Hormone-sensitive lipase

LIPE
Identifiers
Aliases	LIPE, AOMS4, FPLD6, HSL, LHS, lipase E, hormone sensitive type, REH
External IDs	OMIM: 151750; MGI: 96790; HomoloGene: 3912; GeneCards: LIPE; OMA:LIPE - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19q13.2 Start 42,401,514 bp[1] End 42,427,388 bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7 A3|7 13.78 cM Start 25,078,952 bp[2] End 25,098,135 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in subcutaneous adipose tissue pericardium inferior ganglion of vagus nerve middle frontal gyrus inferior olivary nucleus subthalamic nucleus substantia nigra corpus callosum left ventricle pons Top expressed in brown adipose tissue white adipose tissue subcutaneous adipose tissue seminiferous tubule intercostal muscle ankle joint adrenal gland ankle spermatid lip More reference expression data BioGPS More reference expression data
Gene ontology Molecular function lipase activity triglyceride lipase activity hormone-sensitive lipase activity protein binding hydrolase activity protein kinase binding serine hydrolase activity Cellular component cytoplasm membrane lipid droplet plasma membrane caveola cytosol Biological process diacylglycerol catabolic process steroid metabolic process lipid metabolism cholesterol metabolic process lipid catabolic process protein phosphorylation long-chain fatty acid catabolic process metabolism triglyceride catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3991 16890 Ensembl ENSG00000079435 ENSMUSG00000003123 UniProt Q05469 P54310 RefSeq (mRNA) NM_005357 NM_001039507 NM_010719 RefSeq (protein) NP_005348 NP_001034596 NP_034849 Location (UCSC) Chr 19: 42.4 – 42.43 Mb Chr 7: 25.08 – 25.1 Mb PubMed search [3] [4]
Wikidata
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Hormone-sensitive lipase (EC 3.1.1.79, HSL), also previously known as cholesteryl ester hydrolase (CEH),^[5] sometimes referred to as triacylglycerol lipase, is an enzyme that, in humans, is encoded by the LIPE gene,^[6] and catalyzes the following reaction:

(1) diacylglycerol + H₂O = monoacylglycerol + a carboxylate

(2) triacylglycerol + H₂O = diacylglycerol + a carboxylate

(3) monoacylglycerol + -H₂O = glycerol + a carboxylate

HSL is an intracellular neutral lipase capable of hydrolyzing a variety of esters.^[7] 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.^[8]

Nomenclature

During fasting-state the increased free fatty acid secretion by adipocyte cells was attributed to the hormone epinephrine, hence the name "hormone-sensitive lipase".^[9] Other 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.

Activation

Extracellular hormones, such as glucagon, epinephrine, thyroid-stimulating hormone, or adrenocorticotropic hormone (ACTH), bind to their respective G protein–coupled receptors (GPCR). When a GPCR is activated by its extracellular ligand, a conformational change is induced in the receptor that is transmitted to an attached intracellular heterotrimeric G protein complex by protein domain dynamics. The Gs alpha subunit of the stimulated G protein complex exchanges GDP for GTP in a reaction catalyzed by the GPCR and is released from the complex. The activated Gs alpha subunit binds to and activates an enzyme called adenylyl cyclase, which, in turn, catalyzes the conversion of ATP into cyclic AMP (cAMP). cAMP binds to and activates protein kinase A (PKA). It is PKA, activated by a hormone-induced signal transduction cascade, that phosphorylates and activates hormone sensitive lipase (HSL), hence the name. In addition to phosphorylating HSL, PKA phosphorylates perilipins on the surface of lipid droplets within adipose cells. This triggers them to "spread out" and allow for HSL to enter the lipid droplet. ^[10]

Activation of partially purified HSL requires Mg²⁺, ATP, and cyclic AMP.^[11] Activation can be blocked when Ser552 is not phosphorylated because Ser554 is phosphorylated and when the dephosphorylation of Ser552 causes insulin to the insulin receptor, causing inhibition of lipolysis and stimulation of glucose transport.^[12]

Hormone stimulation of lipolysis in humans is similar to rats.^[11]

Function

The main function of hormone-sensitive lipase is to mobilize stored fats.^[13] HSL functions to hydrolyze either a fatty acid from a triacylglycerol molecule, freeing a fatty acid and diglyceride, or a fatty acid from a diacylglycerol molecule, freeing a fatty acid and monoglyceride. This process allows energy metabolism in mammals.^[12] Although HSL is able to catalyze hydrolysis of triglycerides and diglycerides, another enzyme found in adipose tissue, adipose triglyceride lipase (ATGL), has a higher affinity for triglycerides than HSL, and ATGL predominantly acts as the enzyme for triglyceride-specific hydrolysis in the adipocyte. Hormone-sensitive lipase, which has 11-fold greater affinity for diglycerides than triglycerides, predominantly cleaves these diglycerides, forming 2-monoglyceride and a free fatty acid.^[14][15]

HSL is activated when the body needs to mobilize energy stores, and so responds positively to catecholamines and ACTH. It is inhibited by insulin.^{[citation needed]}

Another important role is the release of cholesterol from cholesteryl esters for use in the production of steroids^[16] and cholesterol efflux.^[17] Activity of HSL is important in preventing or ameliorating the generation of foam cells in atherosclerosis.^[17]

References

Further reading

External links

• Hormone-Sensitive+Lipase at the U.S. National Library of Medicine Medical Subject Headings (MeSH)