Novel S-adenosylmethionine-dependent indole-N-methylation of beta-carbolines in brain particulate fractions.
Novel S-adenosylmethionine-dependent indole-N-methylation of beta-carbolines in brain particulate fractions.
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脑颗粒部分中β-咔啉的新型S-腺苷甲硫氨酸依赖性吲哚-N-甲基化。
DOI：
10.1111/j.1471-4159.1992.tb09400.x
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发表时间：
1992
影响因子：
4.7
通讯作者：
Collins,MA
中科院分区：
文献类型：
--
作者：
Matsubara,K;Neafsey,EJ;Collins,MA
Guinea pig brain S‐adenosylmethionine (SAM)‐dependentN‐methyltransferase activity toward physiologically relevant β‐carboline (BC) substrates was examined with reverse‐phase HPLC and radiochemical detection. Representative BCs, norharman and harmine, were enzymatically methylated on the 2[β]‐nitrogen by [3H]CH3‐SAM in undialyzed homogenates to yield 2[β]‐methylated BCs and subsequently on the 9[indole]‐nitrogen to generate 2,9‐dimethylated BC products. This may be the first account of mammalian indoleN‐methyl transfer. There was no HPLC evidence for 9‐methyl BC or (from carbon methylation) 2,6‐dimethyl BC products. Capillary gas chromatography‐mass spectrometry analysis confirmed the structures of the 2,9‐dimethyl and 2‐methyl products of norharman. The 2[β]‐ and 9[indole]‐N‐methylation activities were mainly in the nuclear fractions and were negligible in undialyzed cytosol. This differs from the cytosolic SAM‐dependentN‐methylations reported with other azaheterocyclics, including 1,2,3,4‐tetrahydro‐BCs. The involvement of a single enzyme was suggested because the twoN‐methyl transfers with BC substrate had similar subcellular activity patterns, regional brain distributions, and Kmand Vmaxvalues. SequentialN‐methylation of various BCs that have been observed in vivo may be a unique route to centrally retained N2,N9‐dimethylated β‐carbolinium ions. Because they resemble the synthetic parkinsonian toxicant,N‐methyl‐4‐phenylpyridinium, with respect to structure and neurotoxic activity, such “bioactivated” carbolinium ions could be endogenous causative factors in Parkinson's disease.
