Hormone-sensitive lipase

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Lipase, hormone-sensitive
Identifiers
Symbols LIPE ; HSL; LHS
External IDs OMIM151750 MGI96790 HomoloGene3912 ChEMBL: 3590 GeneCards: LIPE Gene
EC number 3.1.1.79
RNA expression pattern
PBB GE LIPE 208186 s at tn.png
PBB GE LIPE 213855 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3991 16890
Ensembl ENSG00000079435 ENSMUSG00000003123
UniProt Q05469 P54310
RefSeq (mRNA) NM_005357 NM_001039507
RefSeq (protein) NP_005348 NP_001034596
Location (UCSC) Chr 19:
42.91 – 42.93 Mb
Chr 7:
25.38 – 25.4 Mb
PubMed search [1] [2]
Hormone-sensitive lipase (HSL) N-terminus
Identifiers
Symbol HSL_N
Pfam PF06350
InterPro IPR010468

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[edit]

During fasting-state the increased free fatty acid secretion by adipocyte cells was attributed to epinephrine hormone. Hence the name "hormone-sensitive lipase".[5] Other hormones like 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[edit]

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 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.[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 cholesterol esters for use in the production of steroids.[8]

Activation[edit]

It may be activated by two mechanisms.[9]

  • 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[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ "Entrez Gene: LIPE lipase, hormone-sensitive". 
  5. ^ 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. 
  6. ^ 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. 
  7. ^ de Meijer J (1998-05-01). Hormone sensitive lipase: structure, function and regulation. demeijer.com. Retrieved 2009-02-04. 
  8. ^ 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. ^ 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[edit]

External links[edit]