Biochemical and molecular characterization of mitochondrial membrane bound arginase in fish and mice liver

Abstract

The arginase [E.C. 3.5.3.1], that catalyses hydrolysis of arginine into ornithine and urea has been critical from microorganisms to mammals for homeostasis of arginine and synthesis of glutamate, glutamine, proline and polyamines. It has also been considered important biomarker in several pathological conditions like diabetes, immune response, vascular diseases, cardiovascular diseases, neurological complications, carcinoma, and endothelial dysfunction. The arginase expressed in mitochondria and involved in generation of ornithine, glutamate and proline has been explained as arginase-II. However, arginase which is predominant in cytosol and important for removal of nitrogenous waste in the form of urea has been known as arginase-I. Based on KCl-dependent increase in the activity of arginase in mitochondrial and cytosolic fractions of liver, mitochondrial membrane-bound arginase has also been proposed from rat (Rattus norvegicus) and a catfish (Heteropneustes fossilis). It has been hypothesized that mitochondrial membrane-bound may be cytosolic arginase-I adsorbed at the surface of sub-cellular organelles. However, no biochemical, molecular or cytological evidences are lacking. It is presumed that 150 mM KCl may not only induce release of arginase bound with membrane of mitochondria but may also affect integrity of mitochondria and other cell organelles. It is likely that arginase-II gets released from mitochondria due to alterations in permeability or damage of mitochondrial membrane under non-optimal KCl concentration during isolation procedure. Therefore, mitochondrial membrane-bound arginase could either be a novel product of transcript variant or a form of arginase-II or arginase-I which got phosphorylated, acetylated or glycosylated and evolved for better channeling of substrate from cytoplasm and mitochondria or to enhance the rate of the reaction of arginine in both cytosolic and mitochondrial compartment. newline