ERITADENINE-INDUCED ALTERATION OF HEPATIC PHOSPHOLIPID-METABOLISM IN RELATION TO ITS HYPOCHOLESTEROLEMIC ACTION IN RATS

The hypocholesterolemic effect of dietary supplementation with eritadenine, a hypocholesterolemic factor present in the Lentinus edodes mushroom, was investigated in relation to its effect on hepatic phospholipid metabolism in rats. The plasma total cholesterol level was significantly decreased by eritadenine supplementation at levels above 8 mu mol/kg of diet in a dose-dependent manner, accompanying decreases in both VLDL + LDL and HDL cholesterol levels. Eritadenine supplementation significantly increased the phosphatidylethanolamine (PE) content and inversely decreased the phosphatidylcholine (PC) content of liver microsomes in a dose-dependent manner. There was a highly significant correlation between plasma cholesterol levels and the content or proportion of PC and PE of liver microsomes. Eritadenine supplementation did not decrease the activity of PE N-methyltransferase in liver microsomes but rather increased the activity, possibly because of the increased PE content of liver microsomes. On the one hand, eritadenine had no direct inhibitory effect on the enzyme activity when added to the assay mixture. On the other hand, eritadenine supplementation increased the hepatic S-adenosylhomocysteine (SAH) level and decreased the ratio of S-adenosylmethionine (SAM) to SAH in a dose-dependent manner. The in vivo incorporation of radioactivity of [methyl-H-3]methionine into the PC of liver microsomes and blood plasma was also markedly depressed by dietary eritadenine supplementation at a level of 200 mu mol/kg of diet. These results suggest that the hypocholesterolemic action of eritadenine might be elicited through an alteration of the hepatic phospholipid metabolism that resulted from an inhibition of PE N-methylation due to a decreased SAM/SAH ratio in the liver.