Jump to content

Hormone-sensitive lipase

From Wikipedia, the free encyclopedia
(Redirected from LIPE (gene))
LIPE
Identifiers
AliasesLIPE, AOMS4, FPLD6, HSL, LHS, lipase E, hormone sensitive type, REH
External IDsOMIM: 151750; MGI: 96790; HomoloGene: 3912; GeneCards: LIPE; OMA:LIPE - orthologs
Orthologs
SpeciesHumanMouse
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 MbChr 7: 25.08 – 25.1 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
Hormone-sensitive lipase (HSL) N-terminus
Identifiers
SymbolHSL_N
PfamPF06350
InterProIPR010468
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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

[edit]

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

[edit]

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

[edit]

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

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000079435 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000003123 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Aten RF, Kolodecik TR, Macdonald GJ, Behrman HR (November 1995). "Modulation of cholesteryl ester hydrolase messenger ribonucleic acid levels, protein levels, and activity in the rat corpus luteum". Biology of Reproduction. 53 (5): 1110–7. doi:10.1095/biolreprod53.5.1110. PMID 8527515.
  6. ^ Langin D, Laurell H, Holst LS, Belfrage P, Holm C (June 1993). "Gene organization and primary structure of human hormone-sensitive lipase: possible significance of a sequence homology with a lipase of Moraxella TA144, an antarctic bacterium". Proceedings of the National Academy of Sciences of the United States of America. 90 (11): 4897–901. Bibcode:1993PNAS...90.4897L. doi:10.1073/pnas.90.11.4897. PMC 46620. PMID 8506334.
  7. ^ Kraemer FB, Shen WJ (October 2002). "Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis". Journal of Lipid Research. 43 (10): 1585–94. doi:10.1194/jlr.R200009-JLR200. PMID 12364542.
  8. ^ "Entrez Gene: LIPE lipase, hormone-sensitive".
  9. ^ Kraemer FB, Shen WJ (October 2002). "Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis". Journal of Lipid Research. 43 (10): 1585–94. doi:10.1194/jlr.R200009-JLR200. PMID 12364542.
  10. ^ Cox M, Nelson DR, Lehninger AL (2005). Lehninger principles of biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-4339-6.
  11. ^ a b Khoo JC, Aquino AA, Steinberg D (April 1974). "The mechanism of activation of hormone-sensitive lipase in human adipose tissue". The Journal of Clinical Investigation. 53 (4): 1124–31. doi:10.1172/JCI107650. PMC 333098. PMID 4360857.
  12. ^ a b Quinn DM, Medhekar R, Baker NR (1999). "Ester Hydrolysis". Comprehensive Natural Products Chemistry. pp. 101–137. doi:10.1016/B978-0-08-091283-7.00110-7. ISBN 978-0-08-091283-7.
  13. ^ Mehta S (October 2013). "Mobilization and Cellular Uptake of Stored Fats (Triacylglycerols) with Animation". Animations, Biochemistry Animations, Biochemistry Notes. PharmaXChange.info. Retrieved 2020-04-02.
  14. ^ Crabtree B, Newsholme EA (December 1972). "The activities of lipases and carnitine palmitoyltransferase in muscles from vertebrates and invertebrates". The Biochemical Journal. 130 (3): 697–705. doi:10.1042/bj1300697. PMC 1174508. PMID 4664927.
  15. ^ de Meijer J (1998-05-01). "Hormone sensitive lipase: structure, function and regulation" (PDF). demeijer.com. Retrieved 2009-02-04. {{cite journal}}: Cite journal requires |journal= (help)
  16. ^ Kraemer FB (February 2007). "Adrenal cholesterol utilization". Molecular and Cellular Endocrinology. 265–266: 42–5. doi:10.1016/j.mce.2006.12.001. PMID 17208360. S2CID 35354595.
  17. ^ a b Ouimet M, Marcel YL (March 2012). "Regulation of lipid droplet cholesterol efflux from macrophage foam cells". Arteriosclerosis, Thrombosis, and Vascular Biology. 32 (3): 575–81. doi:10.1161/ATVBAHA.111.240705. PMID 22207731.

Further reading

[edit]
[edit]
Retrieved from "https://wiki.riteme.site/w/index.php?title=Hormone-sensitive_lipase&oldid=1222299857"