spinqualitylabelsall models Lipoprotein Lipase Biological Assembly Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Contents 1 Introduction 2 Mechanism 3 Relevance & Disease 4 Structural highlights 5 References 6 Student Contributors

Introduction

LPL is a part of the lipase family. Lipases are enzymes that is capable of catalyzing the hydrolysis of fats/lipids which are consumed through oils. It is encoded by the 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 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 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. ^[1]

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 composed of Asp183, His268, and Ser159 to catalyze the hydrolysis. His268 serves as a base catalyst by deprotonating Ser159, which can then serve as the nucleophile. The transition state of the catalysis is stabilized by the composed of Trp82 and Leu160. The hydrolysis results in the formation of one free fatty acid and a glycerol with two fatty acid tails.

^[2]

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 up is a very serious issue with regards to obesity in the United States. In addition to this, increased plasma triglyceride levels (hypertriglyceridemia) is very unhealthy and is the leading cause of 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, 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.

Structural highlights

Image of N terminal with active site Image of C terminal domain Calcium

References

1. ↑ Arora R, Nimonkar AV, Baird D, Wang C, Chiu CH, Horton PA, Hanrahan S, Cubbon R, Weldon S, Tschantz WR, Mueller S, Brunner R, Lehr P, Meier P, Ottl J, Voznesensky A, Pandey P, Smith TM, Stojanovic A, Flyer A, Benson TE, Romanowski MJ, Trauger JW. Structure of lipoprotein lipase in complex with GPIHBP1. Proc Natl Acad Sci U S A. 2019 May 21;116(21):10360-10365. doi:, 10.1073/pnas.1820171116. Epub 2019 May 9. PMID:31072929 doi:http://dx.doi.org/10.1073/pnas.1820171116
2. ↑ Birrane G, Beigneux AP, Dwyer B, Strack-Logue B, Kristensen KK, Francone OL, Fong LG, Mertens HDT, Pan CQ, Ploug M, Young SG, Meiyappan M. Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis. Proc Natl Acad Sci U S A. 2018 Dec 17. pii: 1817984116. doi:, 10.1073/pnas.1817984116. PMID:30559189 doi:http://dx.doi.org/10.1073/pnas.1817984116

Student Contributors

• Giselle Flores
• Dustin Soe
• Maggie Stopa