Reactome | Assembly of active LPL and LIPC lipase complexes

Assembly of active LPL and LIPC lipase complexes

Stable Identifier

R-HSA-8963889

Type

Pathway

Species

Homo sapiens

ReviewStatus

5/5

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Assembly of active LPL and LIPC lipase complexes

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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).

Literature References

PubMed ID	Title	Journal	Year
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
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
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
24909692	Purification, cellular levels, and functional domains of lipase maturation factor 1 Babilonia-Rosa, MA, Neher, SB	Biochem. Biophys. Res. Commun.	2014
30288870	Characterization of a peptide containing the major heparin binding domain of human hepatic lipase Coady, BM, Marshall, JD, Hattie, LE, Brannan, AM, Fitzpatrick, MN, Hickey, KE, Wallin, S, Booth, V, Brown, RJ	J Pept Sci	2018