Chemistry:Fumarylacetoacetic acid
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| Preferred IUPAC name
(2E)-4,6-Dioxooct-2-enedioic acid | |
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3D model (JSmol)
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| ChemSpider | |
| MeSH | Fumarylacetoacetate |
PubChem CID
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| Properties | |
| C8H8O6 | |
| Molar mass | 200.146 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). | |
| Infobox references | |
Fumarylacetoacetic acid (fumarylacetoacetate) is an intermediate in the metabolism of tyrosine. It is formed through the conversion of 4-maleylacetoacetic acid into fumarylacetoacetic acid by the enzyme maleylacetoacetate isomerase. Fumarylacetoacetic acid is hydrolyzed by the enzyme fumarylacetoacetate hydrolase (FAH), producing acetoacetate and fumarate.[1] These compounds may then enter various other metabolic pathways.
Biosynthesis
The amino acid tyrosine is metabolised in a series of reactions, one of which is catalysed by homogentisate 1,2-dioxygenase. This converts the intermediate homogentisic acid into 4-maleylacetoacetic acid.[2][3]
The enzyme maleylacetoacetate isomerase subsequently converts 4-maleylacetoacetic acid to its geometric isomer, fumarylacetoacetic acid.[4]
- REDIRECT Template:Chemical reaction
Metabolism
The enzyme fumarylacetoacetate hydrolase (FAH) cleaves fumarylacetoacetic acid at its carbon-carbon bond during a hydrolysis reaction.[5] This is the final step in phenylalanine and tyrosine metabolism, yielding fumaric acid and acetoacetic acid. These hydrolytic reactions are essential during aromatic amino acid metabolism in humans.[6]
- REDIRECT Template:Chemical reaction
Clinical significance
Fumarylacetoacetate may accumulate in patients with Tyrosinemia type I, in which there is a deficiency of the FAH enzyme.[7] In this disease, fumarylacetoacetate and precursors in the catabolism of tyrosine, including maleylacetoacetic acid, succinylacetone, and homogentisic acid.
References
- ↑ Bateman, Raynard L.; Bhanumoorthy, P.; Witte, John F.; McClard, Ronald W.; Grompe, Markus; Timm, David E. (2001-01-01). "Mechanistic Inferences from the Crystal Structure of Fumarylacetoacetate Hydrolase with a Bound Phosphorus-based Inhibitor *" (in English). Journal of Biological Chemistry 276 (18): 15284–15291. doi:10.1074/jbc.M007621200. ISSN 0021-9258. PMID 11154690.
- ↑ Borowski, Tomasz; Georgiev, Valentin; Siegbahn, Per E. M. (2005). "Catalytic Reaction Mechanism of Homogentisate Dioxygenase: A Hybrid DFT Study". Journal of the American Chemical Society 127 (49): 17303–17314. doi:10.1021/ja054433j. PMID 16332080.
- ↑ Timm, David E.; Titus, Greg P.; Mueller, Heather A.; Burgner, John; Rodríguez De Córdoba, Santiago; Peñalva, Miguel A. (2000). "Crystal structure of human homogentisate dioxygenase". Nature Structural Biology 7 (7): 542–546. doi:10.1038/76756. PMID 10876237.
- ↑ Polekhina, Galina; Board, Philip G.; Blackburn, Anneke C.; Parker, Michael W. (2001). "Crystal Structure of Maleylacetoacetate Isomerase/Glutathione Transferase Zeta Reveals the Molecular Basis for Its Remarkable Catalytic Promiscuity". Biochemistry 40 (6): 1567–1576. doi:10.1021/bi002249z. PMID 11327815.
- ↑ "Crystal structure and mechanism of a carbon-carbon bond hydrolase". Structure 7 (9): 1023–1033. September 1999. doi:10.1016/s0969-2126(99)80170-1. PMID 10508789.
- ↑ Universal protein resource accession number P16930 for "FAH - Fumarylacetoacetase - Homo sapiens (Human) - FAH gene & protein" at UniProt.
- ↑ Chakrapani, Anupam; Holme, Elisabeth (2006). "Disorders of Tyrosine Metabolism". in Fernandes, John; Saudubray, Jean-Marie; van den Berghe, Georges et al. (in en). Inborn Metabolic Diseases. Springer. pp. 233–243. doi:10.1007/978-3-540-28785-8_18. ISBN 978-3-540-28785-8. http://www.bmj.com/cgi/content/short/3/5617/511-a.
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