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Pathway Description
Familial Lipoprotein Lipase Deficiency
Homo sapiens
Disease Pathway
Familial lipoprotein lipase deficiency (LPLD), also known as familial chylomicronemia syndrome, chylomicronemia, chylomicronemia syndrome, and hyperlipoproteinemia type Ia, is an extremely rare inherited inborn error of metabolism (IEM) of lipid metabolism. LPLD affects about 1 out of 1 000 000 people. It is an autosomal recessive disorder that is caused by a defect or deficiency in the enzyme lipoprotein lipase. Lipoprotein lipase is a water-soluble enzyme that hydrolyzes triglycerides in lipoproteins, such as those found in chylomicrons and very-low-density lipoproteins (VLDL), into two free fatty acids and one monoacylglycerol molecule. Defects in lipoprotein lipase will lead to accumulations of triglycerides and massive accumulation of fatty droplets called chylomicrons in the blood. As a result, LPLD is characterized by abnormally elevated levels of triglycerides and chylomicrons in serum and plasma (chylomicronemia). Affected individuals often experience episodes of abdominal pain, acute recurrent inflammation of the pancreas (pancreatitis), abnormal enlargement of the liver and/or spleen, and the development of skin lesions known as eruptive xanthomas. Most cases of LPLD are identified before the age of 10. In roughly one-quarter of patients, the disorder is identified during the first year of life. Some affected individuals may not be identified until adulthood. Treatment of LPLD is mainly based on medical nutrition therapy to maintain plasma triglyceride concentration below 11.3 mmol/L. Lipid-lowering agents such as fibrates and omega-3-fatty acids can be used to lower triglyceride levels in LPLD.
References
Familial Lipoprotein Lipase Deficiency References
[Metagen: FAMILIAL LIPOPROTEIN LIPASE DEFICIENCY](http://metagene.de/program/d.prg?id_d=325)
[OMIM: 238600](http://omim.org/entry/238600})
[Hyperlipidemia](http://en.wikipedia.org/wiki/Hyperlipidemia)
Burnett JR, Hooper AJ, Hegele RA: Familial Lipoprotein Lipase Deficiency
Pubmed: 20301485
Gadek KE, Wang H, Hall MN, Sungello M, Libby A, MacLaskey D, Eckel RH, Olwin BB: Striated muscle gene therapy for the treatment of lipoprotein lipase deficiency. PLoS One. 2018 Jan 5;13(1):e0190963. doi: 10.1371/journal.pone.0190963. eCollection 2018.
Pubmed: 29304082
Glycerolipid Metabolism References
Lehninger, A.L. Lehninger principles of biochemistry (4th ed.) (2005). New York: W.H Freeman.
Salway, J.G. Metabolism at a glance (3rd ed.) (2004). Alden, Mass.: Blackwell Pub.
Vance, D.E., and Vance, J.E. Biochemistry of lipids, lipoproteins, and membranes (4th ed.) (2002) Amsterdam; Boston: Elsevier.
Zhang P, Reue K: Lipin proteins and glycerolipid metabolism: Roles at the ER membrane and beyond. Biochim Biophys Acta Biomembr. 2017 Sep;1859(9 Pt B):1583-1595. doi: 10.1016/j.bbamem.2017.04.007. Epub 2017 Apr 11.
Pubmed: 28411173
Kiessling V, Crane JM, Tamm LK: Transbilayer effects of raft-like lipid domains in asymmetric planar bilayers measured by single molecule tracking. Biophys J. 2006 Nov 1;91(9):3313-26. doi: 10.1529/biophysj.106.091421. Epub 2006 Aug 11.
Pubmed: 16905614
Rusinol AE, Cui Z, Chen MH, Vance JE: A unique mitochondria-associated membrane fraction from rat liver has a high capacity for lipid synthesis and contains pre-Golgi secretory proteins including nascent lipoproteins. J Biol Chem. 1994 Nov 4;269(44):27494-502.
