User:Giselle Flores/Sandbox 1
From Proteopedia
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| - | =Lipoprotein Lipase = | + | Giselle’s Edit Box |
| - | + | =Lipoprotein Lipase LPL= | |
| - | + | <StructureSection load='6ob0' size='350' side='right' caption='Lipoprotein Lipase PDB' scene='87/877514/Intro_scene/3'> | |
| - | <StructureSection load='6ob0' size=' | + | |
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| + | You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue. | ||
==Introduction== | ==Introduction== | ||
| + | A [https://en.wikipedia.org/wiki/Lipase lipase] is an enzyme that is capable of catalyzing the [https://en.wikipedia.org/wiki/Hydrolysis hydrolysis] of fats/lipids which are consumed through oils. It is encoded by the [https://www.genecards.org/cgi-bin/carddisp.pl?gene=LPL p22 region in chromosome 8]. Once synthesized, it is secreted into the interstitial space in several tissues. The main site of action for LPL is in the [https://www.pnas.org/content/pnas/116/5/1480/F1.large.jpg capillary lumen] within muscle and adipose tissue. The function of this lipase is to hydrolyze [https://en.wikipedia.org/wiki/Triglyceride triglycerides] of very low density lipoproteins ([https://qph.fs.quoracdn.net/main-qimg-8e874e647baeb69b00203c47165247e2 VLDL]) and to aid in the delivery of lipid nutrients to vital tissues. The enzyme is commonly found on the surface of cells that line blood capillaries. Two different lipoproteins are essential to break down triglycerides. One of the lipoproteins is utilized to transport fat into the bloodstream from different organs. The lipoproteins essential, in the transport of fat from the intestine are referred to as [https://en.wikipedia.org/wiki/Chylomicron chylomicrons]. VLDL are utilized in carrying triglycerides from the liver into the bloodstream. The hydrolysis of triglycerides by lipoprotein lipase results in fat molecules to be used by the body as energy or stored in fatty tissue. [[Image:LLP11.jpg|300 px|left|thumb|LPL Image]] | ||
| - | A [https://en.wikipedia.org/wiki/Lipase lipase] is an enzyme that is capable of catalyzing the hydrolysis of fats/lipids which are consumed through oils. It is encoded by the [https://www.genecards.org/cgi-bin/carddisp.pl?gene=LPL p22 region in chromosome 8]. Once synthesized, it is secreted into the inter interstitial space in several tissues. The main site of action for LPL is in the [https://www.pnas.org/content/pnas/116/5/1480/F1.large.jpg capillary lumen] within muscle and adipose tissue. The function of this lipase is to hydrolyze triglycerides of very-low-density lipoproteins (VLDL) and to aid in the delivery of lipid nutrients to vital tissues. The enzyme is commonly found on the surface of cells that line blood capillaries. Two different lipoproteins are essential to break down triglycerides. One of the lipoproteins is utilized to transport fat into the bloodstream from different organs. The lipoproteins essential, in the transport of fat from the intestine, are referred to as chylomicrons. VLDL is utilized in carrying triglycerides from the liver into the bloodstream. The hydrolysis of triglycerides by lipoprotein lipase results in fat molecules being used by the body as energy or stored in fatty tissue. | ||
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| - | [[Image:LLP11.jpg|300 px|left|thumb|LPL Image]] | ||
==Structural Overview== | ==Structural Overview== | ||
| - | Lipoprotein Lipase is assumed to only be active as a <scene name='87/877513/Lpl_dimer/1'>homodimer</scene>, however, previous studies have argued that the lipase can be active in its | + | Lipoprotein Lipase is assumed to only be active as a <scene name='87/877513/Lpl_dimer/1'>homodimer</scene>, however, previous studies have argued that the lipase can be active in its monomeric form. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442593/) The N-terminal domain of lipoprotein lipase is known to consist of an alpha/beta hydrolase domain, which is composed of six alpha helices and ten beta-strands. This domain creates an <scene name='87/877513/Secondary_structure/1'>alpha/beta hydrolase fold</scene>. The C-terminal domain of lipoprotein lipase is composed of twelve beta strands which form a “<scene name='87/877513/Secondary_structure/1'>barrel domain |
| - | + | </scene>”. | |
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==Mechanism== | ==Mechanism== | ||
