Concerted Inhibition of Isocitrate Dehydrogenase by Glyoxylate Plus Oxalacetate*

Nicotinamide Adenine Dinucleotide Phosphate-specific Isocitrate Dehydrogenase from a Higher Plant

“…Concerted inhibition of the NADP+-specific isocitrate dehydrogenase by glyoxylate and oxalacetate has been reported for the enzyme from a number of sources (15,(17)(18)(19) and has been related to the operation of the tricarboxylic acid and glyoxylic acid cycles. This inhibition, however, has also been found in the enzyme from pig heart (19), even though mammalian systems do not possess the glyoxylate cycle.…”

“…Nicotiniamide adenine dintucleotide plhosphate-specific isocitrate dehydrogenase was extracted from etiolated pea (Pisurn satirum L.) seedlings and was purified 65- (15,(17)(18)(19). The importance of these findings when considering metabolic regulation is difficult to assess since the function of the enzyme in the cell of eucaryotic organisms which also possess the NAD+-specific enzyme is not known.…”

“…It has been sug-gested that the principal regulation of the enzyme is by the ratio of NADH to NAD+ (5,9,10 (23). The enzyme from bacterial (14,18,19), protozoan (15)(16)(17) and pig heart sources (2, 3) has recently been studied and in all cases has shown to have normal kinetics with respect to the substrates. In contrast to the NAD+-specific enzyme it readily catalyzes the reactions both in the forward direction (NADP+ reduction) and in the reverse direction.…”

“…It has been suggested that the NADP+-specific enzyme is regulated by the concentration of ATP in the cell (14,16). There are also indications that there is a concerted inhibition when glyoxylate and oxalacetate are added together (15,(17)(18)(19). The importance of these findings when considering metabolic regulation is difficult to assess since the function of the enzyme in the cell of eucaryotic organisms which also possess the NAD+-specific enzyme is not known.…”

Purification and Characterization of NADP+-Linked Isocitrate Dehydrogenase fromPaecilomyces varioti

“…3) with the Ki value of 0.42 mM. This pattern of inhibition by oxalacetate was different from that reported to be "mixed" shown in the enzymes from Brevibacterium flavum 20 ) and Thermus fla- VUS,21) or to be "competitive" in Crithidia fasciculata.…”