formiminoglutamic-acid and formic-acid

The studies discussed in this review support the view that biochemical and clinical symptoms common to both folate and vitamin B12 deficiency are due to the induction of a functional folate deficiency, which in turn is induced by cobalamin deprivation. The interrelationship between these two vitamins is best explained by the methyl trap hypothesis stating that vitamin B12 deficiency can lead to lowered levels of methionine synthetase, which results in a functional folate deficiency by trapping an increased proportion of folate as the 5-methyl derivative. In addition, as 5-methyl-H4PteGlu is a poor substrate for folylpolyglutamate synthetase, there is a decreased synthesis of folylpolyglutamates and consequently a decreased retention of folates by tissues. The real folate deficiency that ensues because of decreased tissue folate levels is probably as important physiologically as the functional deficiency caused by the methyl trap. The sparing effect of methionine can be explained by adenosylmethionine inhibition of methylenetetrahydrofolate reductase, which would prevent the buildup of 5-methyl-H4PteGlun. A deficiency in vitamin B12 would not, in itself, be sufficient to cause a disturbance in folate metabolism. The deficiency would have to result in lowered methyltransferase levels before any such disturbance would be manifest.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Amino Acids; Animals; Bone Marrow; Folic Acid; Folic Acid Deficiency; Formates; Formiminoglutamic Acid; Histidine; Homeostasis; Humans; Liver; Megaloblasts; Methionine; Methylation; Nitrous Oxide; Peptide Synthases; Pteroylpolyglutamic Acids; Purines; Serine; Thymidine Monophosphate; Thymidylate Synthase; Thyroid Gland; Vitamin B 12; Vitamin B 12 Deficiency

The vulnerability of the nervous system due to methanol (MeOH) intoxication is a well known fact and reports on the production of free radicals due to MeOH exposure and their involvement in excitotoxicity and neuronal apoptosis are being increasingly reported. We report on MeOH induced free radical changes and oxidative damages to proteins in the discrete regions of rat brain, retina and optic nerve. The present study used rats administered with methotrexate (MTX) to induce folate deficiency. Three groups of animals, namely saline control, MTX control, MTX-MeOH group were tested. The rats were injected intraperitoneally with MeOH (3 g/kg). After 24 h of MeOH administration, the levels of free radical scavengers, superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione levels were estimated in the six discrete regions of brain (cerebral cortex, cerebellum, midbrain, pons medulla, hippocampus and hypothalamus), retina and optic nerve specimens. The levels of protein thiol, protein carbonyl and lipid peroxidation were also estimated and the expression of HSP70 in the hippocampus was analyzed by Western blot. Marked reduction in the levels of glutathione in the MTX-MeOH group in relation to MTX control was observed and found to be increased in MTX control in relation to saline control. Increased protein carbonyls and decreased protein thiols were documented in all the specimens tested. In addition, marked expression of HSP70 was observed in the hippocampus. The present investigation suggest that MeOH exposure results in increased generation of free radicals and significant protein oxidative damage and attempts to study the underlying mechanisms involved might reveal more insights to our existing knowledge on MeOH intoxication and related areas.

Topics: Animals; Brain; Catalase; Drug Therapy, Combination; Formates; Formiminoglutamic Acid; Gene Expression Regulation; Glutathione; Glutathione Peroxidase; HSP70 Heat-Shock Proteins; Lipid Peroxidation; Male; Methanol; Methotrexate; Optic Nerve; Oxidative Stress; Rats; Rats, Wistar; Retina; Sulfhydryl Compounds; Superoxide Dismutase

The chronic administration of ethanol or brief exposure to nitrous oxide (N2O) decreases the activity of hepatic methionine synthase and disrupts normal metabolic processes that require folate and vitamin B12. This combination of drugs has clinical relevance since alcoholic patients often require surgery and receive N2O as a component of their anesthetic. To assess this clinical problem using a rodent model, rats were given a liquid ethanol diet (35% of calories as ethanol) and control rats were pair-fed a liquid diet with carbohydrate substituting for the caloric content of ethanol. After receiving liquid diets for 6 weeks, rats were exposed to 60% N2O/40% O2 for 6 hr. Urinary excretions of formic acid and formiminoglutamic acid (FIGLU) were used as indirect markers of folate status. In both the ethanol-fed and control groups, excretion of formic acid and FIGLU markedly increased the first day after N2O and returned towards background values by the second day after N2O exposure. Ethanol treatment alone decreased methionine synthase activities in liver, but not kidney or brain. Exposure to N2O further decreased methionine synthase activities, and recovery of methionine synthase activity after N2O occurred over a period of 4 days at the same rate in both the ethanol-fed and control groups. Ethanol treatment for 6 weeks combined with acute exposure to N2O did not deplete the rats of vitamin B12 in blood, liver, kidney, or brain. We conclude that in this animal model, chronic treatment with ethanol does not markedly exacerbate the disturbances in folate/vitamin B12 metabolism caused by brief exposure to N2O.

Topics: 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; Alcoholism; Animals; Folic Acid; Formates; Formiminoglutamic Acid; Liver; Male; Nitrous Oxide; Rats; Rats, Inbred Strains; Vitamin B 12

Topics: Body Fluids; Folic Acid; Folic Acid Deficiency; Formates; Formiminoglutamic Acid; Glutamates; Humans