Modification of the intramolecular turnover of terminal carbohydrates of dipeptidylaminopeptidase IV isolated from rat‐liver plasma membrane during liver regeneration

Abstract

An intramolecular turnover of the terminal carbohydrates L-fucose, N-acetylneuraminic acid and D-galaCtOSe is a characteristic property of several liver plasma membrane glycoproteins, first demonstrated for dipeptidylaminopeptidase IV (EC 3.4.14.5., DPP IV). The core carbohydrates D-mannOSe and N-acetyl-D-glucosamine turn over like the polypeptide chain. The ratio of apparent half-lives of L-fucose and L-methionine of DPP IV is shifted from 0.17 in normal liver to 0.60 in regenerating liver. The ratio of half-lives of N-acetylneuraminic acid and L-methionine is only slightly changed from 0.43 in normal liver to 0.61 in regenerating liver. The ratio of apparent half-lives of D-mannose and L-methionine amounts to 0.80 in normal liver and 0.71 after partial hepatectomy. From this a drastic reduction of the intramolecular turnover of L-fucose on plasma membrane DPP IV in regenerating liver can be derived. The intramolecular N-acetylneuraminic acid turnover is affected to only a minor extent. D-Mannose turns over like the polypeptide in both normal and regenerating liver. The intramolecular L-fucose turnover may be involved in membrane glycoprotein recycling, which presumably is altered in regenerating liver. Additionally, L-fucose could regulate the rate of degradation of DPP IV, since core-fucosylated glycoproteins appear to be resistant to mammalian endo-N-acetylglucosaminidase.The glycoproteins of the hepatocyte plasma membrane are involved in a variety of functions such as enzymatic activity, antigenicity, receptor and transport function and cellular communication [l 1. Their actual concentration in the membrane depends on de novo synthesis, insertion into and removal from the membrane, including an eventual recycling, and degradation. Each of these processes is influenced by numerous endogenous and exogenous factors [2]. In contrast to other cell systems [3], the glycoproteins of liver and hepatoma plasma membrane are not turned over in bulk, but exhibit a marked intermolecular heterogeneity with respect to their individual turnover rates and half-lives [4 -1 I]. In previous publications we described an intramolecular heterogeneity in the turnover of dipeptidylaminopeptidase IV (DPP 1V) isolated from rat liver plasma membrane. The terminal carbohydrates L-fucose, N-acetylneuraminic acid and D-galactose possess half-lives much shorter than the polypeptide moiety. That is, terminal carbohydrates turn over several times during the life span of this glycoprotein [12,13]. The core carbohydrates D-mannose and N-acetyl-D-glucosamine behave similarly to the polypeptide [14]. Recently this effect was demonstrated for other plasma membrane glycoproteins of rat liver [15] and a hepatoma cell line [16].Rapid growth after partial hepatectomy is a condition with characteristic alterations of glycoprotein metabolism. This controlled liver cell proliferation causes a drastic inhibition of the degradation of cellular proteins [17] including plasma membrane proteins and glycoproteins [9,18,19]. Turnover studies of the different ...

Rapid intramolecular turnover of N‐linked glycans in plasma membrane glycoproteins

“…In contrast to hepatoma, intramolecular turnover in plasma membrane glycoproteins of liver is restricted to the terminal and penultimate sugars of the glycoprotein glycans, whereas the core sugar Dmannose is slowly degraded at the same rate as the protein [4 -61. In rapidly proliferating liver after partial hepatectomy, as opposed to both normal liver and hepatoma, L-fucose turns over significantly more slowly with a half-life adjusted to the half-lives of D-mannose and the polypeptide [34]. Hence, according to the present data, the intramolecular turnover of the different sugar residues of plasma membrane glycoproteins is modulated in response to growth and malignant transformation.…”

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