Partial purification, properties and regulation of inosine 5'phosphate dehydrogenase in normal and malignant rat tissues.
IMP dehydrogenase (EC 1.2.1.14) was purified 180-fold from rat liver and from the transplantable rat hepatoma 3924A. The enzymes from the two sources were apparently identical; they exhibited hyperbolic saturation kinetics and an ordered, sequential mechanism, and were subject to inhibition by a number of purine nucleotides. Km values for the substrates, IMP and NAD+, were 12 and 24 micrometer respectively. IMP dehydrogenase activity in a spectrum of rat hepatomas was increased, relative to normal liver, by 2.5--13-fold; these increases correlated with tumour growth rate. Activity in two rat kidney tumours was increased 3-fold relative to that in normal renal cortex; control of activity of this enzyme is apparently altered in neoplastic cells. After partial hepatectomy, IMP dehydrogenase activity began to rise 6 h after operation, reaching a peak of 580% of normal activity by 18 h. Activity in neonatal liver, however, was only slightly higher than that in the adult. Organ-distribution studies showed highest enzyme activities in spleen and thymus. In livers of rats starved for 3 days, where all enzymes, except those involved in gluconeogenesis, showed decreased activity IMP dehydrogenase activity was increased; this change was accompanied by a rise in hepatic GTP concentrations. It is concluded that IMP dehydrogenase is a key enzyme in the regulation of GTP production, and thus involved in regulation of nucleic acid biosynthesis. The increased activity of IMP dehydrogenase in liver of starved rats may be related to the requirements for GTP for gluconeogenesis.
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D003956:Dialysis; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors / Q000302:isolation & purification*; D007658:Ketone Oxidoreductases / Q000302:isolation & purification*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008113:Liver Neoplasms / Q000201:enzymology*; D008115:Liver Regeneration; D009243:NAD / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000201:enzymology; D051381:Rats; D013217:Starvation / Q000201:enzymology; D013963:Thyroid Hormones / Q000494:pharmacology
D013963:Thyroid Hormones; D009243:NAD; D007168:IMP Dehydrogenase; D007658:Ketone Oxidoreductases