Hormone-sensitive lipase
Hormone-sensitive lipase (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]
Function
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.[5][6]
HSL is activated when the body needs to mobilize energy stores, and so responds positively to catecholamines, ACTH, and negatively to 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.[7]
Activation
It may be activated by two mechanisms.[8]
- 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.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=46620.
- ^ 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". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3991.
- ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1174508.
- ^ [|de Meijer J] (1998-05-01). Hormone sensitive lipase: structure, function and regulation. demeijer.com. http://demeijer.com/biology/scriptie.pdf. 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.
- ^ 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=46620.
- 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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=21893.
- 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. 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. PMID 11979403.
External links
|
|
|
| 3.1.1: Carboxylic ester hydrolases |
Cholinesterase (Acetylcholinesterase, Butyrylcholinesterase) · Pectinesterase · 6-phosphogluconolactonase · PAF acetylhydrolase
Lipase (Bile salt-dependent, Gastric/Lingual, Pancreatic, Lysosomal, Hormone-sensitive, Endothelial, Hepatic, Lipoprotein, Monoacylglycerol, Diacylglycerol)
Phospholipase ( A1, A2, B)
|
|
| 3.1.2: Thioesterase |
|
|
| 3.1.3: Phosphatase |
|
|
| 3.1.4: Phosphodiesterase |
|
|
| 3.1.6: Sulfatase |
|
|
Nuclease (includes
deoxyribonuclease and
ribonuclease) |
|
|
|
B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6
|
|