Hormone-sensitive lipase--new roles for an old enzyme.
Although described initially as an intracellular adipocyte-specific triacylglycerol lipase, it is now clear that HSL (hormone-sensitive lipase) is expressed in multiple tissues and plays a number of roles in lipid metabolism, including that of a neutral cholesteryl ester hydrolase. The major isoform is a single polypeptide with a molecular mass of approx. 84 kDa and which comprises three major domains: a catalytic domain, a regulatory domain encoding several phosphorylation sites and an N-terminal domain involved in protein-protein and protein-lipid interactions. The activity of HSL is regulated acutely by several mechanisms, including reversible phosphorylation by a number of different protein kinases, translocation to different sites within the cell and interaction with a number of proteins, some of which may serve to direct the inhibitory products of HSL away from the protein. It is also apparent from work with HSL null mice that more than one enzyme species may be classified as a hormone-sensitive lipase. The possible presence of HSL in macrophages remains controversial, and the role of the protein in pancreatic beta-cells has yet to be fully elucidated. Altered expression of HSL in different cell types may be associated with a number of pathological states, including obesity, atherosclerosis and Type II diabetes.
Yeaman
Stephen J
SJ
School of Cell and Molecular Biosciences, Medical School, University of Newcastle, Newcastle upon Tyne NE2 4HH, UK. s.j.yeaman@ncl.ac.uk
D017667:Adipocytes / Q000201:enzymology; D000818:Animals; D001161:Arteriosclerosis / Q000201:enzymology; D002352:Carrier Proteins; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000201:enzymology; D008066:Lipolysis; D008264:Macrophages / Q000201:enzymology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D032342:Muscle Cells / Q000201:enzymology; D009765:Obesity / Q000201:enzymology; D009928:Organ Specificity; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000172:deficiency / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D051381:Rats; D002787:Sterol Esterase / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D011494:Protein Kinases; D002787:Sterol Esterase