|
|
|
The isocitrate dehydrogenase reaction is irreversible and is carefully
regulated to prevent any decrease in isocitrate or increase in ?-ketoglutarate.
The reaction is moved by substrate availability (isocitrate, NAD+, Mg2+/Ca2+),
product inhibition (excess NADH and ?-ketoglutarate), and competitive feedback
inhibition (increases in ATP) (6). Isocitrate dehydrogenase is used to
catalyze the oxidative decarboxylation of isocitrate(1).
Isocitrate + NAD+ -> a-ketoglutarate + CO2 + NADH (1) The transformation of isocitrate to ?-ketoglutarate by isocitrate dehydrogenase involves the conversion of NAD+ to NADH and yields one molecule of CO2 (3). There is a large negative free energy change in the citric acid cycle step involving isocitrate dehydrogenase (6). The overall free energy for the reaction in either isoform is -8.4kJ/mol. isocitrate dehydrogenase lowers the Km of isocitrate without lowering the Vmax (6). The decarboxylation of (2R, 3S) - Isocitrate, a secondary alcohol, is a reaction of ?-keto acid, like in the acetoacetic ester synthesis (4).During the TCA cycle, oxalosuccinate remains bound to isocitrate dehydrogenase (2). The phosphorylation of isocitrate dehydrogenase is a branchpoint between the glyoxylate bypass and the Krebs cycle. The bypass is needed to accumulate carbon for biosynthetic processes (11). Isocitrate dehydrogenase is synthesized at a slower rate during glycolytic adaptations, this may be due to a long-lived messenger RNA that produces an unwanted protein or may be caused by a decrease in the rate of enzyme initiation (14). |
Fig. 4 A pictorial sequence of the reaction and mechanism of isocitrate dehydrogenase in the Krebs cycle (17).
Fig. 5 When acetate is the sole carbon source, isocitrate is diverted to the glyoxylate bypass by isocitrate dehydrogenase (10). |
      |
