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)

Liver and kidney of the teleost cod, Gadus morhua, contained oxygen- and NADPH-dependent monooxygenase which mediated the oxidation of trimethylamine (TMA) to trimethylamine oxide (TMAO). The microsomal monooxygenase of liver was partially characterized. The rate of enzymic TMA oxidation had its maximum at pH 8.2 and at 24 degrees C. The enzyme displayed Michaelis-Menten kinetics; the apparent Km value for TMA being 11 microM. All N,N-dimethyl-n-alkylamines with up to 8 carbons in the side chain were oxidized at almost the same rate. The oxidation of TMA was stimulated by octylamine and tyramine, and its ws inhibited by the --SH reagents N-ethylmaleimide and p-chloromercurybenzoate. Lack of inhibition by carbon monoxide and stimulation by FAD indicated that the enzyme was a cytochrome P-450-independent flavoprotein. [14C]TMA injected intraperitoneally into cod was oxidized to [14C]TMAO. After its compartmentation the [14C]TMAO produced was excreted at a rate of approximately 0.5%/day in cod fed a TMAO-rich diet. It was inferred that high stability of body TMAO and a surplus amount of TMAO in their natural diet can explain the lack of endogenous TMAO synthesis encountered in many TMAO-containing marine fish.
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PMID:Biosynthesis and turnover of trimethylamine oxide in the teleost cod, Gadus morhua. 726 38

The metabolism and action of chlorpropham (isopropyl N-(3-chlorophenyl)carbamate; CIPC, a post-harvest agent) and its metabolites were studied in freshly isolated rat hepatocytes and isolated rat hepatic mitochondria, respectively. The exposure of hepatocytes to CIPC caused a concentration (0.25-1.0 mM)- and time (0-3h)-dependent cell death accompanied by loss of cellular ATP and adenine nucleotides. CIPC at a weakly toxic level (0.5 mM) was metabolized to isopropyl N-(3-chloro-4-hydroxyphenyl)carbamate (4OH-CIPC) and subsequently to its glucuronide and sulfate conjugates (major metabolites) or alternatively to a minor metabolite 3-chloroaniline (3CA). The addition of SKF-525A (50 microM), an inhibitor of microsomal monooxygenase, enhanced the CIPC (0.5 mM)-induced cytotoxicity accompanied by loss of ATP and 4OH-CIPC and inhibited the decrease in the concentration of the parent compound. CIPC led to a strong decrease in cellular ATP content compared to its metabolites, 4OH-CIPC and 3CA. On the other hand, the exposure of isolated hepatic mitochondria to CIPC reduced State 3 respiration with a FAD-linked substrate (succinate plus rotenone) and/or with a NAD+ -linked substrate (pyruvate plus malate), whereas State 3 respiration with ascorbate plus tetramethyl-p-phenylendiamine (cytochrome oxidase-linked respiration) was not affected markedly by CIPC. Further, the addition of CIPC caused an increase in the rate of State 4 oxygen consumption, indicating an uncoupling effect, and a decrease in the rate of State 3 oxygen consumption in a concentration-dependent manner, respectively. In contrast, the addition of neither 4OH-CIPC nor 3CA markedly affected the rate of states 3 and/or 4 oxygen consumption. These results indicate that CIPC-induced cytotoxicity is mediated by the parent compound rather than by its metabolites such as 4OH-CIPC and 3CA, and that the toxicity is associated with a rapid depletion of ATP via impairment of mitochondrial function related to oxidative phosphorylation.
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PMID:Chlorpropham induces mitochondrial dysfunction in rat hepatocytes. 1521 9