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[[Image:HPL_Movie0006.png|300 px|left|thumb|Hormone-Sensitive Lipase]] | [[Image:HPL_Movie0006.png|300 px|left|thumb|Hormone-Sensitive Lipase]] | ||
| - | Hormone-sensitive [http://proteopedia.org/wiki/index.php/Lipase lipases] 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 [http://en.wikipedia.org/wiki/Catecholamine catecholamines] and inhibited by [http://www.proteopedia.org/wiki/index.php/Insulin insulin]. Briefly, binding of catecholamines to β-adrenergic receptors coupled with [http://www.proteopedia.org/wiki/index.php/Adenylate_Cyclase adenylate cyclase] (AC) stimulates G-proteins to increase the levels of cystolic [http://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate cAMP]. Elevated levels of cAMP leads to an activation [http://www.proteopedia.org/wiki/index.php/Protein_kinase_A 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. <ref name="Holm">PMID:14641008</ref> | + | Hormone-sensitive [http://proteopedia.org/wiki/index.php/Lipase 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 [http://en.wikipedia.org/wiki/Catecholamine catecholamines] and inhibited by [http://www.proteopedia.org/wiki/index.php/Insulin insulin]. Briefly, binding of catecholamines to β-adrenergic receptors coupled with [http://www.proteopedia.org/wiki/index.php/Adenylate_Cyclase adenylate cyclase] (AC) stimulates G-proteins to increase the levels of cystolic [http://en.wikipedia.org/wiki/Cyclic_adenosine_monophosphate cAMP]. Elevated levels of cAMP leads to an activation [http://www.proteopedia.org/wiki/index.php/Protein_kinase_A 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. <ref name="Holm">PMID:14641008</ref> |
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==Structure of hormone-sensitive lipase== | ==Structure of hormone-sensitive lipase== | ||
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| - | <ref name="Nam">PMID:19089974</ref> | ||
<StructureSection load='3DNM' size='350' frame='true' align='right' caption='Hormone-Sensitive Lipase from [[3dnm]]' scene='58/580297/3dnm_cartoon/2' > | <StructureSection load='3DNM' size='350' frame='true' align='right' caption='Hormone-Sensitive Lipase from [[3dnm]]' scene='58/580297/3dnm_cartoon/2' > | ||
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| + | <scene name='58/580297/3dnm_cartoon/2'>Hormone-sensitive lipases</scene> are generally well-conserved across species. HSL is composed of two main structural domains, consisting of a slightly variable N-terminus that is thought to contribute to numerous factors including activity, specificity, regioselectivity, thermophilicity, and thermostability. The second, highly conserved, domain of HSL is the C-terminal catalytic domain, which contains the catalytic triad. Size-exclusion chromatography studies have shown that HSL has a ligand pocket that is approximately 16Å deep, suggesting that HSL primarily hydrolyzes shorter chained molecules. <ref name="Nam">PMID:19089974</ref> | ||
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| + | The <scene name='58/580297/3dnm_ligandsite_charge_relay/1'>catalytic triad</scene> is comprised of Ser157, Glu251, and His281. The Ser157 residue sits at a site deemed the "nucleophile elbow," that models an approximate torsion of Φ = 60° and Ψ =-120°. This nucleophilic elbow is stabilized by a hydrogen bond between the proximal nitrogen and oxygen atoms of His281 and Glu251, respectively. This model also shows the Ser157 residue to be stabilized by the covalent binding of <scene name='58/580297/3dnm_cartoon_ligand/2'>β-mercaptoethanol</scene>. | ||
<scene name='58/580297/3dnm_cartoon/4'>default view</scene> | <scene name='58/580297/3dnm_cartoon/4'>default view</scene> | ||
| - | <scene name='58/580297/3dnm_cartoon/2'>hormone-sensitive lipase</scene> | ||
| - | <scene name='58/580297/3dnm_cartoon_ligand/2'> | + | |
| + | <scene name='58/580297/3dnm_cartoon_ligand/2'>β-mercaptoethanol</scene> | ||
<scene name='58/580297/3dnm_ligandsite_charge_relay/1'>triad</scene> | <scene name='58/580297/3dnm_ligandsite_charge_relay/1'>triad</scene> | ||
Revision as of 23:47, 26 March 2014
Contents |
Introduction to hormone-sensitive lipase
Image:HPL Movie0006.png
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. 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. [1]
Structure of hormone-sensitive lipase
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Inhibition of Hormone-Sensitive Lipase
Medical Relevance of Hormone-Sensitive Lipase
Additional Pages about Hormone-Sensitive Lipase
References
- ↑ 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
