Definition

A genetically modified form of human enzyme arginase (ARG) site-specifically linked with a linear 20 kDa polyethylene glycol (PEG), with potential arginine depleting and antineoplastic activities. Upon intravenous administration of pegtomarginase, arginase metabolizes the amino acid arginine to ornithine and urea, thereby lowering blood arginine levels. This normalizes blood arginine levels in patients with arginase deficiency and prevents hyperargininemia. As many cancer types lack the ability to synthesize arginine due to deficient expression of certain metabolic enzymes of the urea cycle and are dependent on extracellular arginine uptake for their proliferation, depriving cancer cells of arginine inhibits their proliferation. In normal, healthy cells, arginine is synthesized intracellularly by metabolic enzymes of the urea cycle, including ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS), and argininosuccinate lyase (ASL), and they are not dependent on extracellular arginine for survival. Pegylation improves blood circulation times of this agent.