Diabetes and all-trans-retinoic acid (ATRA) have been shown to disrupt methyl group metabolism, including a decrease in homocysteine concentrations due to elevated expression of the folate-independent enzyme betaine-homocysteine S-methyltransferase (BHMT) and stimulation of the folate-dependent enzyme methionine synthase, respectively. Phosphatidylcholine (PC) is an essential phospholipid that can be synthesized by either the CDP-choline pathway or S-adenosylmethionine (SAM)-dependent methylation of phosphatidylethanolamine by phosphatidylethanolamine N-methyltransferase (PEMT). It has recently been suggested that PEMT is the major consumer of hepatic methyl groups and thus is a key contributor to elevated plasma homocysteine levels, an independent risk factor for cardiovascular disease. We investigated how diabetes and ATRA, both individually and in combination, affect SAM-dependent phospholipid methylation. Rats received a single injection of streptozotocin (STZ, 60 mg/kg body weight) or vehicle followed by administration of ATRA (30 μmol/kg body weight) or vehicle for 5 d. Diabetes increased the hepatic activity of PEMT 50%, whereas ATRA supplementation was without affect. Although PC concentrations were not altered, the proportion of PC (% total phospholipids) was increased in all treatment groups. Plasma homocysteine concentrations were decreased 30-35% in all treatment groups as compared to control values. Thus, diabetes-mediated alterations in PEMT activity were not directly correlated to plasma homocysteine levels or PC concentrations. Taken together, the increase in PEMT as well as BHMT may indicate an increased requirement for choline in the diabetic state. (Support: Am. Diabetes Assoc.)
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