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Pathway Description
Cardiolipin Biosynthesis CL(14:0/21:0/a-25:0/a-25:0)
Mus musculus
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2024-06-15
Last Updated: 2024-06-15
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. It requires a divalent metal cation cofactor.
References
Cardiolipin Biosynthesis CL(14:0/21:0/a-25:0/a-25:0) References
Dobson DE, Groves DL, Spiegelman BM: Nucleotide sequence and hormonal regulation of mouse glycerophosphate dehydrogenase mRNA during adipocyte and muscle cell differentiation. J Biol Chem. 1987 Feb 5;262(4):1804-9.
Pubmed: 3027100
Ireland RC, Kotarski MA, Johnston LA, Stadler U, Birkenmeier E, Kozak LP: Primary structure of the mouse glycerol-3-phosphate dehydrogenase gene. J Biol Chem. 1986 Sep 5;261(25):11779-85.
Pubmed: 3755721
Phillips M, Djian P, Green H: The nucleotide sequence of three genes participating in the adipose differentiation of 3T3 cells. J Biol Chem. 1986 Aug 15;261(23):10821-7.
Pubmed: 3015943
Shin DH, Paulauskis JD, Moustaid N, Sul HS: Transcriptional regulation of p90 with sequence homology to Escherichia coli glycerol-3-phosphate acyltransferase. J Biol Chem. 1991 Dec 15;266(35):23834-9.
Pubmed: 1721057
Clee SM, Yandell BS, Schueler KM, Rabaglia ME, Richards OC, Raines SM, Kabara EA, Klass DM, Mui ET, Stapleton DS, Gray-Keller MP, Young MB, Stoehr JP, Lan H, Boronenkov I, Raess PW, Flowers MT, Attie AD: Positional cloning of Sorcs1, a type 2 diabetes quantitative trait locus. Nat Genet. 2006 Jun;38(6):688-93. doi: 10.1038/ng1796. Epub 2006 May 7.
Pubmed: 16682971
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Pubmed: 16141072
This pathway was propagated using PathWhiz -
Pon, A. et al. Pathways with PathWhiz (2015) Nucleic Acids Res. 43(Web Server issue): W552–W559.
Propagated from SMP0202468
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