L.10 TCA Cycle Diseases

Question 1

Thiamine (B1) Deficiency

Answer 1

• Decreased Pyruvate Dehydrogenase activity
• Affects tissues with high ATP production rate (skeletal/heart muscle, CNS)
• Beriberi (weight loss, limb weakness, arrhythmia, edema)
• Wernicke-Korsakoff Syndrome (impaired brain function)
• Alcohol decreases thiamine absorption

Question 2

Congenital Lactic Acidosis

Answer 2

• Pyruvate Dehydrogenase deficiency
• Pyruvate not converted to Acetyl CoA
• Pyruvate converted to lactic acid –> lactic acidosis
• Neurological problems (deficiency of carbons entering TCA cycle, brain is sensitive to acidosis)
• Tx: low carb/high fat diet

Question 3

Arsenate Poisoning

Answer 3

• Arsenate inhibits enzymes that use lipoic acid as cofactor
• Glyceraldehyde 3P Dehydrogenase (Glycolysis step)
• Pyruvate Dehydrogenase (Links glycolysis/TCA)
• a-Ketoglutarate Dehydrogenase (TCA step)
• Causes pyruvate/lactate accumulation
• Causes neurological problems/death