Hormone-sensitive lipase

2017-09-28T01:19:05Z

67.231.194.61: /* Function */Added content

{{Infobox_gene}}
{{Pfam_box
| Symbol = HSL_N
| Name = Hormone-sensitive lipase (HSL) N-terminus
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| Pfam= PF06350
| InterPro= IPR010468
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'''Hormone-sensitive lipase''' ({{EC number|3.1.1.79}}, HSL) also previously known as cholesteryl ester hydrolase (CEH)<ref>{{cite journal |vauthors=Aten RF, Kolodecik TR, Macdonald GJ, Behrman HR | title = Modulation of cholesteryl ester hydrolase messenger ribonucleic acid levels, protein levels, and activity in the rat corpus luteum | journal = Biol. Reprod. | volume = 53| issue = 5 | pages = 1110–7 |date=November 1995 | pmid = 8527515 | doi = 10.1095/biolreprod53.5.1110 }}</ref> is an [[enzyme]] that, in humans, is encoded by the ''LIPE'' [[gene]].<ref name="pmid8506334">{{cite journal |vauthors=Langin D, Laurell H, Holst LS, Belfrage P, Holm C | title = 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 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 90 | issue = 11 | pages = 4897–901 |date=June 1993 | pmid = 8506334 | pmc = 46620 | doi = 10.1073/pnas.90.11.4897| url = }}</ref>

HSL is an intracellular neutral [[lipase]] that is capable of hydrolyzing a variety of [[ester]]s.<ref name="pmid12364542">{{cite journal |vauthors=Kraemer FB, Shen WJ | title = Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis | journal = J. Lipid Res. | volume = 43 | issue = 10 | pages = 1585–94 |date=October 2002 | pmid = 12364542 | doi = 10.1194/jlr.R200009-JLR200| url = }}</ref> The enzyme has a long and a short form. The long form is expressed in steroidogenic tissues such as [[testis]], where it converts [[cholesteryl ester]]s to free [[cholesterol]] for steroid hormone production. The short form is expressed in [[adipocytes|adipose]] tissue, among others, where it hydrolyzes stored [[triglyceride]]s to free [[fatty acid]]s.<ref name="entrez">{{cite web | title = Entrez Gene: LIPE lipase, hormone-sensitive| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3991| accessdate = }}</ref>

== Nomenclature ==
During fasting-state the increased [[Fatty acid#Free fatty acids|free fatty acid]] secretion by [[adipocyte]] cells was attributed to the hormone [[epinephrine]], hence the name "hormone-sensitive lipase".<ref>{{cite journal |vauthors=Kraemer FB, Shen WJ |title=Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis |journal=J. Lipid Res. |volume=43 |issue=10 |pages=1585–94 |date=October 2002 |pmid=12364542 |doi=10.1194/jlr.R200009-JLR200 |url=http://www.jlr.org/content/43/10/1585.long}}</ref> Other [[catecholamine]]s 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. [http://pharmaxchange.info/press/2013/10/mobilization-and-cellular-uptake-of-stored-fats-triacylglycerols-with-animation/ Mobilization and Cellular Uptake of Stored Fats (with Animation)] 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. Another enzyme found in adipose tissue, Adipose Triglyceride Lipase (ATGP), has a higher affinity for triglycerides than HSL, and ATGP predominately acts as the enzyme for triglyceride hydrolysis in the adipocyte. HSL 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.<ref name="pmid4664927">{{cite journal |vauthors=Crabtree B, Newsholme EA | title = The activities of lipases and carnitine palmitoyltransferase in muscles from vertebrates and invertebrates | journal = Biochem. J. | volume = 130 | issue = 3 | pages = 697–705 |date=December 1972 | pmid = 4664927 | pmc = 1174508 | doi = | url = | issn = }}</ref><ref name="urldemeijer.com">{{cite journal | author = de Meijer J | title = Hormone sensitive lipase: structure, function and regulation | publisher = demeijer.com | date = 1998-05-01 | url = http://demeijer.com/biology/scriptie.pdf | format = | accessdate = 2009-02-04 }}</ref>

