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Y Biochemistry 2 > Citric Acid Cycle (Ben) > Flashcards

Citric Acid Cycle (Ben) Flashcards

1
Q

What is the first reaction of the citrate cycle?

Reactants?

Enzyme?

Product?

Notes?

A

Reactants: Oxaloacetate + Acetyl-CoA

Enzymes: Citrate Synthase

Products: Citrate + CoA-SH + H+

Notes: IRREVERSIBLE + oxaloacetate can be considered catalytic because it is regenerated by the cycle

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2
Q

What is the first part of the second reaction of the citrate cycle?

Reactants?

Enzyme?

Product(s)?

A

Dehydration of citrate to an intermediate…

Reactants: Citrate

Enzyme: Aconitase

Product: Cis-Aconitate Intermediate

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3
Q

What two things can inhibit aconitase and what results from this?

A
  • buildup of its product isocitrate
    • _​_results in free citrate which can be removed to the cytosol for fatty acid synthesis
  • fluoracetate - in plants or metabolized from chemo meds
    • ​inhibits aconitase via fluoracetyl-CoA > fluorocitrate formation + causes citrate accumulation
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4
Q

What is the 2nd part of the second reaction of the citrate cycle?

Reactants?

Enzyme?

Product(s)?

A

Rehydration of an intermediate to isocitrate…

Reactants: Cis-aconitate intermediate

Enzyme: Aconitase

Product: Isocitrate

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5
Q

What is the 1st part of the 3rd reaction of the citric acid cycle (acting on the isomer formed in reaction 2)?

Reactants?

Enzyme?

Product(s)?

Notes?

A

Dehydrogenation…

Reactant: Isocitrate + NAD+

Enzyme: Isocitrate Dehydrogenase

Product: Oxalosuccinate + NADH + H+

Notes: IRREVERSIBLE + product remains enzyme-bound for 2nd part of rxn

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6
Q

What is the 2nd part of the third reaction of the citrate cycle?

Reactants?

Enzyme?

Product(s)?

Notes/requirements?

A

Oxidative decarboxylation…

Reactants: Oxalosuccinate

Enzyme: Isocitrate Dehydrogenase

Product: α-Ketoglutarate

Notes: IRREVERSIBLE + requires Mg2+ or Mn2+

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7
Q

What is the fourth reaction of the citrate cycle, occurring after decarboxylation via isocitrate dehydrogenase?

Reactants?

Enzyme?

Product(s)?

Notes (especially about the enzyme)?

A

Another oxidative decarboxylation…

Reactants: α​-Ketoglutarate dehydrogenase + NAD+ + HS-CoA

Enzyme: α​-Ketoglutarate dehydrogenase complex

Product: Succinyl-CoA + NADH

Notes: IRREVERSIBLE + α​-KGDH Complex is very similar to PDH complex (same E3)

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8
Q

Considering that alpha-ketoglutarate dehydrogenase complex is so similar to PDH complex…

what are its prosthetic groups + cofactors?

A

Prosthetic Groups:

  • Thiamin Pyrophosphate
  • Lipoic Acid
  • FAD

Cofactors: NAD + CoA (via CoA-SH)

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9
Q

What is the 5th reaction of the citrate cycle, coming after the reaction catalyzed by an enzyme complex?

Reactants?

Enzyme?

Product(s)?

Notes?

A

Substrate level phosphorylation…

Reactants: Succinyl-CoA + Pi + GDP

Enzyme: Succinyl-CoA Synthetase

Products: Succinate + CoA-SH + GTP

Notes: GTP can pass the phosphoryl group to ADP via NDP Kinase

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10
Q

What is special about S_uccinyl-CoA Synthetase_ in different tissues with regard to its effect on nucleoside diphosphates?

A

Two isoenzymes exist:

Gluconeogenic tissues (liver/kidney): GDP/ADP-specific versions

  • GDP version makes GTP for decarboxylation of oxaloacetate to phosphoenolpyruvate
  • links citric acid cycle + gluconeogenesis

Non-gluconeogenic tissues: only ADP-specific version

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11
Q

What is the sixth reaction of the citrate cycle, following a substrate level phosphorylation?

Reactants?

Enzyme?

Product(s)?

A

Dehydrogenation of succinate…

Reactants: Succinate + FAD

Enzyme: Succinate Dehydrogenase

Products: Fumarate + FADH2

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12
Q

What is special about the location and function of succinate dehydrogenase?

A
  • it is a membrane-bound flavoprotein bound to the inner surface of the inner mitochondrial membranse
  • it is part of complex II of the respiratory chain
  • it reduces CoQ via electrons transported by its Iron-Sulfur Proteins
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13
Q

What is the 7th reaction of the citrate cycle, right after the step catalyzed by a membrane bound enzyme?

Reactants?

Enzyme?

Products?

Notes?

A

Hydration of fumarate…

Reactants: Fumarate

Enzyme: Fumarase

Product: L-Malate

Note: the hydration is stereospecific, always forming the L-enantiomer

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14
Q

What inhibits succinate dehydrogenase?

Via what kind of inhibition?

A

Malonate

  • via competitive inhibition
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15
Q

What is the 8th and final step of the citrate cycle, reforming the intial compound that contributes to the first step?

Reactants?

Enzymes?

Products?

A

Oxidization of malate…

Reactants: Malate + NAD+

Enzyme: Malate Dehydrogenase

Products: Oxaloacetate + NADH

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16
Q

What 3 citric acid cycle steps produce NADH?

A

​Remember: all dehydrogenase steps except succinate dehydrogenase.

  1. Isocitrate Dehydrogenase (oxidation of isocitrate to oxalosuccinate)
  2. Alpha-ketoglutarate Dehydrogenase (oxidative decarboxylation of AKG to succinyl-CoA)
  3. Malate Dehydrogenase (oxidation of L-malate to oxaloacetate)
17
Q

Which step of the citrate cycle produces FADH2?

A

Succinate Dehydrogenase

  • also technically E3 of AKGDH Complex I guess, but that remains bound to E3 as its prosthetic group
18
Q

Which step of the citrate cycle is a substrate-level phosphorylation?

A

Succinyl-CoA Synthetase

-

19
Q

What is special about the free energy change of the final step of the citrate cycle?

And because of this, what moves it forward?

A

non-spontaneous under standard conditions

  • driven by high [malate]/[oxaloacetate] and [NAD+]/[NADH] ratios
20
Q

Which two steps of the citrate cycle produce CO2?

A

​The two oxidative decarboxylations leading up to ADP/GDP phosphorylation

  1. Isocitrate Dehydrogenase (oxalosuccinate to AKG)
  2. AKG-Dehydrogenase Complex (AKG to Succinyl-CoA)
21
Q

What is the net reaction of the citrate cycle?

A
22
Q

What inhibits alpha-ketoglutarate dehydrogenase complex?

A

Arsenite

  • also high [ammonia]
23
Q

What are the 3 irreversible steps of the citrate cycle?

A
  1. Citrate Synthase
  2. Isocitrate Dehydrogenase
  3. AKG-Dehydrogenase Complex
24
Q

What activates the citrate cycle?

Think ratios of products and reactants.

A
  • low [NADH]/[NAD+]
  • low [ATP]/[ADP]
  • low [succinyl-CoA]/[CoA]
  • Ca2+ (as in working muscle)

Y Biochemistry 2 (24 decks)

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