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Nutritional Significance of Increase in -Glutamyltransferase in Mouse Liver before Birth¹

Department of Biochemistry, Institute for Cancer Research, Osaka University Medical School, 1-1-50, Fukushima-ku, Osaka 553, Japan

The level of glutathione increases in fetal mouse liver during gestation. The increase stops at less than half the adult level just before birth and then continues steadily after birth. The level of cysteine increases just before birth and decreases gradually after birth, although its apparent change is much less than that of glutathione. Glutathione-synthesizing enzymes increase slowly throughout the perinatal period. On the contrary, activity of the glutathione-degrading enzyme, -glutamyltransferase (-GT, EC 2.3.2.2.) in fetal mouse liver increases rapidly just before birth, reaching a maximum at birth and then decreasing rapidly within 1 week after birth to nearly the level in adult liver. The more rapid increase of -GT activity than of the activities of glutathione-synthesizing enzymes appears to cause the temporary pause in the increase in glutathione. The temporary, but significant, increase of -GT in mouse liver at birth was analyzed to determine the role of the enzyme in nutritional adaptation of animals during this critical period of life. Tracer studies using [³⁵S]cysteine showed that in the last part of fetal life, cysteine is transferred preferentially from the dams to the fetuses for protein synthesis. At the same time, cysteine is mobilized from glutathione in the fetal liver for the same purpose. The significant increase of fetal hepatic -GT must be responsible for mobilizing the cysteine moiety of liver glutathione.

KEY WORDS: • fetal liver glutathione • fetal liver cysteine • -glutamyltransferase • glutathione-synthesizing enzymes • liver protein synthesis

¹ Part of this work was presented orally at the 1st FAOB Congress in October 1977 in Nagoya, Japan (abs. No. FP 45) and the 3rd Joint Meeting of the AIN-ASCN-NSC in July 1979 in Guelph, Canada (abs. No. 42).

Manuscript received 31 August 1979.