By Ronald W. Estabrook and Paul Srere (Eds.)
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The very low concentration of glutathione in the blood plasma shows that glutathione is effectively removed from the circulation. Glutathionuria induced by administration of transpeptidase inhib itors seems to provide an experimental animal model for the human disease in which there is deficiency of transpeptidase activity. In the absence of the enzyme, or when the enzyme is inhibited, glutathione is translocated out of renal cells. It is reasonable to infer that under normal conditions in which the enzyme is active, translocated renal glutathione serves as a substrate of the transpeptidase.
55. , Biochem. Biophys. Res. Commun. 71, 1118-1124 (1976). 56. , and Cohen, P. , J. Biol. Chem. 247, 1641-1653 (1972). THE ORNITHINE-UREA CYCLE 17 57. , and Cohen, R R, J. Biol. Chem. 247, 1654-1668 (1972). 58. , and Cohen, P. , J. Biol. Chem. 247, 1669-1672 (1972). 59. , in "The Urea Cycle" (S. Grisolia, R. ), pp. 169-179. Wiley, New York, 1976. 60. Pierson, D. , Cox, S. , and Gilbert, B. E . , J . Biol. Chem. 252, 6464-6469 (1977). 61. Kalousek, F , Baudoin, F , and Rosenberg, L. , J. Biol. Chem.
Le Van, S. , Trend, B. , and Russell, L. , Proc. NatL Acad. Sei. A. 73, 1693-1697 (1976). DISCUSSION Dr. Lane: Do you know what the rate-limiting step is in the cycle? Dr. Cohen: Argininosuccinate synthetase activity is of the same order as that of carbamyl phosphate synthetase. However, because CPS I represents the initial step in urea biosynthesis, this step can be considered to be rate-limiting under normal conditions. THE ORNITHINE-UREA CYCLE 19 Dr. Hastings: Have you noticed any oircadian cycle modulation in the activity or synthesis of the enzymes?