Notes on Pyruvate Metabolism

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What is Pyruvate?

• Pyruvate is an important product of glycolysis.

• Pyruvate undergoes three types of metabolisms: Anaerobic homolactic fermentation, aerobic oxidation (aka glycolysis), and anaerobic alcoholic fermentation.

Notes on Anaerobic (Homolactic) Fermentation

• For glycolysis to continue, NAD+ has to be recycled.

• Under anaerobic conditions, NAD+ is replenished by reduction of pyruvate in an extension of the glycolytic pathway.

• In muscle, during intense activity, oxygen has been depleted, but the demand of ATP still remains high.

• Under these conditions, lactate dehydrogenase catalyzes the oxidation of NADH of pyruvate to yield NAD+ and lactate.

• This is the reaction 11 of glycolysis.

• The overall process of anaerobic glycolysis in muscle can be represented as: Glucose + 2 ADP + 2 Pi = 2 lactate + 2 ATP + 2 H2O + 2 H+.

• Much of the lactate, the end product of anaerobic glycolysis, is exported from the muscle via the blood to the liver where it is reconverted to glucose.

• Muscle soreness is not caused by lactic acid buildup per se, but due to accumulation of glycolytically generated acid.

• A saying among hunters is that the meat of animals that have died of exhaustion from running is sour due to lactic acid buildup.

• Reaction of Anaerobic (Homolactic) Fermentation: The pro-R hydride is transferred from C4 of NADH's nicotinamide ring to C2 of pyruvate with the concomitant transfer of a proton from the imidazolium moiety of His 195 to pyruvate O2, thereby yielding NAD+ and lactate.

Notes on Anaerobic (Alcoholic) Fermentation

• Under anaerobic conditions in yeast, NAD+ is regenerated in a manner that has been of importance to mankind for thousands of years: the conversion of pyruvate to ethanol and CO2.

• Yeast employs ethanol as a kind of antibiotic to eliminate competing organisms.

• There are two main reactions of alcoholic fermentation: the decarboxylation of pyruvate to form acetaldehyde and CO2 as catalyzed by pyruvate decarboxylase, and the reduction of acetaldehyde by NADH to form ethanol in a reaction catalyzed by alcohol dehydrogenase (ADH).

• Note: pyruvate decarboxylase is not present in animals. It also contains a co-enzyme thiamin pyrophosphate (TPP), also called thiamin diphosphate (ThDp).

• TPP has a reactive thiazolium ring.

• TPP is also involved in decarboxylation reactions.

• Thiamine (vitamin B1) which is neither stored nor synthesized in significant amounts by tissues of most vertebrates is required in their diets. Its deficiency results in a fatal disease called Beriberi.

• Thiamine is present in the outer layers of rice (also known as brown rice).

Thus, both homolactic and alcoholic fermentation have the same function: the anaerobic regeneration of NAD+ for continuing glycolysis.

Energetics of Fermentation:

• Glucose = lactate + 2H+ -196 kJ/mol

• Glucose = 2CO2 + 2 ethanol -235 kJ/mol

Additional Readings:

Basic Biochemistry

1. Nucleic Acid Structure and Organization
2. DNA Replication and Repair
3. Transcription and RNA Processing
4. Genetic Code, Mutations, and Translation
5. Genetic Regulation
6. Recombinant DNA
7. Amino Acids, Proteins, Enzymes
8. Hormones
9. Vitamins
10. Energy Metabolism
11. Glycolysis and Pyruvate Dehydrogenase
12. Citric Acid Cycle and Oxidative Phosphorylation
13. Glycogen, Gluconeogenesis, and Hexose Monophosphate Shunt
14. Lipid Synthesis and Storage
15. Lipid Mobilization and Catabolism
16. Amino Acid Metabolism Disorders
17. Purine and Pyrimidine Metabolism
18. Electron Transport
19. Citric Acid Cycle and Glyoxylate Cycle
20. Glycolysis
21. Pyruvate Metabolism
22. Mitochondrial ATP formation
23. Gluconeogenesis
24. Glycogen Metabolism
25. Nitrogen Fixation (Metabolism) reactions, and Heme Metabolism
26. Amino Acid Metabolism
27. What is Medium Chain Acyl-CoA Dehydrogenase Deficiency (MCADD)?

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