Molecular pathobiology of the human lipoprotein lipase gene

Lipoprotein lipase (LPL; E.C. 3.1.1.34) is a key enzyme in the metabolism of lipids. Many diseases, including obesity, coronary heart disease, chylomicronemia (pancreatitis), and atherosclerosis, appear to be directly or indirectly related to abnormalities in LPL function. Human LPL is a member of a...

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Bibliographic Details
Published in:Pharmacology & therapeutics (Oxford) 1996, Vol.70 (2), p.101-135
Main Authors: Murthy, Ven, Julien, Pierre, Gagné, Claude
Format: Article
Language:English
Subjects:
Amino Acid Sequence
chylomicronemia syndrome
Familial lipoprotein lipase deficiency
gene mutations
hepatic lipase
Humans
Hyperlipoproteinemia Type I - physiopathology
Lipase - genetics
Lipase - physiology
lipase gene family
Lipoprotein Lipase - classification
Lipoprotein Lipase - genetics
Molecular Sequence Data
pancreatic lipase
Point Mutation
Sequence Homology, Amino Acid
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Summary:Lipoprotein lipase (LPL; E.C. 3.1.1.34) is a key enzyme in the metabolism of lipids. Many diseases, including obesity, coronary heart disease, chylomicronemia (pancreatitis), and atherosclerosis, appear to be directly or indirectly related to abnormalities in LPL function. Human LPL is a member of a superfamily of lipases that includes hepatic lipase and pancreatic lipase. These lipases are characterized by extensive homology, both at the level of the gene and the mature protein, suggesting that they have a common evolutionary origin. A large number of natural mutations have been discovered in the human LPL gene, which are located at different sites in the gene and affect different functions of the mature protein. There is a high prevalence of two of these mutations (207 and 188) in the Province of Québec, and one of them (207) is almost exclusive to the French-Canadian population. A study of these and other naturally occurring mutant LPL molecules, as well as those created in vitro by site-directed mutagenesis, indicate that the sequence of LPL is organized into multiple structural and functional units that act in concert in the normal enzyme. In this review, we discuss the interrelationships of LPL structure and its function, the molecular etiology of abnormal LPL in humans, and the clinical and therapeutic aspects of LPL deficiency.
ISSN:0163-7258
1879-016X
DOI:10.1016/0163-7258(96)00005-8