A N-methyltransferase in human brain catalyses N-methylation of 1,2,3,4-tetrahydroisoquinoline into N-methyl-1,2,3,4-tetrahydroisoquinoline, a precursor of a dopaminergic neurotoxin, N-methylisoquinolinium ion.
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.
Naoi
M
M
Department of Biochemistry, Nagoya University School of Medicine, Japan.
Matsuura
S
S
Takahashi
T
T
Nagatsu
T
T
D002540:Cerebral Cortex / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007546:Isoquinolines / Q000302:isolation & purification* / Q000378:metabolism*; D007700:Kinetics; D008780:Methyltransferases / Q000378:metabolism*; D009498:Neurotoxins; D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D009498:Neurotoxins; D044005:Tetrahydroisoquinolines; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; C014843:1,2,3,4-tetrahydroisoquinoline; D008780:Methyltransferases