Fig. 4.

l-Arginine (l-Arg) pools in the context of the metabolic network of l-arginine in cytosol and mitochondria, including NO synthesis and arginase activity. The concept of specific subcellular l-arginine pools is complex and is dependent not only on the knowledge of the specific membrane cationic transporters but also on an understanding of the networks for l-arginine metabolism in both the cytoplasmic and mitochondrial compartments as well as its coupling to urea synthesis. The picture that seems to be emerging is summarized in the above figure. Pool I is freely exchangeable with extracellular l-arginine and is regulated by the cationic transporter (CAT). This pool can be depleted by exchanging the pool with the cationic amino acid lysine. Pool II, on the other hand, is not exchangeable with extracellular l-arginine and cannot be depleted by extracellular lysine. Part of pool II, pool IIA, appears to be a function of the recycling of citrulline to arginine with arginosuccinate synthetase (ASS) and arginosuccinate lyase (ASL) being critical enzymes. Ornithine is converted to citrulline by ornithine transcarbamylase (OTC). Finally, the remaining component of pool II, pool IIB (not shown) cannot be depleted by the neutral amino acids such as histidine (perhaps by transtimulation/exchange and depletion of recycling citrulline) through the system N, neutral amino acid (NAA), transporter (SN1) and is likely provided by protein breakdown. ORTN1, ornithine/citrulline exchanger (transporter); CYT, cytoplasm; MIT, mitochondria.