Pubmed: 7961664
Nagle CA, An J, Shiota M, Torres TP, Cline GW, Liu ZX, Wang S, Catlin RL, Shulman GI, Newgard CB, Coleman RA: Hepatic overexpression of glycerol-sn-3-phosphate acyltransferase 1 in rats causes insulin resistance. J Biol Chem. 2007 May 18;282(20):14807-15. doi: 10.1074/jbc.M611550200. Epub 2007 Mar 27.
Pubmed: 17389595
Helenius J, Ng DT, Marolda CL, Walter P, Valvano MA, Aebi M: Translocation of lipid-linked oligosaccharides across the ER membrane requires Rft1 protein. Nature. 2002 Jan 24;415(6870):447-50. doi: 10.1038/415447a.
Pubmed: 11807558
Alaimo C, Catrein I, Morf L, Marolda CL, Callewaert N, Valvano MA, Feldman MF, Aebi M: Two distinct but interchangeable mechanisms for flipping of lipid-linked oligosaccharides. EMBO J. 2006 Mar 8;25(5):967-76. doi: 10.1038/sj.emboj.7601024. Epub 2006 Feb 23.
Pubmed: 16498400
van Meer G, Voelker DR, Feigenson GW: Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol. 2008 Feb;9(2):112-24. doi: 10.1038/nrm2330.
Pubmed: 18216768
Baumann NA, Sullivan DP, Ohvo-Rekila H, Simonot C, Pottekat A, Klaassen Z, Beh CT, Menon AK: Transport of newly synthesized sterol to the sterol-enriched plasma membrane occurs via nonvesicular equilibration. Biochemistry. 2005 Apr 19;44(15):5816-26. doi: 10.1021/bi048296z.
Pubmed: 15823040
Sud M, Fahy E, Cotter D, Brown A, Dennis EA, Glass CK, Merrill AH Jr, Murphy RC, Raetz CR, Russell DW, Subramaniam S: LMSD: LIPID MAPS structure database. Nucleic Acids Res. 2007 Jan;35(Database issue):D527-32. doi: 10.1093/nar/gkl838. Epub 2006 Nov 10.
Pubmed: 17098933
Henry SA, Kohlwein SD, Carman GM: Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae. Genetics. 2012 Feb;190(2):317-49. doi: 10.1534/genetics.111.130286.
Pubmed: 22345606
Oelkers P, Cromley D, Padamsee M, Billheimer JT, Sturley SL: The DGA1 gene determines a second triglyceride synthetic pathway in yeast. J Biol Chem. 2002 Mar 15;277(11):8877-81. doi: 10.1074/jbc.M111646200. Epub 2001 Dec 18.
Pubmed: 11751875
Gaspar ML, Hofbauer HF, Kohlwein SD, Henry SA: Coordination of storage lipid synthesis and membrane biogenesis: evidence for cross-talk between triacylglycerol metabolism and phosphatidylinositol synthesis. J Biol Chem. 2011 Jan 21;286(3):1696-708. doi: 10.1074/jbc.M110.172296. Epub 2010 Oct 23.
Pubmed: 20972264
Gaspar ML, Aregullin MA, Jesch SA, Henry SA: Inositol induces a profound alteration in the pattern and rate of synthesis and turnover of membrane lipids in Saccharomyces cerevisiae. J Biol Chem. 2006 Aug 11;281(32):22773-85. doi: 10.1074/jbc.M603548200. Epub 2006 Jun 15.
Pubmed: 16777854
Gaspar ML, Jesch SA, Viswanatha R, Antosh AL, Brown WJ, Kohlwein SD, Henry SA: A block in endoplasmic reticulum-to-Golgi trafficking inhibits phospholipid synthesis and induces neutral lipid accumulation. J Biol Chem. 2008 Sep 12;283(37):25735-51. doi: 10.1074/jbc.M802685200. Epub 2008 Jul 9.
Pubmed: 18614533
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