Retinoid compounds activate and induce hepatic glycine N-methyltransferase in rats.
Glycine N-methyltransferase (GNMT) functions to regulate S-adenosylmethionine (SAM) levels and the ratio of SAM/S-adenosylhomocysteine (SAH). SAM is a universal methyl group donor and the up-regulation of GNMT may lead to wastage of methyl groups required for transmethylation reactions. Previously, we demonstrated that dietary treatment of rats with 13-cis-retinoic acid (CRA) decreased the hepatic concentration of SAM and the SAH ratio. Here, we examined the ability of CRA, as well as all-trans-retinoic acid (ATRA), to regulate hepatic GNMT as a potential basis for our earlier observations. Rats were fed either a control (10% casein + 0.3% L-methionine) diet or a control diet supplemented with L-methionine (10 g/kg diet). Rats from each group were orally given ATRA, CRA (both at 30 micromol/kg body), or vehicle daily for 7 d. For control rats, administration of both CRA and ATRA elevated the hepatic GNMT activity 49% and 34%, respectively, compared with the control group. Similar results were exhibited by rats fed the methionine-supplemented diet. Moreover, the retinoid-induced elevations in enzyme activity were reflected in the abundance of GNMT protein. To our knowledge, this is the first report of a nutritional compound that induces GNMT activity at the transcriptional and/or translational level.
Rowling
M J
MJ
Department of Food Science and Human Nutrition, Iowa State University, Ames, IA 50011, USA.
Schalinske
K L
KL
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D050938:Glycine N-Methyltransferase; D008099:Liver / Q000201:enzymology*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D008715:Methionine; D008780:Methyltransferases; D050938:Glycine N-Methyltransferase; C494512:Gnmt protein, rat