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.{{Citation needed|reason=Reliable source needed for the whole paragraph|date=April 2013}}

Another important role is the release of cholesterol from cholesterol esters for use in the production of [[steroids]].<ref name="pmid17208360">{{cite journal | author = Kraemer FB | title = Adrenal cholesterol utilization | journal = Mol. Cell. Endocrinol. | volume = 265-266| pages = 42–5 |date=February 2007 | pmid = 17208360| doi = 10.1016/j.mce.2006.12.001}}</ref>

== Activation ==

It may be activated by two mechanisms.<ref name="isbn0-7167-4339-6">{{cite book |author1=Cox, Michael |author2=Nelson, David R. |author3=Lehninger, Albert L | title = Lehninger principles of biochemistry | edition = | language = | publisher = W.H. Freeman | location = San Francisco | year = 2005 | origyear = | pages = | quote = | isbn = 0-7167-4339-6 | oclc = | doi = | url = | accessdate = }}</ref>

* 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 [[Gs alpha subunit|G<sub>s</sub> 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|adrenal cortex]].

== References ==
{{reflist}}
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==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal |vauthors=Kraemer FB, Shen WJ |title=Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis. |journal=J. Lipid Res. |volume=43 |issue= 10 |pages= 1585–94 |year= 2003 |pmid= 12364542 |doi=10.1194/jlr.R200009-JLR200 }}
*{{cite journal |vauthors=Langfort J, Donsmark M, Ploug T, etal |title=Hormone-sensitive lipase in skeletal muscle: regulatory mechanisms. |journal=Acta Physiol. Scand. |volume=178 |issue= 4 |pages= 397–403 |year= 2003 |pmid= 12864745 |doi=10.1046/j.1365-201X.2003.01155.x }}
*{{cite journal | author=Holm C |title=Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. |journal=Biochem. Soc. Trans. |volume=31 |issue= Pt 6 |pages= 1120–4 |year= 2004 |pmid= 14641008 |doi= 10.1042/BST0311120 }}
*{{cite journal |vauthors=Holm C, Kirchgessner TG, Svenson KL, etal |title=Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 cent-q13.3. |journal=Science |volume=241 |issue= 4872 |pages= 1503–6 |year= 1988 |pmid= 3420405 |doi=10.1126/science.3420405 }}
*{{cite journal |vauthors=Levitt RC, Liu Z, Nouri N, etal |title=Mapping of the gene for hormone sensitive lipase (LIPE) to chromosome 19q13.1→q13.2. |journal=Cytogenet. Cell Genet. |volume=69 |issue= 3-4 |pages= 211–4 |year= 1995 |pmid= 7698015 |doi=10.1159/000133966 }}
*{{cite journal |vauthors=Langin D, Laurell H, Holst LS, etal |title=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. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=90 |issue= 11 |pages= 4897–901 |year= 1993 |pmid= 8506334 |doi=10.1073/pnas.90.11.4897 | pmc=46620 }}
*{{cite journal |vauthors=Holst LS, Langin D, Mulder H, etal |title=Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase. |journal=Genomics |volume=35 |issue= 3 |pages= 441–7 |year= 1996 |pmid= 8812477 |doi=10.1006/geno.1996.0383 }}
*{{cite journal |vauthors=Anthonsen MW, Rönnstrand L, Wernstedt C, etal |title=Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro. |journal=J. Biol. Chem. |volume=273 |issue= 1 |pages= 215–21 |year= 1998 |pmid= 9417067 |doi=10.1074/jbc.273.1.215 }}
