Kinetic characteristics of nitric oxide synthase from rat brain.
The relationship between the rate of synthesis of nitric oxide (NO) and guanylate cyclase stimulation was used to characterize the kinetics of the NO synthase from rat forebrain and of some inhibitors of this enzyme. The NO synthase had an absolute requirement for L-arginine and NADPH and did not require any other cofactors. The enzyme had a Vmax. of 42 pmol of NO formed.min-1.mg of protein-1 and a Km for L-arginine of 8.4 microM. Three analogues of L-arginine, namely NG-monomethyl-L-arginine, NG-nitro-L-arginine and NG-iminoethyl-L-ornithine inhibited the brain NO synthase. All three compounds were competitive inhibitors of the enzyme with Ki values of 0.7, 0.4 and 1.2 microM respectively.
Wellcome Research Laboratories, Beckenham, Kent, U.K.
R G
RG
Knowles
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M
Palacios
R M
RM
Palmer
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S
Moncada
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001667:Binding, Competitive; D001921:Brain / Q000201:enzymology*; D004027:Diencephalon / Q000201:enzymology; D006162:Guanylate Cyclase / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009249:NADP / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009952:Ornithine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D013574:Synaptosomes / Q000201:enzymology; D013687:Telencephalon / Q000201:enzymology; D014018:Tissue Distribution; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; C065027:N(G)-iminoethylornithine; D009249:NADP; D001120:Arginine; D009952:Ornithine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D006162:Guanylate Cyclase