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[Effect of a protein-deficient diet (5 p. 100 gluten) and of balanced refeeding (15 p. 100 casein) on potential lipase, colipase-dependent lipase and phospholipase A2 activities. I. In the growing rat pancreas].

The intake of a 5 p. 100 gluten diet as the only protein source caused an overall protein synthesis deficiency that immediately stopped the rat growth. At first, the pancreas was less affected than the rest of the organism, but after 29 days of malnutrition, there was a 40 p. 100 decrease in body and pancreatic weight. The protein level of the deficient pancreas remained at that of the controls. Refeeding caused a considerable but temporary increase in that level after 24 h. The specific enzyme activities (AS) showed high variations from one day to the other, but only phospholipase A2 AS was significantly affected by the deficiency (--50 p. 100). Total lipase activities of the pancreas were reduced by 50 p. 100 and those of phospholipase A2 by 70 p. 100. Refeeding caused a considerable increase in lipase activities in 12 h and in phospholipase A2 activity in 48 h, but this process was brief and did not indicate complete recovery of those activities. After 27 days of refeeding, only phospholipase A2 showed good levels. Adding methionine to the deficient diet only changed the colipase level; this constitutes one more argument in favor of a distinct synthesis for this factor and for lipase.

Animals↗

Specific serum pancreatic lipase determination, with use of purified colipase.

We show that the turbidimetric method of Ziegenhorn et al. (Clin. Chem. 25: 1067, 1979) for determination of pancreatic lipase is not influenced by lipoprotein lipase. This improved specificity as compared to standard lipase methods is explained by the presence of purified colipase and the high concentration of bile acids in the substrate emulsion.

Bile Acids and Salts↗

Pancreatic lipase and colipase: an example of heterogeneous biocatalysis.

The hydrolytic reactions catalyzed by pancreatic lipase represent a good example of heterogeneous catalysis. The particularity of this enzyme is provided by its preferential action on emulsified substrates. The first step of catalysis resides in a reversible adsorption of the enzyme to the oil-water interface. In fact, the formation of this adsorption complex is an obligatory step for the enzyme to display its full activity. Two principal but not necessarily exclusive hypotheses have been proposed to explain the observed interfacial activation: Either the interface confers new properties on the substrate which allow its subsequent hydrolysis, or the enzyme itself is modified by adsorption at the interface. Different approaches have recently been developed to clarify this point further. The results obtained by chemical modifications of lipase are consistent with the following hypothesis. The active site preexists in solution and becomes fully functional only by interaction of the interface with an additional site on the enzyme molecule which can be tentatively called the "interfacial activation site." Finally, a protein of low molecular weight, colipase, seems necessary for lipase to express its activity under physiological conditions. This protein enters specific interactions with bile salts micelles and is responsible for the reversal of the inhibition of lipolysis brought about by these detergents.

Animals↗

Chromosomal localization of lipolytic enzymes in the mouse: pancreatic lipase, colipase, hormone-sensitive lipase, hepatic lipase, and carboxyl ester lipase.

Several lipases and their cofactors are involved in the absorption, transport, storage, and mobilization of lipids. As part of an effort to examine the role of these enzymes in plasma lipid metabolism and genetic susceptibility to atherosclerosis, we report the chromosomal mapping of their genes in mouse. Restriction fragment length variants for each gene were identified, typed in an interspecific cross, and tested for linkage to known chromosomal markers. The gene for pancreatic lipase resides on chromosome 19, while the gene for its cofactor, colipase, is on chromosome 17. A gene for a protein with sequence similarity to pancreatic lipase was tightly linked (no observed recombination) to the gene for pancreatic lipase, suggesting a gene cluster. The gene for hormone-sensitive lipase is near the gene cluster containing apolipoproteins C-II and E on chromosome 7. The gene for hepatic lipase is near the gene for apolipoprotein A-I on chromosome 9. The carboxyl ester lipase gene resides on chromosome 2. Previously, we have mapped the gene for lipoprotein lipase to chromosome 8. Thus, with the exception of pancreatic lipase and a related protein, these lipase genes, including several that are members of a gene family, are widely dispersed in the genome. Comparison of chromosomal locations for these genes in mouse and humans shows that the previously observed interspecies syntenies are preserved.

Animals↗