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Pathway Description
Cardiolipin Biosynthesis
Saccharomyces cerevisiae
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2016-01-26
Last Updated: 2024-11-18
The biosynthesis of cardiolipin (CL) begins in the endoplasmic reticulum. Glycerone phosphate interacts with an NADPH resulting in the release of NADP and glycerol 3-phosphate. Glycerol 3-phosphate reacts with glycerol-3-phosphate O-acyltransferase resulting in the release of 1-acyl-sn-glycerol 3-phosphate (lysophosphatidic acid or LysoPA). The resulting compound reacts with an acyl-CoA via lysophosphatidate acyltransferase, resulting in the release of a phosphatidic acid (PA or 1,2-diacyl-sn-glycerol 3-phosphate). Phosphatidic acid is transported to the mitochondrial outer membrane. Once in, it gets transported into the mitochondrial inner membrane. The phosphatidic acid reacts with cytidine triphosphate through a phosphatidate cytidyltransferase resulting in the release of a CDP-diacylglycerol (CDP-DG). The resulting compound reacts with a glycerol 3-phosphate through a CDP-diacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase resulting in the release of cytidine monophosphate and phosphatidylglycerophosphate (PGP). PGP reacts with phosphatidylglycerophosphatase GEP4 resulting in the release of phosphatidylglycerol (PG). PG reacts with a CDP-DG through a cardiolipin synthase resulting in the release of CL and cytidine monophosphate. Cardiolipin remodelling begins with the removal of an acyl chain to form 1-monolysocardiolipin (1-MLCL) via the lipase Cld1p. This is followed by the enzyme Taz1p transferring an acyl chain from a phospholipid (e.g. phosphatidylcholine) to reform cardiolipin.
References
Cardiolipin Biosynthesis References
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Pubmed: 9024686
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Pubmed: 7941740
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Pubmed: 7731988
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Tettelin H, Agostoni Carbone ML, Albermann K, Albers M, Arroyo J, Backes U, Barreiros T, Bertani I, Bjourson AJ, Bruckner M, Bruschi CV, Carignani G, Castagnoli L, Cerdan E, Clemente ML, Coblenz A, Coglievina M, Coissac E, Defoor E, Del Bino S, Delius H, Delneri D, de Wergifosse P, Dujon B, Kleine K, et al.: The nucleotide sequence of Saccharomyces cerevisiae chromosome VII. Nature. 1997 May 29;387(6632 Suppl):81-4.
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Pubmed: 14562095
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Pubmed: 8091862
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Pubmed: 8196765
Albertyn J, Hohmann S, Thevelein JM, Prior BA: GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. Mol Cell Biol. 1994 Jun;14(6):4135-44. doi: 10.1128/mcb.14.6.4135.
Pubmed: 8196651
Wang HT, Rahaim P, Robbins P, Yocum RR: Cloning, sequence, and disruption of the Saccharomyces diastaticus DAR1 gene encoding a glycerol-3-phosphate dehydrogenase. J Bacteriol. 1994 Nov;176(22):7091-5. doi: 10.1128/jb.176.22.7091-7095.1994.
Pubmed: 7961476
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Pubmed: 15210723
Eriksson P, Andre L, Ansell R, Blomberg A, Adler L: Cloning and characterization of GPD2, a second gene encoding sn-glycerol 3-phosphate dehydrogenase (NAD+) in Saccharomyces cerevisiae, and its comparison with GPD1. Mol Microbiol. 1995 Jul;17(1):95-107. doi: 10.1111/j.1365-2958.1995.mmi_17010095.x.
Pubmed: 7476212
Mannhaupt G, Vetter I, Schwarzlose C, Mitzel S, Feldmann H: Analysis of a 26 kb region on the left arm of yeast chromosome XV. Yeast. 1996 Jan;12(1):67-76. doi: 10.1002/(SICI)1097-0061(199601)12:1%3C67::AID-YEA884%3E3.0.CO;2-F.
Pubmed: 8789261
Zheng Z, Zou J: The initial step of the glycerolipid pathway: identification of glycerol 3-phosphate/dihydroxyacetone phosphate dual substrate acyltransferases in Saccharomyces cerevisiae. J Biol Chem. 2001 Nov 9;276(45):41710-6. doi: 10.1074/jbc.M104749200. Epub 2001 Sep 5.
Pubmed: 11544256
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