Variation of the glycosylation of human pancreatic bile-salt-dependent lipase.

International audienceGlycoproteins of human pancreatic juice were characterized by means of lectins after electrophoresis and electrotransfer to nitrocellulose membranes. For the detected glycoproteins, only a 100-kDa glycoprotein varied in the pancreatic juice from a normal patient (i.e. without any pancreatic disorder) compared to the pancreatic juice from a patient suffering from chronic pancreatitis. This protein, which is the only protein in human pancreatic juice which is O-glycosylated and N-glycosylated, was identified as the bile-salt-dependent lipase. Among the glycosylated proteins present in human pancreatic juice, only the glycosylation of bile-salt-dependent lipase differs between individuals. The enzyme was isolated either from normal or pathological human pancreatic juices. The purified variants have an identical molecular mass and amino-acid composition. As suspected from lectin affinity studies, the oligosaccharide composition differs between the variants. The structure of the N-linked oligosaccharides of the variant from the pancreatic juice of a normal donor correlated with complete processing and maturation of a complex-type N-glycan. Alteration of the maturation process can be detected for a bile-salt-dependent-lipase variant from a patient suffering with chronic pancreatitis, since the carbohydrate composition is compatible with the predominance of hybrid or high-mannose-type structures. The amount of sugar involved in O-glycosylation associated with the peanut agglutinin reactivity suggests the presence of 12-14 minimal Gal beta 1-->3GalNac-->T/S O-glycan structures which are sialylated and fucosylated. The amount of sugar involved in the O-linked oligosaccharide structure appears to be unchanged in the variants isolated from the pathological pancreatic juice

Association between a polymorphism in the carboxyl ester lipase gene and serum cholesterol profile

Carboxyl ester lipase (CEL) is involved in the hydrolysis and absorption of dietary lipids, but it is largely unknown to what extent CEL could be involved in determining the serum lipid levels. The C-terminal part of CEL consists of a unique structure with proline-rich O-glycosylated repeats of 11 amino-acid residues each. The common variant of the human CEL gene contains 16 proline-rich repeats, but there is a high degree of polymorphism in the repeated region. While the biological function of the polymorphic repeat region is unknown, it has been suggested that it may be important for protein stability and/or secretion of the enzyme. Given that the polymorphism in the repeated region may affect the functionality of the protein, this study aimed to investigate whether the number of repeated units is correlated to serum lipid phenotype. Comparison of CEL repeat genotype and serum lipid phenotype revealed an association between the number of repeats and serum cholesterol profile. Individuals carrying at least one allele with fewer than the common 16 repeats had significantly lower total and low-density lipoprotein (LDL) cholesterol levels compared to individuals carrying two common alleles. This gives support to the notion that CEL may be involved in determining the plasma lipid composition