l-Arginine-Incorporated Albumin Mesospheres: A Drug Delivery System for Cancer Therapy

Abstract

Arginine (2-amino-5-guanidinopentanoic acid), the cationic amino acid that carries most nitrogen atoms per molecule in humans, is the most common amino acids among the 20 amino acids that can be found naturally in vegetables and mammals. Arginine is considered as a semi-essential or conditionally essential amino acid because although it can be synthesized in humans, endogenous arginine biosynthesis is insufficient to compensate for depletion when cells are under stress or in different development stages (Appleton. Altern Med Rev 7:512–522, 2002). It has been identified as a precursor for initiation of various metabolic pathways in human body. The arginine through diet has to be uptaken by intestinal epithelial cells and transported through the cell membrane via the cationic amino acid transporters (CAT) (Closs et al. J Nutr 134:2752S–2759S, 2004). Half of arginine ingested in human body can be efficiently absorbed and converted to ornithine by arginase in urea cycle, as shown in Fig. 41.1 (Castillo et al. Am J Physiol 268:E360–E367, 1995; Wheatley. Anticancer Drugs 15:825–833, 2004). Then the arginine-derived ornithine can be metabolized to glutamate and proline, enzymatically degraded into polyamines, or converted to citrulline by ornithine transcarbamyl transferase (OCT). Through endogenous biosynthesis, besides the recycling of citrulline that is derived from ornithine, most arginine is converted from the citrulline produced in glutamine metabolism and released into circulation. Argininosuccinate synthetase (ASS) and argininosuccinate lyase (ASL) are the cytosolic enzymes catalyzing the two-step sequential conversion of citrulline to arginine. The conversion takes place in kidneys.