Enzymes of the gamma-glutamyl cycle are programmed in utero by maternal nutrition.

Exposing the rat fetus to maternal low-protein diets during gestation has been shown to programme a number of metabolic and physiological changes. The present study examines the effects of maternal dietary manipulation upon glutathione cycle enzymes in the rat. Pregnant rats were fed either a non-purified chow diet or purified diets containing 18, 9 or 6% casein. Enzyme activities in the resulting offspring were determined at 4 weeks of age. Weanling pups exposed to the chow diet in utero had significantly lower activities of the glutathione synthetic enzyme gamma-glutamylcysteine synthetase in liver and lung than rats exposed to purified diets. Glutathione peroxidase activity in the liver also tended to be lower in these animals. Glutathione reductase activity in liver was negatively correlated with maternal protein intake, with rats exposed to 6% casein in utero having a significantly raised activity of this recycling enzyme, relative to controls exposed to 18% casein. These data are consistent with the hypothesis that components of maternal diet, including the level of protein intake, programme glutathione cycle enzymes, or production of their regulatory elements, in utero.