The Metabolism of Plasma Glycoproteins

Considerable interest has been manifest in the biosynthesis of protein-carbohydrate complexes as a result of the demonstration of their wide distribution in mammalian organs and body fluids. In recent years, significant progress has been made toward the elucidation of the chemical structure of plasma glycoproteins (l-5) in which the cardinal role of N-acetylglucosamine and N-acetylneuraminic acid has been established (3). Extensive studies on the biosynthesis of normal plasma proteins, with the use of r4C-labeled amino acids, have shown that the major plasma proteins, other than immunoglobulins, are synthesized by the liver (6-9). Moreover, it has also been observed that the turnover rate of plasma glycoproteins is 3 to 5 times faster than that of albumin (10). More recently, the tissue responsible for the incorporation of the carbohydrate constituents of the normal plasma glycoproteins has received increased attention. Studies on the biosynthesis of the serum glycoproteins with glucose-r% in normal rabbits (11, 12) and in rats (13-15) with glucose-r4C or glucosamine-1-14C as precursor have indicated that the labeled carbohydrates are rapidly incorporated by the liver: and that the labeled glycoprotein is subsequently discharged into the serum. Investigations on the isolated, perfused rat liver have substantiated the hepatic synthesis of serum glycoproteins (16, 17). The biosynthesis of N-acetylneuraminic acid, which occupies the terminal position on the oligosaccharide chain (3), has also been the subject of numerous studies. The enzymes involved in the synthesis of N-acetylneuraminic acid from N-acetylmannosamine and phosphoenolpyruvic acid in mammalian organs have been extensively investigated (18-22). Isolation of an enzyme which can catalyze the conversion of UDP-N-acetyl-nglucosamine to N-acetyl-n-mannosamine provided evidence that the metabolism of N-acetylneuraminic acid may be closely related to that of glucosamine (23, 24). This observation has been substantiated by studies in viva and in vitro with uniformly labeled glucose-r4C and glucose-6-r% as precursors (25-27). Although the central role of n-glucose in the biosynthesis of monosaccharides has been well established (28), it proves to be an undesirable precursor for studies on the metabolism of serum glycoproteins because of its utilization in a large variety of alternate metabolic pathways (10, 25, 27). On the other hand, there is considerable evidence that o-glucosamine-l-14C is exclusively converted to UDP-N-acetylhexosamine prior to its binding