Citrulline synthesis regulation

The synthesis of NO requires merely one step the conversion of L-arginine into NO and citrulline. This conversion is catalyzed by the nitric oxide synthase (NOS) enzyme. Three distinct isoforms of the NOS enzyme have been cloned Isoform I (nNOS chromosome 12) is a Ca -dependent neuronal form of the enzyme Isoform n (mNOS or iNOS chromosome 17) is a Ca +-independent macrophage inducible form of the enzyme found in microglia Isoform III (eNOS, chromosome 7) is a Ca +-dependent form found in the endothelial cells that line blood vessels. Since NO is an extremely important messenger substance, the NOS enzyme is exquisitely regulated by processes such as phosphorylation and hormonal control. 

G. Wu and C. J. Meininger, Regulation of L-arginine synthesis from L-citrulline by L-glutamine in endothelial cells. Am J Physiol 265, H1965-H1971 (1993). 

The enzymes of the urea cycle, however, are not only expressed in the liver, but also in other tissues and cell types. In fact, it is believed that the urea cycle evolved from the arginine metabolic pathway present in lower organisms (Takiguchi et al, 1989). This difference in function between urea and arginine synthesis is reflected by the different tissue localization, function and regulation of the enzymes of the urea cycle and other enzymes involved in the metabolism of the urea cycle intermediates, arginine, citrulline and ornithine. 

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