Activation and induction of glycine N-methyltransferase by retinoids are tissue- and gender-specific.

Glycine N-methyltransferase (GNMT) is a key protein in the liver that functions to regulate S-adenosylmethionine (SAM) and the SAM/S-adenosylhomocysteine ratio. Significant GNMT expression is also present in the kidney and pancreas. Inappropriate regulation of GNMT may have negative consequences on methyl group and folate metabolism. We have demonstrated that retinoid compounds significantly elevated hepatic GNMT activity and abundance (approximately 2-fold) in male rats. However, pancreatic GNMT activity and abundance were not altered by retinoid treatment. Likewise, retinoid administration was without effect on renal GNMT activity. Hepatic GNMT activity was also elevated in female rats treated with all-trans-retinoic acid, but to a lesser extent compared to males. Collectively, these results indicate that the modulation of methyl group metabolism by retinoids is tissue- and gender-specific, and may compromise the availability of methyl groups for SAM-dependent transmethylation reactions. In support of this, SAM-dependent synthesis of creatinine was significantly reduced 21% following all-trans-retinoic acid treatment.