formiminoglutamic-acid and Starvation

Formiminoglutamate (FIGLU) urinary excretion was studied in rats subjected to whole body 60Co irradiation with doses of 450, 650 and 850 R. During the first post-irradiation days, FIGLU excretion doubled after both lower doses. From day 3, 450 R led to a decrease, whereas 650 and 850 R were followed by a still enhanced FIGLU excretion. No correlation to the radiation dose was found. A daily intraperitoneal administration of histidine in a dose of 200 mg/kg led to a constant 5-fold increase of FIGLU output and to more distinct differences in post-irradiation FIGLU excretion. Two days starvation or ACTH administration, followed by doubled urinary total 17-hydroxycorticoids, did not interfere with FIGLU excretion.

Topics: Animals; Cobalt Radioisotopes; Formiminoglutamic Acid; Glutarates; Histidine; Male; Radiation Injuries; Rats; Starvation; Stress, Physiological

1. The isolated perfused rat liver and suspensions of isolated rat hepatocytes fail to form glucose from histidine, in contrast with the liver in vivo. Both rat liver preparations readily metabolize histidine. The main end product is N-formiminoglutamate. In this respect the liver preparations behave like the liver of cobalamin- or folate-deficient mammals. 2. Additions of L-methionine in physiological concentrations (or of ethionine [2-amino-4-(ethylthio)butyric acid]) promotes the degradation of formiminoglutamate, as is already known to be the case in cobalamin of folate deficiency. Added methionine also promotes glucose formation from histidine. 3. Addition of methionine accelerates the oxidation of formate to bicarbonate by hepatocytes. 4. A feature common to cobalamin-deficient liver and the isolated liver preparations is taken to be a low tissue methionine concentration, to be expected in cobalamin deficiency through a decreased synthesis of methionine and caused in liver preparations by a washing out of amino acids during the handling of the tissue. 5. The available evidence is in accordance with the assumption that methionine does not directly increase the catalytic capacity of formyltetrahydrofolate dehydrogenase; rather, that an increased methionine concentration raises the concentration of S-adenosylmethionine, thus leading to the inhibition of methylenetetrahydrofolate reductase activity [Kutzbach & Stokstad (1967) Biochim. Biophys. Acta 139, 217-220; Kutzbach & Stokstad (1971) Methods Enzymol. 18B, 793-798], that this inhibition causes an increase in the concentration of methylenetetrahydrofolate and the C1 tetrahydrofolate derivatives in equilibrium with methylenetetrahydrofolate, including 10-formyltetrahydrofolate; that the increased concentration of the latter accelerates the formyltetrahydrofolate dehydrogenase reaction, because the normal concentration of the substrate is far below the Km value of the enzyme for the substrate. 6. The findings are relevant to the understanding of the regulation of both folate and methionine metabolism. When the methionine concentration is low, C1 units are preserved by the decreased activity of formyltetrahydrofolate dehydrogenase and are utilized for the synthesis of methionine, purines and pyrimidines. On the other hand when the concentration of methionine, and hence adenosylmethionine, is high and there is a surplus of C1 units as a result of excess of dietary supply, formyltetrahydrofolate dehydroge

Topics: Amino Acids; Animals; Carbon Dioxide; Folic Acid; Formates; Formiminoglutamic Acid; Glucose; Glutamates; Histidine; In Vitro Techniques; Liver; Methionine; Rats; Starvation; Urocanic Acid