Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02011 (FAD)
 5,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The thiourea insecticide/acaricide diafenthiuron represents a biologically inactive propesticide that requires transformation into the active carbodiimide derivative. The carbodiimide inhibits mitochondrial respiration by selective and covalent binding to the proteolipid (8 kDa) of Fo-ATPase in the inner membrane and to porin (30 kDa) in the outer membrane. The thiourea can be activated by light as well as by cytochrome P450 in the insect. To get insight into the enzymatic mechanisms of activation, model in vitro studies were performed using [14C]diafenthiuron and microsomes from various vertebrate livers and from locust Malpighian tubules. Though there was a common set of metabolites, their quantities varies significantly with the species and assay conditions. As a typical product, p-hydroxydiafenthiuron was identified in assay with rat and mouse microsomes. The sulfomonoxide predominated in hen and fish assays, whereas pig and bovine microsomes almost exclusively produced the carbodiimide. The sulfoxide was shown to be a precursor of the carbodiimide. Formation of all metabolites was dependent on the presence of NADPH and active microsomes. The effects of inhibitors and the requirement for NAPDH suggested a role of cytochrome P450-dependent monooxygenase(s) in the formation of both the hydroxylated product and the carbodiimide. FAD-dependent monooxygenases (FMOs) may also be involved in a step following sulfoxidation. These in vitro studies revealed potential mechanisms contributing to biological selectivity of the effects of a pesticide that acts in a non-selective mode at a conserved mitochondrial site.
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PMID:Metabolism of diafenthiuron by microsomal oxidation: procide activation and inactivation as mechanisms contributing to selectivity. 1169 92

Selenium oxyanions, particularly selenite, can be highly toxic to living organisms. Few bacteria reduce both selenate and selenite into the less toxic elemental selenium. Insights into the mechanisms of the transport and the reduction of selenium oxyanions in Escherichia coli were provided by a genetic analysis based on transposon mutagenesis. Ten mutants impaired in selenate reduction were analysed. Three of them were altered in genes encoding transport proteins including a porin, an inner-membrane protein and a sulfate carrier. Two mutants were altered in genes required for molybdopterin biosynthesis, strongly suggesting that the selenate reductase of E. coli is a molybdoenzyme. However, mutants deleted in various oxomolybdenum enzymes described so far in this species still reduced selenate. Finally, a mutant in the gene ygfK encoding a putative oxidoreductase was obtained. This gene is located upstream of ygfN and ygfM in the ygfKLMN putative operon. YgfN and YgfM code for a molybdopterin-containing enzyme and a polypeptide carrying a FAD domain, respectively. It is therefore proposed that the selenate reductase of E. coli is a structural complex including the proteins YgfK, YgfM and YgfN. In addition, all the various mutants were still able to reduce selenite into elemental selenium. This implies that the transport and reduction of this compound are clearly distinct from those of selenate.
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PMID:Involvement of a putative molybdenum enzyme in the reduction of selenate by Escherichia coli. 1248 Aug 90