Tamaki N, Kubo K, Aoyama H, Funatsuka A
J Biochem. 1983 Apr;93(4):955-9. doi: 10.1093/oxfordjournals.jbchem.a134250.
Among uracil derivatives investigated, 6-azauracil, 6-azathymine, and 5-iodouracil were found to be potent inhibitors of purified rabbit liver 4-aminobutyrate aminotransferase while 6-azauridine and 6-azauridine 5'-phosphate were not. The enzyme inhibited by 6-azauracil was reactivated by dialysis but not by addition of pyridoxal 5'-phosphate. 6-Azauracil acted as a non-competitive inhibitor with respect to beta-alanine as well as 2-oxoglutaric acid, and had a K1 of approximately 0.7 mM at pH 7.3. The kinetic data suggested that 2-oxoglutaric acid acted as an inhibitor as well as an amino acceptor for the enzyme; a catalytic site was associated with an apparent Km of 0.15 mM for 2-oxoglutaric acid and a low affinity site was associated with an I50 of approximately 5 mM for the 2-oxo acid. With inhibitory concentrations of 2-oxoglutaric acid as substrate the inhibitory effect of 6-azauracil was considerably diminished. From these findings, the inhibitory effect of 6-azauracil was revealed to be different from that of structural analogs of 4-aminobutyric acid showing that 6-azauracil is a new type of 4-aminobutyrate aminotransferase inhibitor.
在所研究的尿嘧啶衍生物中，发现6-氮杂尿嘧啶、6-氮杂胸腺嘧啶和5-碘尿嘧啶是纯化兔肝4-氨基丁酸转氨酶的有效抑制剂，而6-氮杂尿苷和6-氮杂尿苷5'-磷酸则不是。被6-氮杂尿嘧啶抑制的酶通过透析可重新激活，但添加磷酸吡哆醛5'-磷酸则不能。6-氮杂尿嘧啶对β-丙氨酸和2-氧代戊二酸均表现为非竞争性抑制剂，在pH 7.3时其Ki约为0.7 mM。动力学数据表明，2-氧代戊二酸既是该酶的抑制剂又是氨基受体；一个催化位点与2-氧代戊二酸的表观Km为0.15 mM相关，一个低亲和力位点与该2-氧代酸的I50约为5 mM相关。以抑制浓度的2-氧代戊二酸作为底物时，6-氮杂尿嘧啶的抑制作用明显减弱。从这些发现可知，6-氮杂尿嘧啶的抑制作用与4-氨基丁酸的结构类似物不同，表明6-氮杂尿嘧啶是一种新型的4-氨基丁酸转氨酶抑制剂。
