COASY explained

Bifunctional coenzyme A synthase is an enzyme that in mammals is encoded by the COASY gene that catalyses the synthesis of coenzyme A from 4'-phosphopantetheine.^{[1] [2] [3]}

Function

COASY is an enzyme that catalyzes the last two steps in the synthesis of coenzyme A from vitamin B₅ (pantothenic acid). The primary substrate is 4'-phosphopantetheine and COASY is a bifunctional enzyme in this pathway:

• 4′-Phosphopantetheine is adenylated to form dephospho-CoA by the enzyme phosphopantetheine adenylyl-transferase (PPAT; CoaD)
• Next, dephospho-CoA is phosphorylated to coenzyme A by the enzyme dephospho-CoA kinase (DPCK; CoaE)

In mammals this is a single enzyme, but in organisms including yeast and bacteria these enzymes are encoded by separate genes.^[4]

Interactions

COASY has been shown to interact with P70-S6 Kinase 1.^[5] In 2009, COASY has also been implicated in PI3K signaling, as it was shown to interact with a regulatory subunit of PI3K.^[6]

Clinical significance

Loss of function mutations to COASY have been associated with an ultra-rare disease that causes neurodegeneration with brain iron accumulation called COASY protein-associated neurodegeneration (CoPAN), or NBIA6.^{[7] [8]}

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Montagna M, Serova O, Sylla BS, Feunteun J, Lenoir GM . A 100-kb physical and transcriptional map around the EDH17B2 gene: identification of three novel genes and a pseudogene of a human homologue of the rat PRL-1 tyrosine phosphatase . Human Genetics . 96 . 5 . 532–538 . November 1995 . 8529999 . 10.1007/bf00197407 . 24567366 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Aghajanian S, Worrall DM . Identification and characterization of the gene encoding the human phosphopantetheine adenylyltransferase and dephospho-CoA kinase bifunctional enzyme (CoA synthase) . The Biochemical Journal . 365 . Pt 1 . 13–18 . July 2002 . 11994049 . 1222654 . 10.1042/BJ20020569 .
• Zhyvoloup A, Nemazanyy I, Panasyuk G, Valovka T, Fenton T, Rebholz H, Wang ML, Foxon R, Lyzogubov V, Usenko V, Kyyamova R, Gorbenko O, Matsuka G, Filonenko V, Gout IT . 6 . Subcellular localization and regulation of coenzyme A synthase . The Journal of Biological Chemistry . 278 . 50 . 50316–50321 . December 2003 . 14514684 . 10.1074/jbc.M307763200 . 13307789 . free .
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP . 6 . Large-scale characterization of HeLa cell nuclear phosphoproteins . Proceedings of the National Academy of Sciences of the United States of America . 101 . 33 . 12130–12135 . August 2004 . 15302935 . 514446 . 10.1073/pnas.0404720101 . free . 2004PNAS..10112130B .
• Nemazanyy I, Panasyuk G, Zhyvoloup A, Panayotou G, Gout IT, Filonenko V . Specific interaction between S6K1 and CoA synthase: a potential link between the mTOR/S6K pathway, CoA biosynthesis and energy metabolism . FEBS Letters . 578 . 3 . 357–362 . December 2004 . 15589845 . 10.1016/j.febslet.2004.10.091 . 9916948 . free .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–1178 . October 2005 . 16189514 . 10.1038/nature04209 . 4427026 . 2005Natur.437.1173R .
• Oh JH, Yang JO, Hahn Y, Kim MR, Byun SS, Jeon YJ, Kim JM, Song KS, Noh SM, Kim S, Yoo HS, Kim YS, Kim NS . 6 . Transcriptome analysis of human gastric cancer . Mammalian Genome . 16 . 12 . 942–954 . December 2005 . 16341674 . 10.1007/s00335-005-0075-2 . 69278 .
• Nemazanyy I, Panasyuk G, Breus O, Zhyvoloup A, Filonenko V, Gout IT . Identification of a novel CoA synthase isoform, which is primarily expressed in the brain . Biochemical and Biophysical Research Communications . 341 . 4 . 995–1000 . March 2006 . 16460672 . 10.1016/j.bbrc.2006.01.051 .

Notes and References

1. Daugherty M, Polanuyer B, Farrell M, Scholle M, Lykidis A, de Crécy-Lagard V, Osterman A . Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics . The Journal of Biological Chemistry . 277 . 24 . 21431–21439 . June 2002 . 11923312 . 10.1074/jbc.M201708200 . free .
2. Zhyvoloup A, Nemazanyy I, Babich A, Panasyuk G, Pobigailo N, Vudmaska M, Naidenov V, Kukharenko O, Palchevskii S, Savinska L, Ovcharenko G, Verdier F, Valovka T, Fenton T, Rebholz H, Wang ML, Shepherd P, Matsuka G, Filonenko V, Gout IT . 6 . Molecular cloning of CoA Synthase. The missing link in CoA biosynthesis . The Journal of Biological Chemistry . 277 . 25 . 22107–22110 . June 2002 . 11980892 . 10.1074/jbc.C200195200 . free .
3. Web site: Entrez Gene: COASY Coenzyme A synthase.
4. Evers C, Seitz A, Assmann B, Opladen T, Karch S, Hinderhofer K, Granzow M, Paramasivam N, Eils R, Diessl N, Bartram CR, Moog U . 6 . Diagnosis of CoPAN by whole exome sequencing: Waking up a sleeping tiger's eye . American Journal of Medical Genetics. Part A . 173 . 7 . 1878–1886 . July 2017 . 28489334 . 10.1002/ajmg.a.38252 . 27153945 .
5. Nemazanyy I, Panasyuk G, Zhyvoloup A, Panayotou G, Gout IT, Filonenko V . Specific interaction between S6K1 and CoA synthase: a potential link between the mTOR/S6K pathway, CoA biosynthesis and energy metabolism . FEBS Letters . 578 . 3 . 357–362 . December 2004 . 15589845 . 10.1016/j.febslet.2004.10.091 . 9916948 . free .
6. Breus O, Panasyuk G, Gout IT, Filonenko V, Nemazanyy I . CoA synthase is in complex with p85alphaPI3K and affects PI3K signaling pathway . Biochemical and Biophysical Research Communications . 385 . 4 . 581–585 . August 2009 . 19482007 . 10.1016/j.bbrc.2009.05.102 .
7. van Dijk T, Ferdinandusse S, Ruiter JP, Alders M, Mathijssen IB, Parboosingh JS, Innes AM, Meijers-Heijboer H, Poll-The BT, Bernier FP, Wanders RJ, Lamont RE, Baas F . 6 . Biallelic loss of function variants in COASY cause prenatal onset pontocerebellar hypoplasia, microcephaly, and arthrogryposis . European Journal of Human Genetics . 26 . 12 . 1752–1758 . December 2018 . 30089828 . 10.1038/s41431-018-0233-0 . 6244412 .
8. Web site: OMIM Entry - #615643 - NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 6; NBIA6 . www.omim.org . 21 April 2022 . en-us.