[Recent data on hepatic lipase gene. Structure and functions of this enzyme].
Hepatic lipase (HL) is almost exclusively synthesized in the liver. Its gene is located on chromosome 15 in man, on chromosome 9 in rat, and has 9 exons and 8 introns. Inhibitory and activator sequences have been found at the 5' end of the gene, upstream to the initiation site, as well as several consensus sequences such as TRE, SRE, AP-2, CEBP, ERE, AF1 and OCT-1. Glycosylation is an essential step for full active mature protein. The catalytic site is in the N-terminal part of the lipase gene while the lipid binding site is at its C-terminal end. HL is generally thought to be active as a dimer. This enzyme hydrolyses the acyl ester bonds of glycerides and phospholipids as well as the acyl CoA-thiol ester bonds. After being secreted by the hepatocytes, HL remains on the surface of hepatic endothelial cells and hepatocytes, bound to heparan sulfate proteoglycans, where it acts on the uptake of chylomicron remnants, IDL and HDL cholesterol ester. HL also participates in the VLDL to IDL and LDL cascade and in the conversion of HDL2 to HDL3 and pre-beta 1 HDL. Thus, HL plays an important role in lipoprotein metabolism and in reverse cholesterol transport and may thus be involved in atherogenic processes. Moreover, HL expression is regulated by hormones and nutritional state in the pre- and post-natal periods. Therefore, it appears of interest to gain further insight into the regulation of HL gene expression in order to better understand plasma lipoprotein metabolism.
Arca-Sedda Benhizia
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F
Unité Inserm U177, Paris, France.
Lagrange
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D
Griglio
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S
D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D005796:Genes; D006801:Humans; D008049:Lipase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008074:Lipoproteins / Q000378:metabolism; D008099:Liver / Q000201:enzymology*
D008074:Lipoproteins; D008049:Lipase