Hormone-sensitive lipase: Difference between revisions
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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> | '''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> | 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> | ||
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== Function == | == 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 ( | 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 (ATGL), has a higher affinity for triglycerides than HSL, and ATGL predominantly 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}} | 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 | Another important role is the release of cholesterol from cholesteryl 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> and cholesterol efflux.<ref name="Cholesterol efflux in Macrophages review">{{cite journal | vauthors= Ouimet M, Marcel YL | title = Regulation of Lipid Droplet Cholesterol Efflux From Macrophage Foam Cells | journal = Arterioscler. Thromb. Vasc. Biol. | volume = 32| pages = 575–581 |date=February 2012 | pmid = 17208360| doi = 10.1161/ATVBAHA.111.240705}}</ref> Activity of HSL is important in preventing or ameliorating the generation of [[foam cell]]s in [[atherosclerosis]].<ref name="Cholesterol efflux in Macrophages review"/> | ||
== Activation == | == Activation == | ||
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* 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. | * 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]]. | * 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, stimulation of the [[glucagon receptor]] and [[ACTH]] stimulation of the [[ACTH receptor]] in the [[Adrenal#Cortex|adrenal cortex]]. | ||
== References == | == References == | ||
Latest revision as of 08:14, 27 October 2018
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| Hormone-sensitive lipase (HSL) N-terminus | |||||||||
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| Symbol | HSL_N | ||||||||
| Pfam | PF06350 | ||||||||
| InterPro | IPR010468 | ||||||||
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Hormone-sensitive lipase (EC 3.1.1.79, HSL), also previously known as cholesteryl ester hydrolase (CEH),[1] is an enzyme that, in humans, is encoded by the LIPE gene.[2]
HSL is an intracellular neutral lipase that is capable of hydrolyzing a variety of esters.[3] 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.[4]
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".[5] 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.
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 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 (ATGL), has a higher affinity for triglycerides than HSL, and ATGL predominantly 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.[6][7]
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]
Another important role is the release of cholesterol from cholesteryl esters for use in the production of steroids[8] and cholesterol efflux.[9] Activity of HSL is important in preventing or ameliorating the generation of foam cells in atherosclerosis.[9]
Activation
It may be activated by two mechanisms.[10]
- 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 protein-coupled receptors that promote cAMP production. Examples include beta adrenergic stimulation, stimulation of the glucagon receptor and ACTH stimulation of the ACTH receptor in the adrenal cortex.
References
- ↑ 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". Biol. Reprod. 53 (5): 1110–7. doi:10.1095/biolreprod53.5.1110. PMID 8527515.
- ↑ 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". Proc. Natl. Acad. Sci. U.S.A. 90 (11): 4897–901. doi:10.1073/pnas.90.11.4897. PMC 46620. PMID 8506334.
- ↑ Kraemer FB, Shen WJ (October 2002). "Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis". J. Lipid Res. 43 (10): 1585–94. doi:10.1194/jlr.R200009-JLR200. PMID 12364542.
- ↑ "Entrez Gene: LIPE lipase, hormone-sensitive".
- ↑ Kraemer FB, Shen WJ (October 2002). "Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis". J. Lipid Res. 43 (10): 1585–94. doi:10.1194/jlr.R200009-JLR200. PMID 12364542.
- ↑ Crabtree B, Newsholme EA (December 1972). "The activities of lipases and carnitine palmitoyltransferase in muscles from vertebrates and invertebrates". Biochem. J. 130 (3): 697–705. PMC 1174508. PMID 4664927.
- ↑ de Meijer J (1998-05-01). "Hormone sensitive lipase: structure, function and regulation" (PDF). demeijer.com. Retrieved 2009-02-04.
- ↑ Kraemer FB (February 2007). "Adrenal cholesterol utilization". Mol. Cell. Endocrinol. 265-266: 42–5. doi:10.1016/j.mce.2006.12.001. PMID 17208360.
- ↑ 9.0 9.1 Ouimet M, Marcel YL (February 2012). "Regulation of Lipid Droplet Cholesterol Efflux From Macrophage Foam Cells". Arterioscler. Thromb. Vasc. Biol. 32: 575–581. doi:10.1161/ATVBAHA.111.240705. PMID 17208360.
- ↑ Cox, Michael; Nelson, David R.; Lehninger, Albert L (2005). Lehninger principles of biochemistry. San Francisco: W.H. Freeman. ISBN 0-7167-4339-6.
Further reading
- Kraemer FB, Shen WJ (2003). "Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis". J. Lipid Res. 43 (10): 1585–94. doi:10.1194/jlr.R200009-JLR200. PMID 12364542.
