Krebs Cycle

• Pyruvate dehydrogenase requires:
  • Vitamin B1: Thiamine/TPP, transaldolase.
  • Vitamin B5: Pantothenic acid, CoA
  • Vitamin B2: Riboflavin, FADH2
  • Vitamin B3: Niacin, NAD⁺
• Pyruvate carboxylase supplies the oxaloacetate needed.
• TCA is inhibited by ATP, NADH, Acetyl CoA (inhibits PDH), citrate (inhibits citrate synthase), succinyl CoA (aKG DH)
• TCA is stimulated by Ca²⁺ (electrical stimulation of muscle)
• General reaction scheme:
  1. Transport of pyruvate into mitochondria (Oxidative decarboxylation): Pyruvate → Acetyl CoA.
     • Catalyzed by pyruvate dehydrogenase (PD)
       • Cofactors derived from B₁ through B₅ and lipoic acid.
     • Arsenic inhibits lipoic acid. Symptoms: vomiting, rice water stools, garlic breath
  2. Preparing for decarboxylations by making β-keto carboxylate: Oxaloacetate + Acetyl CoA → Citrate → Isocitrate → [Oxalosuccinate].
     • [Oxalosuccinate] is β-keto carboxylate, so it's unstable because it's dying to decarboxylate.
  3. Decarboxylations: [Oxalosuccinate] → α-Keto glutarate → Succinyl-CoA.
  4. Remake Oxaloacetate to complete cycle: Succinyl-CoA → Succinate → Fumarate → Malate → Oxaloacetate.
• All the dehydrogenases use their redox reactions to make NADH (for succinate DH it's FADH₂)
• Succinyl-CoA synthase is backwards, because it's actually used for succinyl-CoA → succinate.
  • Succinyl-CoA synthase takes GDP and makes GTP.
  • However, it was fed GTP in an experiment, which drove the reaction backwards, hence the name succinyl-CoA synthase.
• Occurs in the mitochondrial matrix.
• TCA Intermediates: acetyl CoA (fatty acid), oxaloacetate (gluconeogenesis, asp), pyruvate (ala), aKG (glu), succinate (val, ile)
• Excess carbohydrate, protein, can be converted to carbohydrate, protein (except essential amino acids), and fat.

Chemical structures