2.02012-08-09 09:25:05 -06002015-06-03 17:21:36 -0600ECMDB21480M2MDB0018752,3-Dihydroxyisovaleric acid2,3-dihydroxyisovaleric acid (or 2,3-Dihydroxy-3-methylbutanoate) is invovled in branched chain amino acid biosynthesis. It is a substrate for Ketol-acid reductoisomerase (ilvC). This enzyme catalyzes the reaction: (R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH.2,3-Dihydroxy-3-methylbutanoate2,3-Dihydroxy-3-methylbutanoic acid2,3-Dihydroxy-isovalerate2,3-Dihydroxy-isovaleric acid2,3-Dihydroxyisovalerate2,3-DIVa,b-Dihydroxyisovaleratea,b-Dihydroxyisovaleric acidAlpha,beta-DihydroxyisovalerateAlpha,beta-Dihydroxyisovaleric acidα,β-Dihydroxyisovalerateα,β-Dihydroxyisovaleric acidC5H10O4134.1305134.0579088082,3-dihydroxy-3-methylbutanoic acid2,3-dihydroxyisovaleric acid1756-18-9CC(C)(O)C(O)C(O)=OInChI=1S/C5H10O4/c1-5(2,9)3(6)4(7)8/h3,6,9H,1-2H3,(H,7,8)JTEYKUFKXGDTEU-UHFFFAOYSA-NCytoplasmlogp-0.83logs0.60solubility5.29e+02 g/llogp-0.82pka_strongest_acidic3.8pka_strongest_basic-3.2iupac2,3-dihydroxy-3-methylbutanoic acidaverage_mass134.1305mono_mass134.057908808smilesCC(C)(O)C(O)C(O)=OformulaC5H10O4inchiInChI=1S/C5H10O4/c1-5(2,9)3(6)4(7)8/h3,6,9H,1-2H3,(H,7,8)inchikeyJTEYKUFKXGDTEU-UHFFFAOYSA-Npolar_surface_area77.76refractivity29.44polarizability12.47rotatable_bond_count2acceptor_count4donor_count3physiological_charge-1formal_charge0Valine, leucine and isoleucine biosynthesisec00290Pantothenate and CoA biosynthesisThe CoA biosynthesis requires compounds from two other pathways: aspartate metabolism and valine biosynthesis. It requires a Beta-Alanine and R-pantoate.
The compound (R)-pantoate is generated in two reactions, as shown by the interaction of alpha-ketoisovaleric acid, 5,10 methylene-THF and water through a 3-methyl-2-oxobutanoate hydroxymethyltransferase resulting in a tetrahydrofolic acid and a 2-dehydropantoate. This compound interacts with hydrogen through a NADPH driven acetohydroxy acid isomeroreductase resulting in the release of NADP and R-pantoate.
On the other hand L-aspartic acid interacts with a hydrogen ion and gets decarboxylated through an Aspartate 1- decarboxylase resulting in a carbon dioxide and a Beta-alanine.
Beta-alanine and R-pantoate interact with an ATP driven pantothenate synthetase resulting in pyrophosphate, AMP, hydrogen ion and pantothenic acid.
Pantothenic acid is phosphorylated through a ATP-driven pantothenate kinase resulting in a ADP, a hydrogen ion and D-4'-Phosphopantothenate. This compound interacts with a CTP and a L-cysteine resulting in a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a hydrogen ion, a pyrophosphate, a CMP and 4-phosphopantothenoylcysteine.
The latter compound interacts with a hydrogen ion through a fused 4'-phosphopantothenoylcysteine decarboxylase and phosphopantothenoylcysteine synthetase resulting in a carbon dioxide release and a 4-phosphopantetheine. This compound interacts with an ATP, hydrogen ion and an phosphopantetheine adenylyltransferase resulting in a release of pyrophosphate, and dephospho-CoA.
Dephospho-CoA reacts with an ATP driven dephospho-CoA kinase resulting in a ADP , a hydrogen ion and a Coenzyme A.
. The latter is converted into (R)-4'-phosphopantothenate is two steps, involving a β-alanine ligase and a kinase. In most organsims the ligase acts before the kinase (EC 6.3.2.1, pantoate—β-alanine ligase (AMP-forming) followed by EC 2.7.1.33, pantothenate kinase, as described in phosphopantothenate biosynthesis I and phosphopantothenate biosynthesis II. However, in archaea the order is reversed, and EC 2.7.1.169, pantoate kinase acts before EC 6.3.2.36, 4-phosphopantoate—β-alanine ligase, as described in phosphopantothenate biosynthesis III.
The kinases are feedback inhibited by CoA itself, accounting for the primary regulatory mechanism of CoA biosynthesis. The addition of L-cysteine to (R)-4'-phosphopantothenate, resulting in the formation of R-4'-phosphopantothenoyl-L-cysteine (PPC), is followed by decarboxylation of PPC to 4'-phosphopantetheine. The ultimate reaction is catalyzed by EC 2.7.1.24, dephospho-CoA kinase, which converts 4'-phosphopantetheine to CoA. All enzymes of this pathway are essential for growth.
The reactions in the biosynthetic route towards CoA are identical in most organisms, although there are differences in the functionality of the involved enzymes. In plants every step is catalyzed by single monofunctional enzymes, whereas in bacteria and mammals bifunctional enzymes are often employed [Rubio06].PW000828ec00770MetabolicMetabolic pathwayseco01100Specdb::CMs2346Specdb::NmrOneD289275Specdb::NmrOneD289276Specdb::NmrOneD289277Specdb::NmrOneD289278Specdb::NmrOneD289279Specdb::NmrOneD289280Specdb::NmrOneD289281Specdb::NmrOneD289282Specdb::NmrOneD289283Specdb::NmrOneD289284Specdb::NmrOneD289285Specdb::NmrOneD289286Specdb::NmrOneD289287Specdb::NmrOneD289288Specdb::NmrOneD289289Specdb::NmrOneD289290Specdb::NmrOneD289291Specdb::NmrOneD289292Specdb::NmrOneD289293Specdb::NmrOneD289294Specdb::MsMs23315Specdb::MsMs23316Specdb::MsMs23317Specdb::MsMs30113Specdb::MsMs30114Specdb::MsMs30115677657C0403915689Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948.18331064Yurtsever D. (2007). Fatty acid methyl ester profiling of Enterococcus and Esherichia coli for microbial source tracking. M.sc. Thesis. Villanova University: U.S.ADihydroxy-acid dehydrataseP05791ILVD_ECOLIilvDhttp://ecmdb.ca/proteins/P05791.xmlKetol-acid reductoisomeraseP05793ILVC_ECOLIilvChttp://ecmdb.ca/proteins/P05793.xml2,3-Dihydroxyisovaleric acid <> alpha-Ketoisovaleric acid + Water + a-Ketoisovaleric acidR012092-Acetolactate + NADPH + Hydrogen ion <> 2,3-Dihydroxyisovaleric acid + NADPR030512,3-Dihydroxyisovaleric acid > a-Ketoisovaleric acid + Water2,3-Dihydroxyisovaleric acid <>2 a-Ketoisovaleric acid + WaterPW_R005525