- Langfort J, Donsmark M, Ploug T, et al. (2003). "Hormone-sensitive lipase in skeletal muscle: regulatory mechanisms". Acta Physiol. Scand. 178 (4): 397–403. doi:10.1046/j.1365-201X.2003.01155.x. PMID 12864745.
- Holm C (2004). "Molecular mechanisms regulating hormone-sensitive lipase and lipolysis". Biochem. Soc. Trans. 31 (Pt 6): 1120–4. doi:10.1042/BST0311120. PMID 14641008.
- Holm C, Kirchgessner TG, Svenson KL, et al. (1988). "Hormone-sensitive lipase: sequence, expression, and chromosomal localization to 19 cent-q13.3". Science. 241 (4872): 1503–6. doi:10.1126/science.3420405. PMID 3420405.
- Levitt RC, Liu Z, Nouri N, et al. (1995). "Mapping of the gene for hormone sensitive lipase (LIPE) to chromosome 19q13.1→q13.2". Cytogenet. Cell Genet. 69 (3–4): 211–4. doi:10.1159/000133966. PMID 7698015.
- Langin D, Laurell H, Holst LS, et al. (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". Proc. Natl. Acad. Sci. U.S.A. 90 (11): 4897–901. doi:10.1073/pnas.90.11.4897. PMC 46620. PMID 8506334.
- Holst LS, Langin D, Mulder H, et al. (1996). "Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase". Genomics. 35 (3): 441–7. doi:10.1006/geno.1996.0383. PMID 8812477.
- Anthonsen MW, Rönnstrand L, Wernstedt C, et al. (1998). "Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro". J. Biol. Chem. 273 (1): 215–21. doi:10.1074/jbc.273.1.215. PMID 9417067.
- Shen WJ, Sridhar K, Bernlohr DA, Kraemer FB (1999). "Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein". Proc. Natl. Acad. Sci. U.S.A. 96 (10): 5528–32. doi:10.1073/pnas.96.10.5528. PMC 21893. PMID 10318917.
- Syu LJ, Saltiel AR (1999). "Lipotransin: a novel docking protein for hormone-sensitive lipase". Mol. Cell. 4 (1): 109–15. doi:10.1016/S1097-2765(00)80192-6. PMID 10445032.
- Shen WJ, Patel S, Hong R, Kraemer FB (2000). "Hormone-sensitive lipase functions as an oligomer". Biochemistry. 39 (9): 2392–8. doi:10.1021/bi992283h. PMID 10694408.
- Johnson WJ, Jang SY, Bernard DW (2001). "Hormone sensitive lipase mRNA in both monocyte and macrophage forms of the human THP-1 cell line". Comp. Biochem. Physiol. B, Biochem. Mol. Biol. 126 (4): 543–52. doi:10.1016/S0305-0491(00)00220-0. PMID 11026666.
- Laurin NN, Wang SP, Mitchell GA (2001). "The hormone-sensitive lipase gene is transcribed from at least five alternative first exons in mouse adipose tissue". Mamm. Genome. 11 (11): 972–8. doi:10.1007/s003350010185. PMID 11063252.
- Greenberg AS, Shen WJ, Muliro K, et al. (2002). "Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal-regulated kinase pathway". J. Biol. Chem. 276 (48): 45456–61. doi:10.1074/jbc.M104436200. PMID 11581251.
- Talmud PJ, Palmen J, Luan J, et al. (2002). "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". Biochim. Biophys. Acta. 1537 (3): 239–44. doi:10.1016/s0925-4439(01)00076-x. PMID 11731226.
- Kolehmainen M, Vidal H, Ohisalo JJ, et al. (2002). "Hormone sensitive lipase expression and adipose tissue metabolism show gender difference in obese subjects after weight loss". Int. J. Obes. Relat. Metab. Disord. 26 (1): 6–16. doi:10.1038/sj.ijo.0801858. PMID 11791141.
- Smih F, Rouet P, Lucas S, et al. (2002). "Transcriptional regulation of adipocyte hormone-sensitive lipase by glucose". Diabetes. 51 (2): 293–300. doi:10.2337/diabetes.51.2.293. PMID 11812735.
- Mairal A, Melaine N, Laurell H, et al. (2002). "Characterization of a novel testicular form of human hormone-sensitive lipase". Biochem. Biophys. Res. Commun. 291 (2): 286–90. doi:10.1006/bbrc.2002.6427. PMID 11846402.
- Ylitalo K, Nuotio I, Viikari J, et al. (2002). "C3, hormone-sensitive lipase, and peroxisome proliferator-activated receptor gamma expression in adipose tissue of familial combined hyperlipidemia patients". Metab. Clin. Exp. 51 (5): 664–70. doi:10.1053/meta.2002.32032. PMID 11979403.
External links
- Hormone-Sensitive+Lipase at the US National Library of Medicine Medical Subject Headings (MeSH)