BIOCHEMISTRY - L. Stryer - 1984

VOLUME 2

PART II GENERATION AND STORAGE OF METABOLIC ENERGY

CHAPTER 13. THE CITRIC ACID CYCLE

13.3. Oxaloacetate Condenses with Acetyl-Coenzyme A to Form Citrate

The cycle begins with the Condensation of a four-carbon component, oxaloacetate, and a two-carbon component, the acetyl group of acetyl-CoA. Oxaloacetate reacts with acetyl-CoA and H₂O to yield citrate and CoA.

This reaction, an aldol condensation followed by Hydrolysis, is catalyzed by citrate synthase (originally called the condensing enzyme). Oxaloacetate first condenses with acetyl-CoA to form citryl-CoA, which is then hydrolyzed to citrate and CoA. The hydrolysis of citryl-CoA drives the overall reaction strongly in the direction of citrate synthesis.

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13.4. Citrate Is Isomerized to Isocitrate

To enable The oxidative decarboxylation of the six-carbon compound, citrate must be isomerized to isocitrate. This isomerization is accomplished by a dehydration followed by a Hydration step, resulting in the interchange of H and OH. The enzyme catalyzing both reactions is called aconitase, because the presumed intermediate is cis-aconitate.

13.5. Isocitrate Is Oxidized and Decarboxylated to alpha-Ketoglutarate

We now arrive at the first of the four oxidation-reduction reactions of The Citric Acid Cycle. The Oxidative Decarboxylation of isocitrate is catalyzed by isocitrate dehydrogenase:

Isocitrate + NAD ⇄ α-Ketoglutarate + СO₂ +NADH.

The intermediate in this reaction is oxalosuccinate, which rapidly loses СO₂ while still bound to the enzyme to form α-ketoglutarate.

The rate of α-ketoglutarate formation plays a crucial role in regulating the overall rate of the cycle, as we will discuss later (Sec. 13.18). It should also be noted that There are two types of isocitrate dehydrogenases: one is NAD⁺-dependent, and the other is nicotinamide adenine dinucleotide phosphate (NADP⁺)-dependent. The NAD⁺-dependent enzyme, located in the Cell/35.html">Mitochondria, is essential for The Citric Acid cycle, whereas the NADP⁺-dependent enzyme, present in both mitochondria and Cytoplasm, serves a different metabolic function.