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Biochemistry

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Carbohydrates

Question
20 out of 40
 

Which of the following inhibit the combination of acetyl co-A with oxaloacetate(AIIMS Nov 2010)



A Fumarate

B Malonate

C Fluroacetate

D Arsenite

Ans. C FluroacetateRef: Harper, 28th edition, Chapter 17, The Citric Acid Cycle……….

a. The initial reaction between acetyl-CoA and oxaloacetate to form citrate is catalyzed by citrate synthase, which forms a carbon-carbon bond between the methyl carbon of acetyl-CoA and the carbonyl carbon of oxaloacetate.

b. The thioester bond of the resultant citryl-CoA is hydrolyzed, releasing citrate and CoASH—an exothermic reaction.

c. Citrate is isomerized to isocitrate by the enzyme aconitase (aconitatehydratase); the reaction occurs in two steps: dehydration to cis-aconitate and rehydration to isocitrate.

d. Although citrate is a symmetric molecule, aconitase reacts with citrate asymmetrically, so that the two carbon atoms that are lost in subsequent reactions of the cycle are not those that were added from acetyl-CoA.

e. This asymmetric behavior is the result of channeling—transfer of the product of citrate synthase directly onto the active site of aconitase, without entering free solution.

f. This provides integration of citric acid cycle activity and the provision of citrate in the cytosol as a source of acetyl-CoA for fatty acid synthesis.

g. The poison fluoroacetate is toxic, because fluoro acetyl-CoA condenses with oxaloacetate to form fluoro citrate, which inhibits aconitase, causing citrate to accumulate.

Four Key Enzymes in the Citric Acid Cycle

1. Pyruvate Dehydrogenase Complex (PDH) "step O".

  1. Oxidative decarboxylation produces CO2 and NADH.
  2. The acetyl-CoA product is a ("high-energy") thioester.
  3. Regulation
    1. ATP and NADH are inhibitors.
    2. Phosphorylation of PDH inhibits the reaction.
    3. Ca2+ activates the dephosphorylation.

2. Citrate Synthase: step 1.

  1. Irreversible condensation reaction.
  2. Allosteric inhibitors: ATP and NADH.
  3. Recall that citrate (in the cytosol) is an inhibitor of PFK in glycolysis.

This enzyme is inhibited by fluoroacetate

3. Isocitrate Dehydrogenase: step 3.

  1. Oxidative decarboxylation produces CO2 and NADH.
  2. The a-ketoglutarate product is a 5-carbon dicarboxylic acid.
  3. Regulation
    Allosteric inhibitors: ATP and NADH.
    Allosteric activators: ADP and NAD+.

4. a-Ketoglutarate Dehydrogenase Complex: step 4.

  1. Oxidative decarboxylation produces CO2 and NADH.
  2. The succinyl-CoA product is a thioester.
  3. The complex is similar to the PDH complex.

Carbohydrates Flashcard List

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