Methyl group partitioning during insufficient and excess availability via guanidinoacetate and creatine supplementation in young pigs

Abstract

Methionine is an essential amino acid that provides methyl groups for transmethylation (TM) reactions via S‐adenosylmethionine (SAM), resulting in S‐adenosylhomocysteine (SAH), an inhibitor of TM reactions. Methylation of guanidinoacetate (GAA) to produce creatine (Cr) is proportional to GAA availability while Cr supplementation reduces GAA production and spares methyl groups. Our objective was to determine the partitioning of methyl groups among TM reactions under conditions of excess and insufficient methyl group availability. Three mo‐old pigs (n=18) were fed control, GAA‐ or Cr‐supplemented diets twice daily. On day 18, anesthesia was induced 1–3 h post feeding and a bolus of [methyl‐3H]methionine was intravenously infused. After 30 min, the liver was analyzed for methyl‐3H incorporation into protein, Cr, phosphatidylcholine (PC) and DNA. Compared to control (P<0.05), Cr and GAA led to a 200% and 700% increase in hepatic Cr concentration, respectively; GAA caused a 400% increase in total hepatic Cr methyl‐3H incorporation. Unlike Cr pigs, GAA supplementation decreased methyl‐3H incorporation into PC and decreased hepatic SAM concentration with no change in SAH, suggesting that creatine synthesis resulted in a limited methyl supply for PC synthesis (P<0.05). Creatine supplementation did not spare methyl groups, but GAA did lead to a limited methyl supply (CIHR).Grant Funding Source: CIHR