Assembly of active LPL and LIPC lipase complexes

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R-HSA-8963889
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Pathway
Species
Homo sapiens
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Lipoprotein lipase (LPL) and hepatic triacylglycerol lipase (LIPC) enzymes on the lumenal surfaces of capillary endothelia mediate the hydrolysis of triglyceride molecules in circulating lipoprotein particles.
LPL is widely expressed in the body and is especially abundant in adipocytes and skeletal and cardiac myocytes. Activation of the protein requires glycosylation, dimerization, and glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), which delivers it to heparan sulfate proteoglycan (HSPG) associated with the plasma membrane. It is inactivated by proteolytic cleavage (Berryman & Bensadoun 1995; Sukonina et al. 2006; Young et al. 2011).
Expression of the LPL gene is transcriptionally regulated by Cyclic AMP-responsive element-binding protein 3-like protein 3 (CREB3L3), which also regulates the expression of APOA4, APOA5, APOC2, CIDEC and FGF21 (Lee et al. 2011).
Maturation of LIPC enzyme requires association with LMF1 protein (or possibly, inferred from sequence similarity, LMF2). Heparin binding stabilizes LIPC in its active dimeric form (Babilonia-Rosa & Neher 2014; Ben-Zeev et al. 2011).

Literature References
PubMed ID Title Journal Year
7592670 Heparan sulfate proteoglycans are primarily responsible for the maintenance of enzyme activity, binding, and degradation of lipoprotein lipase in Chinese hamster ovary cells

Berryman, DE, Bensadoun, A

J. Biol. Chem. 1995
17088546 Angiopoietin-like protein 4 converts lipoprotein lipase to inactive monomers and modulates lipase activity in adipose tissue

Sukonina, V, Lookene, A, Olivecrona, T, Olivecrona, G

Proc. Natl. Acad. Sci. U.S.A. 2006
21844202 GPIHBP1, an endothelial cell transporter for lipoprotein lipase

Young, SG, Davies, BS, Voss, CV, Gin, P, Weinstein, MM, Tontonoz, P, Reue, K, Bensadoun, A, Fong, LG, Beigneux, AP

J. Lipid Res. 2011
21666694 The transcription factor cyclic AMP-responsive element-binding protein H regulates triglyceride metabolism

Lee, JH, Giannikopoulos, P, Duncan, SA, Wang, J, Johansen, CT, Brown, JD, Plutzky, J, Hegele, RA, Glimcher, LH, Lee, AH

Nat. Med. 2011
21447484 Lipase maturation factor 1 is required for endothelial lipase activity

Ben-Zeev, O, Hosseini, M, Lai, CM, Ehrhardt, N, Wong, H, Cefalù, AB, Noto, D, Averna, MR, Doolittle, MH, Péterfy, M

J. Lipid Res. 2011
24909692 Purification, cellular levels, and functional domains of lipase maturation factor 1

Babilonia-Rosa, MA, Neher, SB

Biochem. Biophys. Res. Commun. 2014
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