Biosynthesis of Methylguanidine in the Hepatic Microsomal Fraction
作者:
Sohji Nagase,
Kazumasa Aoyagi,
Masako Sakamoto,
Katsumi Takemura,
Toshiko Ishikawa,
Mitsuharu Narita,
期刊:
Nephron
(Karger Available online 1992)
卷期:
Volume 62,
issue 2
页码: 182-186
ISSN:1660-8151
年代: 1992
DOI:10.1159/000187030
出版商: S. Karger AG
关键词: Methylguanidine;Microsome;Mixed function oxidase;P-450;Active oxygen
数据来源: Karger
摘要:
We have investigated various synthetic mechanisms for the production of methylguanidine, a potent uremic toxin, and reported a role for active oxygen in its biosynthesis from creatinine in studies using isolated hepatocytes. In this study, we turn our attention to the hepatic microsomes. Liver homogenates were made from rats, and various organelles were obtained by centrifugation and incubated with creatinine. The results show that methylguanidine synthesis occurs only in the microsomal fraction in the presence of nicotinamide adenine dinucleotide phosphate, reduced form. The microsomal activity is inhibited by the addition of methimazole, metyrapone, superoxide dismutase, catalase or dimethylsulfoxide. These results suggest that methylguanidine is synthesized from creatinine by microsomes, and at least 2 enzymes are involved, an FAD-containing monooxygenase and a P-450-dependent oxidase based on the inhibitory effect of methimazole and metyrapone, respectively. Moreover, the inhibition by various scavengers of active oxygen suggests that active oxygen plays a role in the intermediate steps of the enzymatic reaction.
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