TCA

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Author:
Anonymous
ID:
103913
Filename:
TCA
Updated:
2011-09-23 22:32:32
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TCA Pyruvate Dehydrogenase
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Description:
Med School - TCA and Pyruvate Dehydrogenase
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  1. What cofactors are used by the pyruvate dehydrogenase complex and what are their origins?
    • TPP: Thiamine
    • Lipoate
    • FAD: Riboflavin
    • NAD+: Niacin
    • Coenzyme A: Pantahenate
  2. What are the 3 enzymes found in the PDC?
    • Pyruvate Decarboxylase
    • Dihydrolipoyl Transacetylase
    • Dihydrolipoyl Dehydrogenase
  3. What 2 regulatory enzymes are used to regulate PDC?
    • PDC-Kinase
    • PDC-Phosphatase
  4. How does PDC-Kinase regulate the PDC? What are its activators/inactivators?
    • It phosphorylates PDC and thereby inactivates it
    • (+) NADH and Acetyl-CoA
    • (-) ADP and Pyruvate
  5. How does PDC-Phosphatase regulate the PDC? What is it regulated by?
    • It removes the P group
    • Regulated by Calcium
  6. What happens to the PDC when energy level is high or when the O2 level is low?
    It is turned off!
  7. Describe the severe form of PDC deficiency?
    • Severe lactic acidosis at birth
    • Death in neonatal period
  8. Describe the less severe form of PDC deficiency?
    • Lactic acidosis moderate at birth
    • Psychomotor retardation with increasing age
  9. Where do the majority of PDC-deficiencies occur?
    Alpha subunit of E1
  10. During what reactions is NADH formed in the TCA?
    • Isocitrate --> Alpha-KG (isocitrate DH)
    • Alpha-KG --> Succinyl-CoA (Alpha-KG DH)
    • Malate --> Oxaloacetate (Malate DH)
  11. When is FADH2 formed in the TCA?
    Succinate --> Fumirate (succinate DH)
  12. When is GTP formed in the TCA?
    Succinyl-CoA --> Succinate (Succinyl-CoA Synth)
  13. What intermediates from the TCA make AA?
    Oxaloacetate and Alpha-KG
  14. What intermediates from the TCA make FA and sterols?
    Citrate
  15. What intermediates from the TCA go to gluconeogenesis?
    Malate
  16. What intermediates from the TCA make heme groups?
    Succinyl-CoA
  17. What is the main anaplerotic reaction for the TCA cycle?
    Pyruvate --> Oxaloacetate (pyruvate carboxylase)
  18. How is pyruvate carboxylase regulated and what is its main cofactor?
    • Main cofactor: Biotin
    • Regulation: (+) Acetyl-CoA
  19. What happens during a pyruvate decarboxylase deficiency?
    • Mild-moderate lactic acidemia early in life
    • Mental retardation due to glutamine synthesis in brain
  20. What 3 steps are regulated within the TCA?
    • Oxaloacetate --> Citrate (citrate synthase)
    • Isocitrate --> Alpha-KG (isocitrate DH)
    • Alpha-KG --> Succinyl-CoA (Alpha-KG DH)
  21. How is citrate synthase regulated in the TCA?
    • Oxaloacetate availability
    • (-) Citrate, NADH, ATP
    • (+) NAD+, ADP
  22. How is Isocitrate DH regulated in the TCA?
    • (-) NADH
    • (+) ADP, Ca ++
  23. How is Alpha-KG regulated in the TCA?
    • (-) Succinyl-CoA, NADH, ATP
    • (+) ADP, Ca++
  24. What symptoms are seen in a fumirase deficiency and what is elevated?
    • Symptoms: Neurological and encephalomyopathy
    • Elevated: Fumaric acid, succinate, Alpha-KG, citrate and malate (urine)
  25. What symptoms are seen in an Alpha-KG deficiency?
    • Infantile: Lactic Acidosis
    • Childhood: Psychomotor retardation
    • Sudden death, myocardiopathy, hepatic disorders
  26. What symptoms are seen in a Thiamine deficiency and what is it caused by?
    • Cause: Chronic alcoholism, dietary
    • Symptoms: Inhibition of alpha-KG and PDC

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