Altered metabolism of folates and lipids in hyperthyroid and hypothyroid rats.

Effect of excess folate on the metabolism of folate and plasma lipids in thyroid stressed animals was studied. Administration of excess dietary folate to hyperthyroid rats did not affect the decreased in vivo histidine oxidation in these animals, but it increased the hepatic tetrahydrofolate content. Hypothyroid rats had higher plasma total cholesterol (TC), high density lipoprotein cholesterol (HDLC) and trigylcerides (TG) with no change in post heparin lipolytic activity (PHLA). In hyperthyroidism both TC and HDLC were decreased in plasma and PHLA levels were elevated. On administration of excess dietary folate to hyperthyroid rats HDLC levels were not altered but PHLA and TC levels became near normal, while TG levels remained elevated.

Possible involvement of superoxide radical in biochemical lesions induced by nitrous oxide.

Inactivation of methionine synthase (MS) by nitrous oxide (N2O) administration to animals and man has been postulated to be mediated by hydroxyl radical (OH). An alternate mechanism has been proposed which involves superoxide radical (O2.-) originating from N2O in the inactivation of MS by OH that may arise from O2.- through Fenton/Haber-Weiss reaction. Rats inhaling a mixture of N2O:O2 (1:1) for 5 hr showed inactivation of MS in liver to nearly 90% which could not be reversed by prior administration of either dimethyl sulfoxide (DMSO) or sodium benzoate. Pretreatment of rats with superoxide dismutase (SOD) at two doses, 0.1 mg and 3.5 mg/100 g body weight, retarded the in vivo inactivation of MS by N2O, to 76% and 47% respectively. In vitro inactivation of MS with N2O could not be retarded by DMSO or Na-benzoate, or either exogenous SOD or catalase.

Folylpolyglutamate synthetase in Lactobacillus leichmannii: in vitro synthesis and characterization of polyglutamylfolates.

In vitro synthesis of folylpolyglutamates by folylpolyglutamate synthetase from Lactobacillus leichmannii has been studied and optimal conditions for enzyme activity determined. It is found that while ATP (5 mM) is essential for the synthesis of folylpolyglutamates homocysteine augments the same. Replacement of vitamin B12 (2 ng/ml) with deoxyuridine (20 micrograms/ml) in growth medium does not alter the enzymatic parameters studied. DEAE-cellulose column chromatography of in vitro synthesised folylpolyglutamates indicates that folylpolyglutamate synthetase of L. leichmannii can synthesize polyglutamates up to a chain length of four glutamate residues.

Effect of nitrous oxide and methionine on hepatic S-adenosylmethionine levels and in vivo histidine oxidation in rats.

Nitrous oxide (N2O) decreased in vivo oxidation of histidine in rats fed a basal diet marginally deficient in methionine, although hepatic levels of S-adenosylmethionine (AdoMet) were not significantly altered. Excess dietary methionine increased hepatic levels of AdoMet and increased histidine oxidation. However, it did not protect histidine oxidation when the rats were treated with N2O. Parenteral administration of methionine greatly increased hepatic levels of AdoMet and increased histidine oxidation in normal and N2O treated rats. This indicates that when hepatic levels of AdoMet are greatly elevated by administration of methionine, N2O does not affect in vivo histidine oxidation.

An indirect role of vitamin B12 in regulation of thymidylate synthase in Lactobacillus leichmannii.

Vitamin B12 augments thymidylate synthase function in L. leichmannii by facilitating indirectly the availability of suitable nonmethylpolyglutamylfolate cofactors. This is effected by the demethylation of trapped methyltetrahydrofolates, catalysed by a vitamin B12 requiring methionine synthase. Deoxyuridine supplemented cells, lacking in B12, have decreased levels of methionine synthase and thymidylate synthase. Addition of active and inactive conjugase preparation as a source of mono and polyglutamylfolates indicated that the latter are the preferred cofactors for thymidylate synthase.