Where does the TCA cycle occur and what is its purpose?
Location: Mitochondrial matrix Purpose: Oxidize acetyl-CoA to CO₂ and generate NADH, FADH₂, and GTP for ATP production
What are the overall products of 1 turn of the TCA cycle?
• 3 NADH • 1 FADH₂ • 1 GTP (≈ ATP) • 2 CO₂
Which steps of the TCA cycle produce NADH?
Which step of the TCA cycle produces FADH₂?
• Succinate → Fumarate
Which step of the TCA cycle produces GTP?
• Succinyl-CoA → Succinate
Which steps of the TCA cycle release CO₂?
• Isocitrate → α-ketoglutarate • α-ketoglutarate → Succinyl-CoA
Why is it called a “cycle”?
Because oxaloacetate is regenerated at the end to accept another acetyl-CoA
What is the action of fluoroacetate on the TCA cycle?
Fluoroacetate → fluorocitrate, which inhibits aconitase, slowing the TCA cycle
What causes Wernicke-Korsakoff syndrome (WKS)?
Thiamine (vitamin B1) deficiency, commonly due to chronic alcoholism
What are the symptoms of Wernicke-Korsakoff syndrome?
Wernicke (acute): • Confusion • Ataxia • Ophthalmoplegia Korsakoff (chronic): • Memory loss • Confabulation • Personality changes
What is the treatment for Wernicke-Korsakoff syndrome?
Immediate thiamine (B1) before glucose, plus nutrition and alcohol cessation
What are the 3 regulatory enzymes of the TCA cycle?
• Citrate synthase • Isocitrate dehydrogenase • α-Ketoglutarate dehydrogenase
How is citrate synthase regulated?
↓ inhibited by ATP, NADH ↑ activated by ADP
How is isocitrate dehydrogenase regulated?
↓ inhibited by ATP, NADH ↑ activated by AMP, Ca²⁺
How is α-ketoglutarate dehydrogenase regulated?
↓ inhibited by ATP, NADH ↑ activated by Ca²⁺
How are vitamins involved in the Krebs cycle? (B1, B2, B3, B5)
B1 (thiamine): TPP for α-ketoglutarate dehydrogenase B2 (riboflavin): FAD → FADH₂ B3 (niacin): NAD⁺ → NADH B5 (pantothenic acid): part of Coenzyme A