6533b7d3fe1ef96bd1261365

RESEARCH PRODUCT

Expression and Expressional Control of Nitric Oxide Synthases in Various Cell Types

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Publisher Summary Nitric oxide (NO) can produce posttranslational modifications of proteins (via ADP ribosylation) and is capable of destroying parasites and tumor cells by inhibiting iron-containing enzymes or directly interacting with the DNA of these cells. In view of this multitude of functions of NO, it is important to understand how cells accomplish and regulate their NO production. Three isozymes of NOS have been identified, and their protein, cDNA, and genomic DNA structures have been elucidated. In humans NOS I, II, and III are encoded by three different genes, located on chromosomes 12, 17, and 7 respectively. The cDNAs for these enzymes have been isolated. All NOS isozymes oxidize a guanidino nitrogen of L-arginine. Molecular oxygen and reduced NADPH participate in NOS catalysis as cosubstrates. The first reaction step seems to be the formation of NG-hydroxy-L-arginine. All three isoforms of NOS contain flavin-adenine dinucleotide, flavin mononucleotide, and heme iron as prosthetic groups, and require the cofactor 6(R)-5,6,7,8-tetrahydrobiopterin (BH4). This chapter focuses on the cell and tissue distributions of the different isoforms of NOS and factors controlling their expression.