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Oxygen: The Overlooked Substrate for Nitric Oxide Synthases
Author(s) -
Gao Yingtong,
Panda Satya Prakash,
Roman Linda J,
Martasek Pavel,
Ishimura Yuzuru,
Masters Bettie Sue
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a622-d
Subject(s) - tetrahydrobiopterin , nitric oxide , endothelial nos , chemistry , gene isoform , arginine , biochemistry , cofactor , substrate (aquarium) , nos1 , nitric oxide synthase , biopterin , enos , oxygenase , reactive oxygen species , calmodulin , enzyme , biology , amino acid , ecology , organic chemistry , gene
Nitric oxide synthases (NOS) are novel oxygenases that catalyze the formation of nitric oxide (NO) from L‐arginine. A variety of factors, including the presence of Ca 2+ /calmodulin/L‐arginine/N G ‐hydroxy‐L‐arginine/and/or tetrahydrobiopterin (BH 4 ), determine the products of O 2 reduction and incorporation. In spite of intensive research in the NOS/NO field, O 2 metabolism by NOS has been incompletely defined. Recent studies from this laboratory now demonstrate that the three NOS isoforms respond differentially to various substrates, inhibitors and cofactors with respect to O 2 uptake and product formation. The stoichiometry of NADPH oxidized vs . O 2 metabolized can be exactly as predicted theoretically in the absence of substrate or cofactors, i.e ., in the un coupled state for both neuronal and endothelial NOS isoforms. However, the influence of L‐arginine and tetrahydrobiopterin is quite distinct for these isoforms, with O 2 uptake being stimulated in nNOS and inhibited in eNOS by L‐arginine addition. The percentage of coupling of O 2 uptake to NADPH oxidation is differentially affected in the three isoforms and modulation of these activities profoundly affects the formation of oxygenated products. These results have physiological implications on the roles of NOS isoforms in the production of reactive O 2 species and nitrogen oxides in various tissues. (Supported by NIH GM52419 to BSSM)