The enzyme responsible for the biosynthesis of NO is the heme-containing protein, NOS (Fig. 17.1). The substrate for this enzyme, L-arginine, can be obtained from the diet or from intracel-lular protein degradation or endogenous synthesis involving the urea cycle. Molecular oxygen is also required by NOS to produce NO, as are calmodulin and four important cofactors: protonated nicotine adenine dinucleotide phosphate (NADPH), tetrahydrobiopterin (BH4), flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). Molecular oxygen is incorporated into the two products of this reaction - NO and L-citrulline. Further work has shown that the molecular chaperone heat shock protein 90 (HSP90) can modulate the activity of NOS in peripheral endothelial cells, where it is rapidly recruited to the NOS complex
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