Hormone sensitive lipase

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This page, as it appeared on May 3, 2014, was featured in this article in the journal Biochemistry and Molecular Biology Education.


Hormone-Sensitive Lipase from 3dnm. Alpha helices and beta sheets are shown in red and yellow, respectively.
Hormone-Sensitive Lipase from 3dnm. Alpha helices and beta sheets are shown in red and yellow, respectively.

Hormone-sensitive lipases (HSL) represent a class of esterases within the α/β hydrolase family. Like other lipases, HSL catalyzes the cleavage of ester bonds, releasing fatty acid molecules. The activation and mobilization of hormone-sensitive lipase can be triggered by various catecholamines and inhibited by insulin.[1][2] Catecholamines, such as epinephrine, are rapidly spread throughout the body during times of energy mobilization, like in the fight or flight response. Conversely, insulin triggers glucose uptake, requiring the storage of energy, opposing HSL's function. HSL is clinically relevant, because the mobilization of or inability to mobilize fats in cells is directly related to fat accumulation seen in artherosclerosisand obesity.[3] Such diseases are characterized by an accumulation of fats and researchers are investigating whether HSL's activity plays a role or not.[2] Investigation of HSL's structure and function could provide a better clinical understanding of these diseases.[3]

Activation of HSL

Briefly, HSL is stimulated by the binding of catecholamines to β-adrenergic receptors. β-adrenergic receptors coupled with adenylate cyclase (AC) then stimulate G-proteins to increase the levels of cystolic cAMP. Elevated levels of cAMP leads to an activation protein kinase A (PKA) leading to phosphorylation of serine residues on HSL activating and translocating HSL to lipid droplets for lipolysis. Conversely, insulin signaling decreases cystolic cAMP levels, resulting in a decreased HSL mobilization.[1]

Structure of hormone-sensitive lipase

Hormone-Sensitive Lipase (PDB: 3dnm)

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References

  1. 1.0 1.1 Holm C. Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans. 2003 Dec;31(Pt 6):1120-4. PMID:14641008 doi:http://dx.doi.org/10.1042/
  2. 2.0 2.1 Ray H, Beylot M, Arner P, Larrouy D, Langin D, Holm C, Large V. The presence of a catalytically inactive form of hormone-sensitive lipase is associated with decreased lipolysis in abdominal subcutaneous adipose tissue of obese subjects. Diabetes. 2003 Jun;52(6):1417-22. PMID:12765952
  3. 3.0 3.1 3.2 3.3 3.4 Yeaman SJ. Hormone-sensitive lipase--new roles for an old enzyme. Biochem J. 2004 Apr 1;379(Pt 1):11-22. PMID:14725507 doi:http://dx.doi.org/10.1042/BJ20031811
  4. 4.0 4.1 4.2 4.3 4.4 Nam KH, Kim MY, Kim SJ, Priyadarshi A, Kwon ST, Koo BS, Yoon SH, Hwang KY. Structural and functional analysis of a novel hormone-sensitive lipase from a metagenome library. Proteins. 2009 Mar;74(4):1036-40. PMID:19089974 doi:http://dx.doi.org/10.1002/prot.22313
  5. 5.0 5.1 Kanwar SS, Kaushal RK, Jawed A, Gupta R, Chimni SS. Methods for inhibition of residual lipase activity in colorimetric assay: a comparative study. Indian J Biochem Biophys. 2005 Aug;42(4):233-7. PMID:23923547
  6. 6.0 6.1 Nam KH, Kim SJ, Priyadarshi A, Kim HS, Hwang KY. The crystal structure of an HSL-homolog EstE5 complex with PMSF reveals a unique configuration that inhibits the nucleophile Ser144 in catalytic triads. Biochem Biophys Res Commun. 2009 Nov 13;389(2):247-50. Epub 2009 Aug 26. PMID:19715665 doi:10.1016/j.bbrc.2009.08.123
  7. Kraemer FB, Shen WJ. Hormone-sensitive lipase: control of intracellular tri-(di-)acylglycerol and cholesteryl ester hydrolysis. J Lipid Res. 2002 Oct;43(10):1585-94. PMID:12364542

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