Biochemistry: Fates of Pyruvate

Fates of Pyruvate

• Pyruvate can be converted to Acetyl CoA in mitochondria by pyruvate dehydrogenase complex. This is required for the citric acid cycle.
• Pyruvate can be converted to lactate in the cytosol by lactate dehydrogenase (LDH) during anaerobic glycolysis.
• Pyruvate can be converted to oxalacetate in mitochondria by pyruvate carboxylase. This is required for gluconeogenesis.
• Pyruvate can be converted to alanine in the cytosol by alanine transaminase (ALT).

Formation of Acetyl CoA from Pyruvate

• Pyruvate is irreversibly converted to Acetyl CoA in the mitochondrial matrix by pyruvate dehydrogenase complex.
• This complex is composed of three enzymes and five coenzymes.
• The coenzymes are derived from water-soluble vitamins:
  • Thiamine pyrophosphate (TPP) from Thiamine (vitamin B1)
  • Lipoic acid
  • Coenzyme A from pantothenic acid (B5)
  • FAD from riboflavin (B2)
  • NAD+ from niacin (B3)
• Pyruvate dehydrogenase complex deficiency causes congenital lactic acidosis.

Citric Acid Cycle (Krebs Cycle, TCA)

• The citric acid cycle is the final pathway for carbohydrate, lipid, and protein catabolism.
• Acetyl CoA is the end product of carbohydrate, lipid, and protein oxidation.
• Acetyl CoA condenses with oxalacetate to form citrate, which is the first reaction of the cycle.
• The citric acid cycle produces:
  • 3 NADH
  • 1 FADH2
  • 1 ATP
• The NADH and FADH2 yield a total of 11 ATP (9 ATP from NADH and 2 ATP from FADH2) through oxidative phosphorylation.

Regulation of the Citric Acid Cycle

• The citric acid cycle is regulated by the cell's need for energy in the form of ATP.
• When ADP levels are high relative to ATP, the cycle speeds up, indicating a need for energy.
• When ATP levels are high, indicating adequate energy supply, the cycle is inhibited.
• The rat poison fluoroacetate inhibits the citric acid cycle by forming fluorocitrate which inhibits aconitase, leading to convulsions, cardiac arrhythmias and death.

This quiz explores the various fates of pyruvate, including its conversion to Acetyl CoA, lactate, oxalacetate, and alanine. It also discusses the importance of the pyruvate dehydrogenase complex and coenzymes derived from vitamins. Test your understanding of these metabolic pathways and their significance in cellular respiration.