*{{cite journal |vauthors=Shen WJ, Sridhar K, Bernlohr DA, Kraemer FB |title=Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 10 |pages= 5528–32 |year= 1999 |pmid= 10318917 |doi=10.1073/pnas.96.10.5528 | pmc=21893 }}
*{{cite journal |vauthors=Syu LJ, Saltiel AR |title=Lipotransin: a novel docking protein for hormone-sensitive lipase. |journal=Mol. Cell |volume=4 |issue= 1 |pages= 109–15 |year= 1999 |pmid= 10445032 |doi=10.1016/S1097-2765(00)80192-6 }}
*{{cite journal |vauthors=Shen WJ, Patel S, Hong R, Kraemer FB |title=Hormone-sensitive lipase functions as an oligomer. |journal=Biochemistry |volume=39 |issue= 9 |pages= 2392–8 |year= 2000 |pmid= 10694408 |doi=10.1021/bi992283h }}
*{{cite journal |vauthors=Johnson WJ, Jang SY, Bernard DW |title=Hormone sensitive lipase mRNA in both monocyte and macrophage forms of the human THP-1 cell line. |journal=Comp. Biochem. Physiol. B, Biochem. Mol. Biol. |volume=126 |issue= 4 |pages= 543–52 |year= 2001 |pmid= 11026666 |doi=10.1016/S0305-0491(00)00220-0 }}
*{{cite journal |vauthors=Laurin NN, Wang SP, Mitchell GA |title=The hormone-sensitive lipase gene is transcribed from at least five alternative first exons in mouse adipose tissue. |journal=Mamm. Genome |volume=11 |issue= 11 |pages= 972–8 |year= 2001 |pmid= 11063252 |doi=10.1007/s003350010185 }}
*{{cite journal |vauthors=Greenberg AS, Shen WJ, Muliro K, etal |title=Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal-regulated kinase pathway. |journal=J. Biol. Chem. |volume=276 |issue= 48 |pages= 45456–61 |year= 2002 |pmid= 11581251 |doi= 10.1074/jbc.M104436200 }}
*{{cite journal |vauthors=Talmud PJ, Palmen J, Luan J, etal |title=Variation in the promoter of the human hormone sensitive lipase gene shows gender specific effects on insulin and lipid levels: results from the Ely study. |journal=Biochim. Biophys. Acta |volume=1537 |issue= 3 |pages= 239–44 |year= 2002 |pmid= 11731226 |doi= 10.1016/s0925-4439(01)00076-x}}
*{{cite journal |vauthors=Kolehmainen M, Vidal H, Ohisalo JJ, etal |title=Hormone sensitive lipase expression and adipose tissue metabolism show gender difference in obese subjects after weight loss. |journal=Int. J. Obes. Relat. Metab. Disord. |volume=26 |issue= 1 |pages= 6–16 |year= 2002 |pmid= 11791141 |doi= 10.1038/sj.ijo.0801858 }}
*{{cite journal |vauthors=Smih F, Rouet P, Lucas S, etal |title=Transcriptional regulation of adipocyte hormone-sensitive lipase by glucose. |journal=Diabetes |volume=51 |issue= 2 |pages= 293–300 |year= 2002 |pmid= 11812735 |doi=10.2337/diabetes.51.2.293 }}
*{{cite journal |vauthors=Mairal A, Melaine N, Laurell H, etal |title=Characterization of a novel testicular form of human hormone-sensitive lipase. |journal=Biochem. Biophys. Res. Commun. |volume=291 |issue= 2 |pages= 286–90 |year= 2002 |pmid= 11846402 |doi= 10.1006/bbrc.2002.6427 }}
*{{cite journal |vauthors=Ylitalo K, Nuotio I, Viikari J, etal |title=C3, hormone-sensitive lipase, and peroxisome proliferator-activated receptor gamma expression in adipose tissue of familial combined hyperlipidemia patients. |journal=Metab. Clin. Exp. |volume=51 |issue= 5 |pages= 664–70 |year= 2002 |pmid= 11979403 |doi= 10.1053/meta.2002.32032}}
}}
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==External links==
* {{MeshName|Hormone-Sensitive+Lipase}}

{{Esterases}}


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[[Category:EC 3.1.1]]

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Hormone-sensitive lipase