The article by Michael A. Marletta provides an in-depth review of nitric oxide synthase (NOS), the enzyme responsible for the synthesis of nitric oxide (NO). NOS has been a subject of intense study due to its critical role in biological processes and its structural similarity to other enzymes. The review highlights several key aspects of NOS, including its homology to NADPH cytochrome P-450 reductase, the presence of a cytochrome P-450-type heme, and its ability to perform P-450 chemistry in NO formation. It also discusses the relationship between NOS and cytochrome P-450 isoenzymes, the role of Ca2+/calmodulin in constitutive NOS isoforms, and the unique properties of inducible NOS (iNOS). The mechanism of NOS catalysis, involving the initial hydroxylation of L-arginine to N6-hydroxy-L-arginine (NHA) and subsequent conversion to NO and citrulline, is explored. The review also examines the different isoforms of NOS, their functional differences, and the regulation of their activity by Ca2+/CaM. Finally, it addresses the potential for end product inhibition by NO and concludes with a discussion on the overall structure-function relationship of NOS.The article by Michael A. Marletta provides an in-depth review of nitric oxide synthase (NOS), the enzyme responsible for the synthesis of nitric oxide (NO). NOS has been a subject of intense study due to its critical role in biological processes and its structural similarity to other enzymes. The review highlights several key aspects of NOS, including its homology to NADPH cytochrome P-450 reductase, the presence of a cytochrome P-450-type heme, and its ability to perform P-450 chemistry in NO formation. It also discusses the relationship between NOS and cytochrome P-450 isoenzymes, the role of Ca2+/calmodulin in constitutive NOS isoforms, and the unique properties of inducible NOS (iNOS). The mechanism of NOS catalysis, involving the initial hydroxylation of L-arginine to N6-hydroxy-L-arginine (NHA) and subsequent conversion to NO and citrulline, is explored. The review also examines the different isoforms of NOS, their functional differences, and the regulation of their activity by Ca2+/CaM. Finally, it addresses the potential for end product inhibition by NO and concludes with a discussion on the overall structure-function relationship of NOS.