S-methylation of diethyldithiocarbamic acid in rat liver microsomes

Article abstract of DOI:10.3109/00498259609167420

1. Human hepatic thiol methyltransferase (TMT) is a microsomal enzyme known to catalyse the in vitro S-methylation of diethyldithiocarbamic acid (DDC) to form diethyldithiocarbamic acid methyl ester (methyl DDC). In vivo data are needed to investigate further the biotransformation of DDC to methyl DDC. Thus, we have characterized the in vitro conversion of DDC to methyl DDC using rat liver microsomes with the ultimate goal of establishing an animal model. 2. Formation of methyl DDC in rat liver microsomes was confirmed by hplc analysis. 3. Rat liver microsomes catalysed methylation of DDC with low and high K(m)'s of 5 ± 6 and 260 ± 80 μM respectively and with corresponding V(max)'s of 0.09 ± 0.05 and 0.59 ± 0.04 nmol/min/mg protein. 4. Rat liver TMT activity was maximally inhibited by 57 ± 6% by 1000 μM 2,3-dichloro-α-methylbenzylamine (DCMB), whereas human TMT was completely inhibited. The concentration of half maximal inhibition of rat TMT for DCMB was 2 μM. 5. Incomplete inhibition of rat TMT activity by DCMB suggests a possible alternative pathway of methylation.

Full text of DOI:10.3109/00498259609167420

Xenobiotica
the fate of foreign compounds in biological systems
ISSN: 0049-8254 (Print) 1366-5928 (Online) Journal homepage: http://www.tandfonline.com/loi/ixen20
S-methylation of diethyldithiocarbamic acid in rat
liver microsomes
J. S. Lill, D. C. Mays & J. J. Lipsky
To cite this article: J. S. Lill, D. C. Mays & J. J. Lipsky (1996) S-methylation of
diethyldithiocarbamic acid in rat liver microsomes, Xenobiotica, 26:10, 1025-1033
To link to this article: http://dx.doi.org/10.3109/00498259609167420
Published online: 27 Aug 2009.
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Date: 05 November 2015, At: 14:39