| - | Lipoprotein Lipase functions to catalyze the hydrolysis of one ester bond of triglycerides. It does this by utilizing a simple serine hydrolase mechanism, in which it uses a <scene name='87/877516/Catalytic_triad_master/1'>Catalytic Triad</scene> composed of Asp183, His268, and Ser159 to catalyze the hydrolysis. His268 serves as a base catalyst by | + | Lipoprotein Lipase functions to catalyze the hydrolysis of one [https://en.wikipedia.org/wiki/Ester ester bond] of triglycerides. It does this by utilizing a simple [ https://en.wikipedia.org/wiki/Serine_hydrolase serine hydrolase] mechanism, in which it uses a <scene name='87/877516/Catalytic_triad_master/1'>Catalytic Triad</scene> composed of Asp183, His268, and Ser159 to catalyze the hydrolysis. His268 serves as a base catalyst by deprotonation of Ser159, which can then serve as the [https://en.wikipedia.org/wiki/Nucleophile nucleophile]. The transition state of the catalysis is stabilized by the <scene name='87/877516/Oxyanion_hole_master/1'>Oxyanion Hole</scene> composed of Trp82 and Leu160. The hydrolysis results in the formation of one free fatty acid and a glycerol with two fatty acid tails. |
| + | [[Image:LPL_final_Mechanism.png|300 px|left|thumb|Serine hydrolase mechanism utilized by LPL to catalyze the breakdown of one ester bond of a triglyceride. Compounds colored red are the products of the hydrolysis.]] | ||
== Relevance & Disease == | == Relevance & Disease == | ||
| - | LPL is an extremely important enzyme, in that it breaks down triglycerides carried on VLDL, which leads to the reduction of cholesterol buildup. Cholesterol build | + | LPL is an extremely important enzyme, in that it breaks down triglycerides carried on VLDL, which leads to the reduction of [https://en.wikipedia.org/wiki/Cholesterol cholesterol] buildup. Cholesterol build up is a very serious issue with regards to obesity in the United States. In addition to this, increased plasma triglyceride levels ([https://en.wikipedia.org/wiki/Hypertriglyceridemia hypertriglyceridemia]) is very unhealthy and is the leading cause of [https://my.clevelandclinic.org/health/diseases/16898-coronary-artery-disease Coronary Artery Disease] in America. LPL is an enzyme that helps combat this disease by breaking down the excess triglycerides that block the arteries of your heart. Very similarly, [https://medlineplus.gov/ency/article/000405.htm Chylomicronemia], a high level of triglycerides in the blood, causes buildup of chylomicrons (ultra-low-density lipoproteins) and leads to similar diseases. Without LPL in the body, developing coronary & metabolic (liver & pancreas) based diseases are at a higher likelihood. |
| - | [[Image:M404_No_Mutation_copy.jpg| | + | |
| - | [[Image:M404ToR404Pymol_copy_2.jpg| | + | [[Image:M404_No_Mutation_copy.jpg|400 px|right|thumb|No Mutation Image]] |
| - | + | [[Image:M404ToR404Pymol_copy_2.jpg|400 px|right|thumb|Mutation Image]] | |
== Structural highlights == | == Structural highlights == | ||
| + | Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein ([https://en.wikipedia.org/wiki/GPIHBP1 GPIHBP1]) is necessary for LPL function and stability. (LIVE REFERENCED NEEDED) | ||
| + | [[Image:LLP11.jpg|300 px|left|thumb|LPL Image]] | ||
| + | Calcium ion stabilization, lid | ||
| - | Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein ([https://en.wikipedia.org/wiki/GPIHBP1 GPIHBP1]) is necessary for LPL function and stability. | ||
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| - | (LIVE REFERENCED NEEDED) | ||
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| - | <scene name='87/877514/Lpl_chaina_gf/1'>LPL Chain A</scene> | ||
== References == | == References == | ||
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<references/> | <references/> | ||
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<ref name=”Arora”>PMID:31072929</ref> | <ref name=”Arora”>PMID:31072929</ref> | ||
<ref name=”Birrane”>PMID:30559189</ref> | <ref name=”Birrane”>PMID:30559189</ref> | ||
<ref name=”Davies”>PMID:20620994</ref> | <ref name=”Davies”>PMID:20620994</ref> | ||
<ref name=”Beigneux”>PMID:30850549</ref> | <ref name=”Beigneux”>PMID:30850549</ref> | ||
| + | <ref name=”Mead”>PMID:12483461</ref> (LPL GENERAL REFERENCE) | ||
| + | <ref name=”Eckel”>PMID:2648155</ref> (LPL GENERAL REFERENCE BOOK IF NEEDED) | ||
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| - | <scene name='87/877514/__yup__/1'>yup</scene> | ||
==Student Contributors== | ==Student Contributors== | ||
Revision as of 18:32, 19 April 2021
Giselle’s Edit Box
Lipoprotein Lipase LPL
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