Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Selenium deficiency has been reported to result in an extraordinary decrease of glutathione peroxidase (GSH-Px) and, reversely, an increase of detoxifying enzymes such as glutathione-S-transferase (GST), uridine-5'-diphosphate glucuronosyltransferase (UGT), nicotinamide-dependent quinine oxidoreductase (NQO1; DT-diaphorase), and epoxide hydrolase without significantly affecting cytochrome P450 activity. However, little is known about the effects on aldehyde oxidase 1 (AOX1) activity towards various kinds of aldehydes and N-heterocyclic aromatic compounds. The aim of this study is to clarify the effects of selenium deficiency on AOX1 in rats. As expected, selenium deficiency was confirmed by the extremely low activity of GSH-Px along with the increased activities of GST and DT-diaphorase. AOX1 activity towards vanillin and (S)-RS-8359 was increased by selenium deficiency, and that corresponded to an increase of AOX1 protein level but not to a decreased AOX1 mRNA level. It has been documented that the assembly of the catalytically active holoenzyme forms of the molybdo-flavoenzyme family is very complex and is controlled through transcriptional and translational events by many gene products. In addition, selenium deficiency has been known to cause oxidative stress that leads to an increase of AOX1 activity. Furthermore, aldehyde oxidase homolog 1 (AOH1) with properties similar to AOX1 is present in rodent liver. All the reports suggest that the mechanisms by which selenium deficiency increases AOX1 activity are highly complicated and investigated from different points of view.
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PMID:Effects of selenium deficiency on aldehyde oxidase 1 in rats. 1918 74

Oxycodone is used as a potent analgesic medication. Oxycodone is extensively metabolized. To fully describe its metabolism, the oxygenation of oxycodone to oxycodone N-oxide was investigated in hepatic preparations. The hypothesis tested was that oxycodone N-oxygenation was enzymatic and the amount of N-oxide detected was a consequence of both oxygenation and retro-reduction. Methods for testing the hypothesis included both in vitro and in vivo studies. Results indicated that oxycodone was N-oxygenated by the flavin-containing monooxygenase. Oxycodone N-oxide is chemically quite stable but in the presence of hepatic preparations and NADPH was retro-reduced to its parent compound oxycodone. Subsequently, oxycodone was metabolized to other metabolites including noroxycodone, noroxymorphone, and oxymorphone via cytochrome P-450. Retro-reduction of oxycodone N-oxide to oxycodone was facilitated by quinone reductase, aldehyde oxidase, and hemoglobin but not to a great extent by cytochrome P-450 or the flavin-containing monooxygenase. To confirm the in vitro observations, oxycodone was administered to rats and humans. In good agreement with in vitro results, substantial oxycodone N-oxide was observed in urine after oxycodone administration to rats and humans. Administration of oxycodone N-oxide to rats showed substantial amount of recovered oxycodone N-oxide. In vivo, noroxycodone was formed as a major rat urinary metabolite from oxycodone N-oxide presumably after retro-reduction to oxycodone and oxidative N-demethylation. To a lesser extent, oxycodone, noroxymorphone, and oxymorphone were observed as urinary metabolites. SIGNIFICANCE STATEMENT: This manuscript describes the N-oxygenation of oxycodone in vitro as well as in small animals and humans. A new metabolite was quantified as oxycodone N-oxide. Oxycodone N-oxide undergoes extensive retro-reduction to oxycodone. This re-establishes the metabolic profile of oxycodone and introduces new concepts about a metabolic futile cycle related to oxycodone metabolism.
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PMID:N-Oxygenation of Oxycodone and Retro-reduction of Oxycodone N-Oxide. 3172 73


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