Citric acid cycle Flashcards

1
Q

Location, function, condition

A
  • mitochondrial matrix
  • reoxidize electron carriers to generate ATP
  • aerobic
  • amphibolic:oxidation, carbon skeletons for gluconeogenesis, acetyl CoA for FA synthesis, interconversion of AAs
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2
Q

Acetyl-CoA -> Citrate

A

Acety-CoA/Oxaloacetate -> Citrate + SH-CoA

  • IRREVERSIBLE
  • enzyme: CITRATE SYNTHASE
  • condensation
  • overall deltaG=-31,5kJ/mol
  • first committed step
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3
Q

Allosteric regulation of citrate synthase

A
inhibited by:
high ATP
high NADH
high succinyl-CoA
high citrate conc.
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4
Q

Citrate -> Isocitrate

A

Citrate->cis-Aconitate->Isocitrate

  • dehydration- hydration
  • reversible
  • enzyme: ACONITASE (Fe-S protein, inhibited by fluoroacetate, serves as enzyme-bound intermediate)
  • channeling
  • citrate prochiral
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5
Q

Isocitrate -> alpha-ketoglutarate

A

Isocitrate + NAD+ -> alpha-ketoglutarate + NADH + CO2

  • IRREVERSIBLE
  • oxidative decarboxylation (requires Mg2+ or Mn2+)
  • enzyme: ISOCITRATE DEHYDROGENASE (3 isoenzymes)
  • rate limiting step
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6
Q

Allosteric regulation of Isocitrate DH

A
-inhibited by:
high ATP
high NADH
-activated by:
high ADP
high NAD+
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7
Q

Alpha-ketoglutarate -> Succinyl CoA

A

Alpha-ketoglutarate + NAD+ + SH-CoA -> Succinyl CoA + NADH + CO2

  • IRREVERSIBLE
  • oxidative decarboxylation
  • enzyme: ALPHA-KETOGLUTARATE DEHYDROGENSE
    (cofactors: TPP, lipoic acid, FAD, NAD+, CoA)
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8
Q

Allosteric regulation of alpha-ketoglutarate DH

A
inhibited by:
high ATP
high NADH
high succinyl-CoA
(also inhibited by arsenate and NH3)
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9
Q

Succinyl CoA -> Succinate

A

Succinyl CoA + GDP + Pi -> Succinate + SH-CoA + GTP

  • reversible
  • substrate-level phosphorylation
  • enzyme: SUCCINATE THIOKINASE/ SUCCINATE CoA SYNTHASE

GTP used by PEP carboxykinase (OAA –> PEP)

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10
Q

Succinate -> Fumarate

A

Succinate + FAD -> Fumarate + FADH2

  • reversible
  • dehydrogenation
  • enzyme: SUCCINATE DEHYDROGENASE (present in inner membrane, FAD as coenzyme, malonate competitively inhibits)
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11
Q

Fumarate -> Malate

A

Fumarate + H2O -> (L) Malate

  • reversible
  • hydration
  • enzyme: FUMARASE
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12
Q

Malate -> Oxaloacetate

A

Malate + NAD+ -> Oxaloacetate + NADH

  • reversible
  • dehydrogenation
  • enzyme: MALATE DEHYDROGENASE (not spontaneous in normal condition, pushed forward by high malate/OAA ratio and NAD+/NADH ratio)
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13
Q

Intermediates of cycle

A
  • not produced/consumed
  • becomes catalytic cofactors
  • consumed in other processes -> resynthesized (anaplerosis)
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14
Q

Vitamins in TCA

A

Riboflavin (FAD, cofactor in succinate DH)
Niacin (NAD+, electron acceptor for isocitrate DH, alpha-ketoglutarate dh, malate dh)
Thiamin (thiamin diphosphate, coenzyme for decarboxylation in alpha-ketogluterate dh rxn)
Pantothenic acid (coenzyme A)

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