Transmethylation pathway: aberrancy in methyltransferase reactions in diet-induced NAFLD.

<p>(A) Heat map representation of substrates and methylated products of major SAM-derived transmethylation reactions (PEMT, GNMT, GAMT and PRMT) with HFHC diet for 52 weeks. (B) Levels of glycine, a substrate for GNMT, were decreased (p< 0.01) while the product sarcosine did not change between chow and HFHC group. (C) The gene expression of <i>Gnmt</i>, the most abundant methyltranserase in the liver, decreased significantly but only approached significance at the protein level (p = 0.06). (D) Levels of PE, the substrate for PEMT, was significantly reduced (p< 0.01) while PC trended down, resulting in a significant PC/PE ratio (p< 0.01), which suggests increase in PEMT activity There were no significant changes in the concentrations of guanidinoacetate and creatine, the substrate and product for GAMT, respectively. (E) The methylated products of PRMT activity, MMA and ADMA, were decreased significantly (p< 0.01 and p< 0.05) while the decrease in SDMA approached significance (p = 0.07). (F) The gene expression of <i>Prmt1</i>, mainly responsible for the methylation of MMA and ADMA, decreased (p< 0.01) but the protein levels of PRMT1 increased significantly (p< 0.05). (G) Circulating ADMA was increased toward significance (p = 0.06), suggesting increased export to the circulation. Data are represented as mean ± SEM. Legend: arginine (Arg); asymmetric dimethylarginine (ADMA); creatine (Crea); glycine (Gly); glycine N-methyltransferase (GNMT); guanidinoacetate (GAA); guanidinoacetate methyltransferase (GAMT); homocysteine (Hcy); monomethylarginine (MMA); phosphatidylcholine (PC); phosphatidylethanolamine (PE); phosphatidylethanolamine methyltransferase (PEMT); protein arginine methyltransferase (PRMT); s-adenosylhomocysteine (SAH); s-adenosylmethionine (SAM); sarcosine (Sar); symmetric dimethylarginine (SDMA).