Glutaminolysis in Animal Cells

Abstract

Glutamine is the most abundant amino acid in plasma and most tissues (Van Slyke et al., 1943). Because of both empirical reasoning and cellular requirements determined experimentally, it is the most abundant amino acid in most cell culture media (Ham and McKeehan, 1979). Although other amino acids have metabolic functions in addition to protein and peptide synthesis, glutamine is the most versatile (Krebs, 1980). It is the major source of urinary nitrogen and a key factor in acid—base balance in mammals. The carbon skeleton of glutamine is an important precursor of glucose in kidney cortex and thus contributes to renal gluconeogenesis (Krebs, 1963; Goodman et al., 1966). Glutamine is a vehicle for transporting nitrogen among tissues. Skeletal muscle is the principal site of glutamine production. Release of glutamine from muscle is nearly four times that that can be accounted for by direct protein breakdown (Blackshear et al., 1975; Pardridge and Casenello-Ertl, 1979; Garber, 1980). The principal site of net glutamine metabolism appears to be the gut (Windmueller and Spaeth, 1974; Hanson and Parsons, 1977) followed by the liver (Blackshear et al., 1975). Glutamine is a key metabolite for elimination of toxic ammonia in nerve tissue and may be an important precursor of glutamate and a-aminobutyrate, a synaptic transmitter (Waelsch, 1960; Takagaki et al.,1961). In addition to its specific roles in multiple tissues, glutamine is the primary amino group donor in synthesis of purines and pyrimidines, amino sugars, pyridine nucleotides, and asparagine in mammalian cells. The reader is referred to the following books and reviews for an in-depth picture of the role of glutamine (and glutamate) in mammals: Meister (1956, 1965), Lund et al. (1970), Prusiner and Stadtman (1973), Shepartz (1973), Meister (1978), Munro (1978), Mora and Palacios (1980), Kovacevic and McGivan (1983).