.
• Pyruvate is converted/reduced to lactate.
• NADH produced in G3P-DH2ase (rxn 6 in glycolysis)
is used as reducing agent.
• The NAD+ produced ensures continuity of glycolysis
• Rxn is catalyzed by lactate DH2ase and is
reversible.
•
PYRUVATE: ANAEROBIC CONDITIONS
Under anaerobic conditions (without oxygen),
• Pyruvate is reduced to lactate.
• NADH oxidizes to NAD+ allowing glycolysis to continue.

O O lactate

|| || dehydrogenase
CH3—C—C—O- + NADH + H+
pyruvate
OH O
| ||
CH3—CH—C—O- + NAD+
lactate

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 LACTATE IN MUSCLES
During strenuous exercise,
• Oxygen in the muscles is depleted.
• Anaerobic conditions are produced.
• Lactate accumulates. OH
│
C6H12O6 + 2ADP + 2Pi 2CH3–CH–COO- + 2ATP
glucose lactate
• Muscles tire and become painful.
After exercise, a person breathes heavily to repay
the oxygen debt and reform pyruvate in the liver.
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LEARNING CHECK
• Discuss briefly lactic acidosis
LACTIC ACIDOSIS
• Arises in the skeletal muscle during strenuous exercise
• Under this condition, NADH production from glycolysis
and TCA cycle rxns far exceeds the oxidative capacity of
the ETChain
• NADH/NAD+ ratio is high and favours lactate formation
from pyruvate
• Lactate accumulates in the muscle causing a drop in
intracellular pH
• Causes cramps/stiffness in the muscle (lactic acidosis)
• There is increased blood lactate, and decreased
bicarbonate and low pH
The Cori cycle: processing lactate
made during anaerobic exercise

Gerti and Carl Cori won 1947 Nobel

Prize in physiology / medicine for
discovery of the enzyme that starts
the conversion of glycogen to
glucose.
 CORI CYCLE
• Serves to prevent Lactic acidosis.

• Lactate is produced (high conc) in the muscle

during strenuous exercise from glucose.
• Lactate moves to liver via blood.
• Is converted to glucose by gluconeogenesis in the
liver.
• Glucose moves through blood back to muscle to
complete the cycle
The Fate of Pyruvate
 AEROBIC GLYCOLYSIS CONTD
• Pyruvate formed in the cytosol is transported into
the mitochondrion
• Here it is converted to acetyl-CoA by the enzyme
pyruvate DH2ase
• Five (5) coenzymes participate in the rxn – CoA,
NAD, FAD, Lipoic acid and TPP, with Mg2+ as cofactor
• Acetyl-CoA may be used in the TCA cycle or in
lipogenesis
• Rxn is irreversible – reason glucose is not
synthesized from fat (Acetyl-CoA)
 PYRUVATE DEHYDROGENASE COMPLEX
• Pyruvate DH2ase is a complex enzyme

• Has 3 components – E1, E2, E3

– Pyruvate dehydrogenase – Decarboxylation of pyruvate
using TPP
– Dihydrolipoyl transacetylase – Transfer of 2-C fragment
to CoA using lipoic acid
– Dihydrolipoyl dehydrogenase – Reoxidation of lipoic
acid using the NAD-FAD system
Mechanism of action of Pyruvate DH2ase complex
SUMMARY

Under aerobic conditions (oxygen present),

• Three-carbon pyruvate is decarboxylated.
• Two-carbon acetyl CoA and CO2 are produced.

O O pyruvate || ||
dehydrogenase
CH3—C—C—O- + HS—CoA + NAD+
pyruvate
O
||
CH3—C—S—CoA + CO2 + NADH
acetyl CoA
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Learning Check

• Discuss the 3 possible fates of Pyruvate

PATHWAYS FOR PYRUVATE

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

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