Naoi M, Matsuura S, Takahashi T, Nagatsu T
Department of Biochemistry, Nagoya University School of Medicine, Japan.
Biochem Biophys Res Commun. 1989 Jun 30;161(3):1213-9. doi: 10.1016/0006-291x(89)91371-5.
N-methylation of 1,2,3,4-tetrahydroisoquinoline (TIQ) present in human brain was found by a N-methyltransferase in human brain homogenate. Formation of N-methyl-1,2,3,4-tetrahydroisoquinoline (NMTIQ) from TIQ was quantitatively assayed by high-performance liquid chromatography with electrochemical detection. The reaction required S-adenosyl-L-methionine (SAM) as a methyl donor and in terms of SAM the value of the Michaelis constant, Km, and of the maximal velocity, Vmax, were 5.11 +/- 1.69 microM and 7.31 +/- 0.21 pmol/min/mg protein, respectively. The value of Km and Vmax in terms of TIQ were 20.9 +/- 5.5 microM and 7.98 +/- 1.21 pmol/min/mg protein, respectively. The optimal pH of the reaction was 8.25. A major part of the N-methyltransferase activity was found in the cytosolic fraction of human cortex. Enzymatic formation of NMTIQ indicates that in human brain this compound may be an intermediate of biosynthesis of a potent neurotoxin of dopamine metabolism, N-methylisoquinolinium ion, from naturally-occurring TIQ.
人脑海马体匀浆中的一种N-甲基转移酶可催化人脑中1,2,3,4-四氢异喹啉（TIQ）发生N-甲基化。通过高效液相色谱-电化学检测法定量测定TIQ生成N-甲基-1,2,3,4-四氢异喹啉（NMTIQ）的反应。该反应需要S-腺苷-L-甲硫氨酸（SAM）作为甲基供体，就SAM而言，米氏常数Km和最大反应速度Vmax分别为5.11±1.69μM和7.31±0.21 pmol/min/mg蛋白质。就TIQ而言，Km和Vmax的值分别为20.9±5.5μM和7.98±1.21 pmol/min/mg蛋白质。反应的最适pH为8.25。N-甲基转移酶活性的主要部分存在于人脑皮质的胞质组分中。NMTIQ的酶促形成表明，在人脑中，该化合物可能是天然存在的TIQ生物合成一种强效多巴胺代谢神经毒素N-甲基异喹啉离子的中间体。
