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==Inhibition of hormone-sensitive lipase== | ==Inhibition of hormone-sensitive lipase== | ||
| + | Hormone-sensitive lipase can be inhibited by phenylmethylsufonyl flouride ([http://en.wikipedia.org/wiki/PMSF PMSF]) entering into the <scene name='58/580296/Meshligand/2'>active site</scene>. PMSF inhibits enzymes by binding to the SER residue of the [http://proteopedia.org/wiki/index.php/Serine_Proteases serine protease] active sites so that the normal catalytic activity cannot be carried out. This inhibitor will only bind to the active site SER because of its participation in the charge relay of the <scene name='58/580296/Meshligandinteraction/1'>catalytic triad</scene>. This hyper activity allows the sulfonyl group of PMSF to <scene name='58/580296/Inhibitorinteraction/4'>covalently bond</scene> to the SER residue to disrupt its activity. Because of this SER residue specificity, PMSF does not inhibit all kinds of lipases, just those dependent on SER residues in the active site. PMSF is highly degradable in aqueous solutions so it does not inhibit for very long periods of time in its natural environment. PMSF binding induces only a minor conformational change from the native protein.<ref name="Kanwar">PMID:23923547</ref> | ||
| + | Inhibition or decreased activity of hormone-sensitive lipases can possibly lead to disorders such as obesity and type 2 diabetes. Inability to break down fatty acid molecules due to inactive hormone-sensitive lipases has been reported in many cases of obesity and type 2 diabetes. Increased inhibition of HSL by PMSF could, in theory, also be a possible cause of these diseases.<ref name="Kraemer">PMID: 12364542 </ref> | ||
==Additional pages about hormone-sensitive lipase== | ==Additional pages about hormone-sensitive lipase== | ||
* [http://en.wikipedia.org/wiki/Hormone_sensitive_lipase Hormone-sensitive lipase] | * [http://en.wikipedia.org/wiki/Hormone_sensitive_lipase Hormone-sensitive lipase] | ||
Revision as of 02:21, 1 April 2014
Contents |
Introduction to hormone-sensitive lipase
Hormone-sensitive lipases (HSL) represent a class of esterases within the hydrolase family that catalyzes the cleavage of ester bonds in fatty acid molecules when stimulated by a hormone. The activation and mobilization of these hormone-sensitive lipases can be triggered by various catecholamines and inhibited by insulin. HSL is clinically relevant because the mobilization of fats in cells is directly related to fat accumulation seen in atherosclerosis, diabetes, and obesity. Investigation of HSL's structure and function could provide a better clinical understanding of these diseases. [1]
Briefly, binding of catecholamines to β-adrenergic receptors coupled with adenylate cyclase (AC) stimulates 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. [2]
Structure of hormone-sensitive lipase
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Inhibition of hormone-sensitive lipase
Hormone-sensitive lipase can be inhibited by phenylmethylsufonyl flouride (PMSF) entering into the . PMSF inhibits enzymes by binding to the SER residue of the serine protease active sites so that the normal catalytic activity cannot be carried out. This inhibitor will only bind to the active site SER because of its participation in the charge relay of the . This hyper activity allows the sulfonyl group of PMSF to to the SER residue to disrupt its activity. Because of this SER residue specificity, PMSF does not inhibit all kinds of lipases, just those dependent on SER residues in the active site. PMSF is highly degradable in aqueous solutions so it does not inhibit for very long periods of time in its natural environment. PMSF binding induces only a minor conformational change from the native protein.[4]
Inhibition or decreased activity of hormone-sensitive lipases can possibly lead to disorders such as obesity and type 2 diabetes. Inability to break down fatty acid molecules due to inactive hormone-sensitive lipases has been reported in many cases of obesity and type 2 diabetes. Increased inhibition of HSL by PMSF could, in theory, also be a possible cause of these diseases.[5]
Additional pages about hormone-sensitive lipase
References
- ↑ 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
- ↑ 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/
- ↑ 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
- ↑ 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
- ↑ 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
