Human hepatic lipase. Cloned cDNA sequence, restriction fragment length polymorphisms, chromosomal localization, and evolutionary relationships with lipoprotein lipase and pancreatic lipase.

作者：Santanu Datta, C C Luo, Wen‐Hsiung Li, Peter vanTuinen, David H. Ledbetter, Myles Brown, S H Chen, S W Liu, Lawrence Chan · 发表于：Journal of Biological Chemistry · 年份：1988 · DOI：10.1016/s0021-9258(19)57271-4 · 被引用次数：182 · 研究领域：Lipid metabolism and disorders、Diabetes and associated disorders、Pancreatic function and diabetes

Human hepatic lipase is an important enzyme in high density lipoprotein (HDL) metabolism, being implicated in the conversion of HDL2 to HDL3. Three human hepatic lipase cDNA clones were identified in two lambda gt11 libraries from human liver. The cDNA-derived amino acid sequence predicts a protein of 476 amino acid residues, preceded by a 23-residue signal peptide. Four potential N-glycosylation sites are identified, two of which are conserved in rat hepatic lipase. On alignment with human, mouse, and bovine lipoprotein lipase, the same two sites were also conserved in lipoprotein lipase in all three species. Stringent conservation of the cysteine residues was also evident. Comparative analysis of amino acid sequences shows that hepatic lipase evolves at a rapid rate, 2.07 x 10(-9) substitutions/site/year, about four times that in lipoprotein lipase and half that in pancreatic lipase. Further, hepatic lipase and pancreatic lipase appear to be evolutionarily closer to each other than either of them is to lipoprotein lipase. Southern blot analysis revealed high frequency restriction fragment length polymorphisms of the hepatic lipase gene for the enzymes HindIII and MspI. these polymorphisms will be useful for haplotype and linkage analysis of the hepatic lipase gene. Using cloned human hepatic lipase cDNA as a hybridization probe, we performed Southern blot analysis of a panel of 13 human-rodent somatic cell hybrids. Concordance analysis of the various hybrid clones indicates...