Arginine/Arginase NO NO NO

Abstract

Arginine is a semi-essential amino acid that plays a critical role in several metabolic pathways. The best known of these is as the immediate precursor of urea in the liver and to a lesser extent in the intestine.1 The enzyme responsible for the cleavage of arginine to produce urea is arginase, which is the only enzyme in the urea cycle that comes in two forms, arginase I, a cytosolic enzyme, and arginase II, a mitochondrial enzyme. These enzymes exist not only in the liver and intestine where urea is generated but are also widely distributed in the body. Ornithine, the other product of the cleavage of arginine by arginase, is a precursor of proline and polyamines such as spermine, spermidine, and putrescine. Arginine is also the precursor of nitric oxide (NO). See page 365 In an important article authored by Teupser and colleagues,2 arginase in macrophages has been identified as a candidate gene influencing atheroresponsiveness. They created and studied two strains of rabbits with genetically determined high (HAR) and low (LAR) atherosclerosis susceptibility. Subtractive suppression hybridization was used to screen for genes that were more highly expressed in macrophages from LAR rabbits. Among the 42 clones identified were four differentially expressed genes with potential relevance to atherogenesis. These were OC2 protein, fibronectin, ferritin H-chain, and arginase I. Despite their identification in the screen, the first three genes were not differentially expressed in macrophages between HAR and LAR animals when checked by quantitative RT-PCR. In contrast, arginase I was more highly expressed in LAR than HAR macrophages, and its expression level was correlated with higher arginase enzymatic activity. They further identified a length polymorphism of the mRNA for arginase I that was attributable to the presence (long variant) or absence (short variant) of a 413-bp C repeat in the …