Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent tobacco-specific carcinogen, has been demonstrated to induce lung tumors in animals and is suspected to be a human carcinogen. Cytochromes P450 are the major enzymes responsible for the activation of NNK in microsomes from the lung and liver of rat and mouse, as well as human liver. The present study investigated the enzymes responsible for the metabolic activation of NNK in human lung microsomes. In the presence of a NADPH-generating system, the formation of keto aldehyde and keto alcohol (alpha-hydroxylation products, measured together), keto acid, hydroxy acid, and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was observed in human lung microsomes. Carbon monoxide (90%) decreased the rate of NNK oxidation by 5-49%, depending on the human lung microsomal samples analyzed. Coumarin decreased the oxidation of NNK by 9-34%, and an antibody against human P450 2A6 decreased the metabolism of NNK by 8-37%, suggesting the involvement of P450 2A6 in NNK oxidation. alpha-Napthoflavone inhibited NNK oxidation by 6-26%, possibly due to the inhibition of P450 1A1. P450 1A1-expressed microsomes catalyzed the formation of keto aldehyde and keto alcohol, exhibiting Km values of 1400 microM and 371 microM, respectively. In the absence of NADPH, NNK metabolism resulted in the formation of keto acid, keto aldehyde, and keto alcohol, and the activities in different lung samples were decreased by indomethacin (100 microM; cyclooxygenase inhibitor) or nordihydroguaiaretic acid (100 microM; lipoxygenase inhibitor) by 0-27% or 30-66%, respectively. The addition of arachidonic acid (10-100 microM) increased the rate of the formation of keto aldehyde and keto alcohol approximately 2-fold but inhibited the formation of keto acid. Soybean lipoxygenase increased the rate of formation of keto aldehyde and keto alcohol in a concentration-dependent manner. The increased rate in NNK oxidation by arachidonic acid or lipoxygenase was inhibited completely by nordihydroguaiaretic acid. Catalase, thiourea, and conjugated linoleic acid decreased the rate of NNK oxidation by 47, 20, and 45%, respectively. tert-Butyl-hydroperoxide, cumene hydroperoxide, and hydrogen peroxide increased the rate of formation of keto aldehyde and keto alcohol by 210, 40, and 50%, respectively. The results suggest that P450 enzymes are only partially responsible for the activation of NNK in human lung microsomes, and P450 2A6 or a P450 2A6-related enzyme seems to be involved in the activation. Furthermore, lipoxygenase and lipid hydroxperoxides may play important roles in the oxidation of NNK in human lung microsomes.
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PMID:Activation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in human lung microsomes by cytochromes P450, lipoxygenase, and hydroperoxides. 758 36

Diaphorase was studied as a possible oxidoreductase participating in NO production from some vasorelaxants. In the presence of NADH or NADPH, diaphorase can convert selected NO donors, glycerol trinitrate (GTN) and formaldoxime (FAL) to nitrites and nitrates with NO as an intermediate. This activity of diaphorase was inhibited by diphenyleneiodonium (DPI) (inhibitor of some NADPH-dependent flavoprotein oxidoreductases), while it remained uninhibited by NG-nitro-L-arginine methyl ester (inhibitor of NO synthase) 7-Ethoxyresorufin (inhibitor of cytochrome P-450 1A1 and cytochrome P-450 NADPH-dependent reductase) inhibited the conversion of GTN only. Existence of NO as an intermediate of the reaction was supported by results of electron paramagnetic resonance spectroscopy. In addition to its ability to affect the above mentioned NO donors, diaphorase was able to reduce 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO) and thus to eliminate its NO scavenging effect. This activity of diaphorase could also be inhibited by DPI. The reaction of diaphorase with GTN and PTIO was not affected by superoxide dismutase (SOD) or catalase. Reaction of FAL with diaphorase was lowered with SOD by 38 % indicating the partial participation of superoxide anion probably generated by the reaction of diaphorase with NADH or NADPH. Catalase had no effect. Diaphorase could apparently be one of the enzymes participating in the metabolism of studied NO donors to NO. The easy reduction and consequent elimination of PTIO by diaphorase could affect its use as an NO scavenger in biological tissues.
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PMID:Diaphorase can metabolize some vasorelaxants to NO and eliminate NO scavenging effect of 2-phenyl-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (PTIO). 1558 29