Hormone-sensitive lipase

Lipase, hormone-sensitive
Identifiers
Symbols	LIPE ; AOMS4; FPLD6; HSL; LHS
External IDs	OMIM: 151750 MGI: 96790 HomoloGene: 3912 ChEMBL: 3590 GeneCards: LIPE Gene
EC number	3.1.1.79
Gene ontology Molecular function • triglyceride lipase activity • protein binding • protein kinase binding • hormone-sensitive lipase activity Cellular component • lipid particle • cytosol • caveola Biological process • protein phosphorylation • cholesterol metabolic process • lipid catabolic process • triglyceride catabolic process • long-chain fatty acid catabolic process • small molecule metabolic process • diacylglycerol catabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	3991	16890
Ensembl	ENSG00000079435	ENSMUSG00000003123
UniProt	Q05469	P54310
RefSeq (mRNA)	NM_005357	NM_001039507
RefSeq (protein)	NP_005348	NP_001034596
Location (UCSC)	Chr 19: 42.4 – 42.43 Mb	Chr 7: 25.38 – 25.4 Mb
PubMed search	[1]	[2]

Hormone-sensitive lipase (HSL) N-terminus
Identifiers
Symbol	HSL_N
Pfam	PF06350
InterPro	IPR010468
Available protein structures: Pfam structures PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Hormone-sensitive lipase (EC 3.1.1.79, HSL) also previously known as cholesteryl ester hydrolase (CEH) is an enzyme that, in humans, is encoded by the LIPE gene.

HSL is an intracellular neutral lipase that is capable of hydrolyzing a variety of esters. The enzyme has a long and a short form. The long form is expressed in steroidogenic tissues such as testis, where it converts cholesteryl esters to free cholesterol for steroid hormone production. The short form is expressed in adipose tissue, among others, where it hydrolyzes stored triglycerides to free fatty acids.

Nomenclature

During fasting-state the increased free fatty acid secretion by adipocyte cells was attributed to adrenaline hormone. Hence the name "hormone-sensitive lipase". Other hormones like catecholamines and adrenocorticotropic hormone (ACTH) can also stimulate such responses. Such enzymatic action plays a key role in providing major source of energy for most cells.

Function

The main function of hormone-sensitive lipase is to mobilize the stored fats. Mobilization and Cellular Uptake of Stored Fats (with Animation) HSL functions to hydrolyze the first fatty acid from a triacylglycerol molecule, freeing a fatty acid and diglyceride. It is also known as triglyceride lipase, while the enzyme that cleaves the second fatty acid in the triglyceride is known as diglyceride lipase, and the third enzyme that cleaves the final fatty acid is called monoglyceride lipase. Only the initial enzyme is affected by hormones, hence its hormone-sensitive lipase name. The diglyceride and monoglyceride enzymes are tens to hundreds of times faster, hence HSL is the rate-limiting step in cleaving fatty acids from the triglyceride molecule.

HSL is activated when the body needs to mobilize energy stores, and so responds positively to catecholamines, ACTH. It is inhibited by insulin. Previously, glucagon was thought to activate HSL, however the removal of insulin's inhibitory effects ("cutting the brakes") is the source of activation. The lipolytic effect of glucagon in adipose tissue is minimal in humans.

Another important role is the release of cholesterol from cholesterol esters for use in the production of steroids.

Activation

It may be activated by two mechanisms.

• In the first, phosphorylated perilipin A causes it to move to the surface of the lipid droplet, where it may begin hydrolyzing the lipid droplet.

• Also, it may be activated by a cAMP-dependent protein kinase (PKA). This pathway is significantly less effective than the first, which is necessary for lipid mobilization in response to cyclic AMP, which itself is provided by the activation of G_s protein-coupled receptors that promote cAMP production. Examples include beta adrenergic stimulation of the glucagon receptor and ACTH stimulation of the ACTH receptor in the adrenal cortex.

External links

• Hormone-Sensitive Lipase at the US National Library of Medicine Medical Subject Headings (MeSH)