INFLUENCE OF METHIONINE AVAILABILITY ON GLUTATHIONE SYNTHESIS AND DELIVERY BY THE LIVER

The aim of this study was to define dietary conditions liable to eleva te the circulating and tissue levels of glutathione (GSH). For this pu rpose, GSH synthesis and availability have been compared after supplem entation of a low protein diet (10% casein) with 0.6% methionine or af ter adaptation to a high protein diet (30% casein), the final dietary methionine levels were similar in both cases. To compare the effects o f an acute addition of sulfur amino acids to the diet with long-term a daptative changes on GSH status, rats adapted to the 10% casein diet r eceived as a final meal (i) the diet supplemented with 0.6% methionine or (ii) a 30% casein diet. With a 10% casein diet, the plasma and tis sue concentrations of methionine and cysteine seem to constitute limit ing factors for GSH synthesis. However, in animals adapted to a high p rotein diet or to a diet supplemented in methionine, the hepatic GSH c ontent was quite enhanced (respectively 1.9 and 2.6 fold that measured in the control diet), in keeping with the marked rise of the hepatic cysteine (respectively 2 and 5 fold that measured in the control diet) . Acute administration of a final 30% casein meal or 10% casein meal s upplemented in methionine induced greater changes in the hepatic GSH c ontent than observed in long-term experiments. Compared with the liver , the muscle and heart GSH content was poorly affected by changes in s ulfur amino acids availability or nutritional state. The liver appears as a net site of GSH release, the magnitude of this release was not e ntirely proportional to the hepatic pool, particularly during the post absorptive period. Moreover, during this period the hepatic GSH conten t was markedly depressed compared with the fed state, whatever the die tary conditions. With diets providing a high availability in sulfur am ino acids, the activity of the liver gamma-glutamyl cysteine synthetas e was markedly depressed, even in acute experiments. In vitro experime nts confirmed in vivo results, and showed that until its extracellular concentration reached 0.4 mM, methionine may constitute a limiting fa ctor for GSH synthesis in isolated hepatocytes. (C) Elsevier Science I nc. 1997.