Tissue repressor concentration and target enzyme level

• Published in: Biochimica et biophysica acta Vol. 81; no. 3; pp. 435 - 441
• Main Authors: Walker, James B., Wang, Song-Hwa
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 09.03.1964
• Subjects: Acetates; Amidines; Citrulline; Creatine; Creatinine; Enzyme Inhibitors; Enzyme Repression; Ethionine; Genetics; Glycine; Guanidine; Guanidines; Liver; Methionine; OldMedline; Ornithine; Pharmacology; Proteins - metabolism; Transferases; GLYCINE; AMIDINES; ENZYME INHIBITORS; EXPERIMENTAL LAB STUDY; TRANSFERASES; CITRULLINE; CREATINE AND CREATININE; ETHIONINE; GENETICS; GUANIDINES; ORNITHINE; PHARMACOLOGY; LIVER; ACETATES; PROTEIN METABOLISM; ENZYME REPRESSION; METHIONINE
• ISSN: 0926-6569; 0006-3002; 1878-2248
• DOI: 10.1016/0926-6569(64)90128-2

Relationships between liver-creatine concentration and L-arginine: glycine amidinotransferase (EC 2.6.2.1) activity have been explored in the closed system of the developing chick embryo. Liver-creatine concentrations were increased over the endogenous level by injecting various amounts of creatine or its biosynthetic precursors into eggs on the 7th day of incubation. Embryonic livers were harvested on the 12th day and assayed for creatine and amidinotransferase activity. From these experiments a curve of liver-amidinotransferase activity vs. liver-creatine concentration was obtained. Amidinotransferase activity is markedly sensitive to creatine concentrations below 0.3 mg per g of liver; above 0.5 mg of liver there is almost complete repression. Yolk sac amidinotransferase is also repressed by injected creatine or guanidinoacetate. Factors other than the endogenous creatine level appear to be responsible for the normal 70% decline in embryonic liver-amidinotransferase activity from the 12th to 18th day of incubation. Neither the N-ethyl analogue of creatine, creatinol sulfate, nor N- amidino- DL- alanine repressed the target enzyme. Evidence is presented that guanidinoacetate represses only after conversion to creatine. Creatine, or phosphorylcreatine, appears to be the specific metabolite-repressor of amidinotransferase. An analogy of creatine with recognized hormones is suggested: creatine is synthesized by liver at a rate responsive to needs and transported via the blood to target organs, brain and muscle, where it modulates tissue function.