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Pathway Description
Cardiolipin Biosynthesis CL(16:0/18:0/18:3(6Z,9Z,12Z)/20:4(5Z,8Z,11Z,14Z))
Caenorhabditis elegans
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2018-08-07
Last Updated: 2019-11-27
Cardiolipin (CL) is an important component of the inner mitochondrial membrane where it constitutes about 20% of the total lipid composition. It is essential for the optimal function of numerous enzymes that are involved in mitochondrial energy metabolism (Wikipedia). Cardiolipin biosynthesis occurs mainly in the mitochondria, but there also exists an alternative synthesis route for CDP-diacylglycerol that takes place in the endoplasmic reticulum. This second route may supplement this pathway. All membrane-localized enzymes are coloured dark green in the image. First, dihydroxyacetone phosphate (or glycerone phosphate) from glycolysis is used by the cytosolic enzyme glycerol-3-phosphate dehydrogenase [NAD(+)] to synthesize sn-glycerol 3-phosphate. Second, the mitochondrial outer membrane enzyme glycerol-3-phosphate acyltransferase esterifies an acyl-group to the sn-1 position of sn-glycerol 3-phosphate to form 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LPA). Third, the enzyme 1-acyl-sn-glycerol-3-phosphate acyltransferase converts LPA into phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate) by esterifying an acyl-group to the sn-2 position of the glycerol backbone. PA is then transferred to the inner mitochondrial membrane to continue cardiolipin synthesis. Fourth, magnesium-dependent phosphatidate cytidylyltransferase catalyzes the conversion of PA into CDP-diacylglycerol. Fifth, CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase synthesizes phosphatidylglycerophosphate (PGP). Sixth, phosphatidylglycerophosphatase and protein-tyrosine phosphatase dephosphorylates PGP to form phosphatidylglycerol (PG). Last, cardiolipin synthase catalyzes the synthesis of cardiolipin by transferring a phosphatidyl group from a second CDP-diacylglycerol to PG.
References
Cardiolipin Biosynthesis CL(16:0/18:0/18:3(6Z,9Z,12Z)/20:4(5Z,8Z,11Z,14Z)) References
Tian HF, Feng JM, Wen JF: The evolution of cardiolipin biosynthesis and maturation pathways and its implications for the evolution of eukaryotes. BMC Evol Biol. 2012 Mar 13;12:32. doi: 10.1186/1471-2148-12-32.
Pubmed: 22409430
Watts JL, Ristow M: Lipid and Carbohydrate Metabolism in Caenorhabditis elegans. Genetics. 2017 Oct;207(2):413-446. doi: 10.1534/genetics.117.300106.
Pubmed: 28978773
Vrablik TL, Petyuk VA, Larson EM, Smith RD, Watts JL: Lipidomic and proteomic analysis of Caenorhabditis elegans lipid droplets and identification of ACS-4 as a lipid droplet-associated protein. Biochim Biophys Acta. 2015 Oct;1851(10):1337-45. doi: 10.1016/j.bbalip.2015.06.004. Epub 2015 Jun 27.
Pubmed: 26121959
Wilson R, Ainscough R, Anderson K, Baynes C, Berks M, Bonfield J, Burton J, Connell M, Copsey T, Cooper J, et al.: 2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans. Nature. 1994 Mar 3;368(6466):32-8. doi: 10.1038/368032a0.
Pubmed: 7906398
Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012-8. doi: 10.1126/science.282.5396.2012.
Pubmed: 9851916
Bahmanyar S, Biggs R, Schuh AL, Desai A, Muller-Reichert T, Audhya A, Dixon JE, Oegema K: Spatial control of phospholipid flux restricts endoplasmic reticulum sheet formation to allow nuclear envelope breakdown. Genes Dev. 2014 Jan 15;28(2):121-6. doi: 10.1101/gad.230599.113.
Pubmed: 24449268
This pathway was generated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Generated from SMP0082506
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