Biellmann J F, Lapinte C, Haid E, Weimann G
Biochemistry. 1979 Apr 3;18(7):1212-7. doi: 10.1021/bi00574a015.
Two inhibitors of lactate dehydrogenase generated during NADH storage have been isolated by chromatography. One is a dimer of the dinucleotide where the AMP moiety is unmodified. The other is also generated from NAD+ in the presence of a high concentration of phosphate ions at alkaline pH. This inhibitor was proved to be the addition compound of one phosphate group to position C-4 of the nicotinamide ring of NAD+ by NMR spectroscopy, enzymatic cleavage, and dissociation to NAD+ at neutral pH. This compound is a competitive inhibitor with respect to NAD+ in the presence of the lactate dehydrogenase with a Ki of 2 X 10(-7) M. The interaction of this inhibitor with lactate dehydrogenase is discussed relative to the structure of this enzyme.
通过色谱法已分离出在NADH储存期间产生的两种乳酸脱氢酶抑制剂。一种是二核苷酸的二聚体，其中AMP部分未被修饰。另一种也是在碱性pH下高浓度磷酸根离子存在的情况下由NAD⁺生成的。通过核磁共振光谱、酶促裂解以及在中性pH下解离为NAD⁺，证明该抑制剂是一个磷酸基团加成到NAD⁺烟酰胺环的C-4位形成的加成化合物。在乳酸脱氢酶存在的情况下，该化合物相对于NAD⁺是一种竞争性抑制剂，其Ki为2×10⁻⁷M。结合该酶的结构对这种抑制剂与乳酸脱氢酶的相互作用进行了讨论。
