A MOLECULAR VIEW OF LIPOPROTEIN LIPASE AND HEPATIC LIPASE STRUCTURE AND FUNCTION

Abstract

Lipolytic enzymes play a pivotal role in the metabolism of triglyceride-rich lipoproteins circulating in plasma. The primary structures of many lipases have now been elucidated by molecular cloning of their cDNAs. To gain further insights into the molecular biology of lipoprotein lipase (LPL) and hepatic lipase (HL), we have determined their genomic organization. Both enzymes are members of a lipase gene family. Based on information derived from the genomic structures it is now possible to directly assess the molecular basis of familial LPLdefiency, a rare disorder of lipid metabolism involving the massive accumulation of chylomicrons in the plasma. Employing gene amplification techniques with LPL exon-specific oligonucleotide primers and direct DNA sequence determination, we have characterized a kindred with classical familial LPL-deficiency. Loss of LPL enzymatic activity was found to be caused by an amino acid substitution close to the putative active site.