Podcast
Questions and Answers
Which molecules promote PDH kinase activity?
Which molecules promote PDH kinase activity?
- FADH2, malate, oxaloacetate
- NAD+, CoA, pyruvate
- ATP, NADH, acetyl CoA (correct)
- GTP, NADPH, succinyl CoA
What inhibits PDH kinase activity?
What inhibits PDH kinase activity?
- FADH2, malate, oxaloacetate
- GTP, NADPH, succinyl CoA
- ATP, NADH, acetyl CoA
- NAD+, CoA, pyruvate (correct)
Which deficiency results in an inability to convert pyruvate to acetyl CoA?
Which deficiency results in an inability to convert pyruvate to acetyl CoA?
- Lactate dehydrogenase deficiency
- Glycolysis deficiency
- Pyruvate dehydrogenase complex deficiency (correct)
- Krebs cycle deficiency
What is the major source of ATP in the cell?
What is the major source of ATP in the cell?
Which of the following is a symptom of PDH complex deficiency?
Which of the following is a symptom of PDH complex deficiency?
Which molecules are involved in the covalent regulation of the PDH complex?
Which molecules are involved in the covalent regulation of the PDH complex?
What is the effect of thiamine pyruvate dehydrogenase (PDH) deficiency?
What is the effect of thiamine pyruvate dehydrogenase (PDH) deficiency?
How does arsenic poisoning affect pyruvate dehydrogenase complex (PDH) and glycolysis?
How does arsenic poisoning affect pyruvate dehydrogenase complex (PDH) and glycolysis?
Which vitamin deficiency is associated with rapid conversion of pyruvate to lactate in thiamine-deficient alcoholics?
Which vitamin deficiency is associated with rapid conversion of pyruvate to lactate in thiamine-deficient alcoholics?
What is the end product inhibition example seen in the regulation of pyruvate dehydrogenase (PDH)?
What is the end product inhibition example seen in the regulation of pyruvate dehydrogenase (PDH)?
How is pyruvate dehydrogenase complex (PDH) regulated through phosphorylation and dephosphorylation?
How is pyruvate dehydrogenase complex (PDH) regulated through phosphorylation and dephosphorylation?
Which coenzyme derived from water-soluble vitamins is involved in the pyruvate dehydrogenase complex?
Which coenzyme derived from water-soluble vitamins is involved in the pyruvate dehydrogenase complex?
Which enzyme catalyzes the synthesis of citrate from acetyl CoA and oxaloacetate?
Which enzyme catalyzes the synthesis of citrate from acetyl CoA and oxaloacetate?
What inhibits citrate synthase, the enzyme responsible for citrate synthesis?
What inhibits citrate synthase, the enzyme responsible for citrate synthesis?
Which enzyme is inhibited by fluoro-acetate in the conversion of citrate to cis-aconitate?
Which enzyme is inhibited by fluoro-acetate in the conversion of citrate to cis-aconitate?
What is the product of the oxidative decarboxylation of α-ketoglutarate to succinyl CoA?
What is the product of the oxidative decarboxylation of α-ketoglutarate to succinyl CoA?
What inhibits the complex that catalyzes the oxidative decarboxylation of α-ketoglutarate?
What inhibits the complex that catalyzes the oxidative decarboxylation of α-ketoglutarate?
Which modulator activates the oxidative decarboxylation of isocitrate to α-ketoglutarate?
Which modulator activates the oxidative decarboxylation of isocitrate to α-ketoglutarate?
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Study Notes
Allosteric Regulation of PDH
- Calcium released during muscle contraction stimulates PDH
- PDH kinase is promoted by ATP, NADH, and acetyl CoA, while it is inhibited by NAD+, CoA, and pyruvate
Pyruvate Dehydrogenase Complex Deficiency
- Deficiency in the α subunit of the dimeric E1 component of the PDH complex is the most common biochemical cause of congenital lactic acidosis
- Symptoms include neurodegeneration, muscle spasticity, and early death in the neonatal onset form
- There is no proven treatment, but dietary restriction of carbohydrates and supplementation with thiamine may reduce symptoms in select patients
Tricarboxylic Acid Cycle (Krebs Cycle)
- Final common pathway for the oxidation of carbohydrates, amino acids, and fatty acids
- Occurs exclusively in the mitochondria and is the major source of ATP
- Aerobic process that requires oxygen and is mainly catabolic with some anabolic features
Pyruvate Dehydrogenase Complex
- Composed of three enzymes and five coenzymes derived from water-soluble vitamins
- Coenzymes include thiamine pyrophosphate (derived from vitamin B1), NAD+, FAD (derived from riboflavin), lipoic acid, and coenzyme A (derived from pantothenic acid)
- Deficiency in thiamine (vitamin B1) inhibits PDH activity and causes accumulation of pyruvate, leading to lactic acidosis
Regulation of Oxidative Decarboxylation of Pyruvate
- PDH is a good example of end-product inhibition by acetyl CoA and NADH
- PDH is also regulated by phosphorylation and dephosphorylation (covalent regulation)
- PDH is active as a dephosphoenzyme and inactive as a phosphoenzyme
Tricarboxylic Acid Cycle Reactions
- Citrate synthase catalyzes the synthesis of citrate from acetyl CoA and oxaloacetate
- Citrate inhibits phosphofructokinase-1 (PFK-1) and activates acetyl CoA carboxylase
- Aconitase catalyzes the isomerization of citrate to isocitrate
- Isocitrate undergoes oxidative decarboxylation to α-ketoglutarate, which is inhibited by fluoro-acetate
Inhibition of Pyruvate Dehydrogenase
- Arsenic poisoning inhibits pyruvate dehydrogenase and α-ketoglutarate dehydrogenase by binding to the sulfhydryl groups of dihydrolipoic acid
- Citrate also inhibits phosphofructokinase-1 (PFK-1) and activates acetyl CoA carboxylase
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