Bernstein L H, Grisham M B, Cole K D, Everse J
J Biol Chem. 1978 Dec 25;253(24):8697-701.
The mechanism that leads to an inhibition of enzyme activity in the presence of high concentrations of substrate was investigated with the two malate dehydrogenase isoenzymes obtained from pig heart. The inhibition is promoted by an abortive binary complex formed by the enzymes and the enol form of of oxalacelate. Neither the oxidized coenzyme nor the reduced coenzyme appears to be involved in the formation of this complex. These results suggest that the mechanism of substrate inhibition that occurs with the pig heart malate dehydrogenases is different from that observed with the lactate dehydrogenases from chicken hearts. The inhibition constants for oxalacetate are 2.0 mM with the mitochondrial enzyme and 4.5 mM with the cytoplasmic enzyme. Since the in vivo concentration of oxalacetate is reported to be about 10 micrometer, these data suggest that the substrate inhibition that is exhibited by the malate dehydrogenases may not be of any significance in vivo.
利用从猪心获得的两种苹果酸脱氢酶同工酶，对在高浓度底物存在下导致酶活性受到抑制的机制进行了研究。这种抑制作用是由酶与草酰乙酸烯醇式形成的无活性二元复合物所促进的。氧化型辅酶和还原型辅酶似乎均未参与该复合物的形成。这些结果表明，猪心苹果酸脱氢酶发生的底物抑制机制与鸡心乳酸脱氢酶所观察到的机制不同。草酰乙酸对线粒体酶的抑制常数为2.0 mM，对细胞质酶的抑制常数为4.5 mM。由于据报道草酰乙酸在体内的浓度约为10微摩尔，这些数据表明苹果酸脱氢酶所表现出的底物抑制在体内可能没有任何意义。
