Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The intracellular distribution of N-methyl-transferase requiring 5-methyl-tetrahydrofolic acid (5 MT-NMT) was studied in brain, kidney and liver of rats. Among these different tissues, the kidney displayed the highest enzyme activity, more than 20 times the activity detected in the brain. As the striatum and, to a lesser extent the hypothalamus, were found to contain slightly higher 5 MT-NMT than other cerebral regions, they were also selected for the study of the subcellular localization. Tissue fractionation was performed by differential centrifugation yielding five different fractions which were analyzed for their enzymatic content not only of 5 MT-NMT but also of marker enzymes, such as cytochrome oxidase, acid phosphatase and inosine diphosphatase. In all the tissues studied, 5 MT-NMT was recovered in the supernatant fraction. Therefore one may consider this enzyme to belong to the cytosol. Although a neuronal localization cannot be excluded, it is beyond doubt that the enzyme is contained in other cellular types. In the brain fractionation, the five fraction procedure seems to be very useful especially when the subcellular distribution of a given enzyme is compared to that obtained in other tissues like liver or kidney. Finally 5 MT-NMT may be considered a good marker enzyme for the supernatant fraction.
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PMID:Tissue fractionation in rat brain, kidney and liver. I. Intracellular localization of a 5-methyltetrahydrofolic acid requiring enzyme. 16 5

We hypothesized that the unanticipated bioactivity of orally administered unnatural carbon-6 isomers, (6R)-5-formyltetrahydrofolate (5-HCO-THF) and (6S)-5,10-methenyltetrahydrofolate (5,10-CH-THF), in humans [Baggott, J. E., and Tamura, T. (1999) Biochim. Biophys. Acta 1472, 323-32] is explained by the rapid oxidation of (6S)-10-formyltetrahydrofolate (10-HCO-THF), which is produced by in vivo chemical processes from the above folates. An oxidation of 10-HCO-THF produces 10-formyldihydrofolate (10-HCO-DHF), which no longer has the asymmetric center at carbon-6 and is metabolized by aminoimidazole carboxamide ribotide (AICAR) transformylase forming bioactive dihydrofolate. Since cytochrome c (Fe(3+)) rapidly oxidizes both (6R)- and (6S)-10-HCO-THF [Baggott et al. (2001) Biochem. J. 354, 115-22], we investigated the metabolism of 10-HCO-THF by isolated rat liver mitochondria. We found that 10-HCO-THF supported the respiration of mitochondria without uncoupling ATP synthesis. The site of electron donation was identified as complex IV, which contains cytochrome c; the folate product was 10-HCO-DHF, and the reaction was saturable with respect to 10-HCO-THF. Both (6S)- (unnatural) and (6R)-10-HCO-THF supported the respiration of mitochondria, whereas (6S)-5-formyltetrahydrofolate (5-HCO-THF) was inactive. To our knowledge, this cytochrome c oxidation of 10-HCO-THF to 10-HCO-DHF in the mitochondrial intermembrane space represents a possible folate metabolic pathway previously unidentified and would explain the bioactivity of unnatural carbon-6 isomers, (6R)-5-HCO-THF and (6S)-5,10-CH-THF, in humans.
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PMID:Oxidation of 10-formyltetrahydrofolate to 10-formyldihydrofolate by complex IV of rat mitochondria. 1196 24

Acute methanol poisoning is mainly the consequence of voluntary or accidental ingestion. The mortality and morbidity rates remain very high despite intensive care therapy. Methanol by itself is poorly toxic. Methanol is transformed in the liver into formaldehyde and thereafter formic acid. Metabolic acidosis is the main biological feature of poisoning. Acidosis is related to formic acid accumulation, and also to a less extent to lactate production. In contrast to rodents, primates are relatively deficient in tetrahydrofolate reductase and therefore formic acid is usually the final metabolite. Formic acid is able to inhibit cytochrome oxidase activity in the mitochondria, leading to histotoxic hypoxia. The most sensitive organs to the effects of formic acid are the brain and the visual pathway, while other organs may also be seriously damaged according to the severity of metabolic acidosis. Hemodialysis remains indicated for the removal of both methanol and formic acid. Fomepizole is a recently approved antidote. It appears safe and effective. Analysis of its cost-effectiveness ratio is still ongoing in methanol poisoning.
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PMID:[Acute methanol intoxication: physiopathology, prognosis and treatment]. 1728 75