Increased plasma homocysteine and S-adenosylhomocysteine and decreased methionine is associated with altered phosphatidylcholine and phosphatidylethanolamine in cystic fibrosis

Abstract

ObjectiveWe used a novel approach based on the intersection of phospholipid and methionine metabolism at the S-adenosylmethionine (SAM)-dependent methylation of phosphatidylethanolamine (PE) to study potential alterations in phospholipid metabolism in children with cystic fibrosis (CF). Methyl groups from methionine via SAM are used for sequential methylation of PE to form phosphatidylcholine (PC) with the generation of S-adenosylhomocysteine (SAH) and homocysteine. Study designPlasma phospholipids and methionine metabolites and plasma and red blood cell phospholipid fatty acids were determined in 53 children with CF and 18 control children. ResultsPlasma methionine and the PC/PE ratio was lower and homocysteine, SAH, and PE were higher in children with CF than in control children (P<.001). Plasma methionine was inversely (P<.05) and SAH and homocysteine were positively (P<.001) correlated with the plasma PE. Docosahexaenoic acid (22:6n-3) was significantly lower in plasma phospholipids and triglycerides and in red blood cell PC and PE of children with CF than in control children (P<.05). ConclusionsThese studies demonstrate that methionine metabolism is altered and associated with alteration of the plasma PC/PE ratio in CF. Altered phospholipid and methionine metabolism may contribute to the clinical complications associated with CF.