2.02012-10-10 12:22:28 -06002015-09-13 15:15:34 -0600ECMDB23216M2MDB003606pantotheine 4'-phosphateA phosphopantetheine that has formula C11H23N2O7PSPantetheine 4'-phosphatePantetheine 4'-phosphoric acidPantotheine 4'-phosphoric acidPantotheine-4'-phosphatePantotheine-4'-phosphoric acidPhosphopantetheinePhosphopantotheineC11H23N2O7PS358.348358.096358302[3-hydroxy-2,2-dimethyl-3-({2-[(2-sulfanylethyl)carbamoyl]ethyl}carbamoyl)propoxy]phosphonic acidpantetheine 4'-phosphate2226-71-3CC(C)(COP(O)(O)=O)C(O)C(=O)NCCC(=O)NCCSInChI=1S/C11H23N2O7PS/c1-11(2,7-20-21(17,18)19)9(15)10(16)13-4-3-8(14)12-5-6-22/h9,15,22H,3-7H2,1-2H3,(H,12,14)(H,13,16)(H2,17,18,19)JDMUPRLRUUMCTL-UHFFFAOYSA-NSolidCytoplasm (Predicted from LogP)logp-0.71logs-2.98solubility3.75e-01 g/llogp-1.7pka_strongest_acidic1.79pka_strongest_basic-1.5iupac[3-hydroxy-2,2-dimethyl-3-({2-[(2-sulfanylethyl)carbamoyl]ethyl}carbamoyl)propoxy]phosphonic acidaverage_mass358.348mono_mass358.096358302smilesCC(C)(COP(O)(O)=O)C(O)C(=O)NCCC(=O)NCCSformulaC11H23N2O7PSinchiInChI=1S/C11H23N2O7PS/c1-11(2,7-20-21(17,18)19)9(15)10(16)13-4-3-8(14)12-5-6-22/h9,15,22H,3-7H2,1-2H3,(H,12,14)(H,13,16)(H2,17,18,19)inchikeyJDMUPRLRUUMCTL-UHFFFAOYSA-Npolar_surface_area145.19refractivity81.58polarizability34.28rotatable_bond_count10acceptor_count6donor_count6physiological_charge-2formal_charge0Pantothenate 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::CMs2894Specdb::CMs38063Specdb::NmrOneD315401Specdb::NmrOneD315402Specdb::NmrOneD315403Specdb::NmrOneD315404Specdb::NmrOneD315405Specdb::NmrOneD315406Specdb::NmrOneD315407Specdb::NmrOneD315408Specdb::NmrOneD315409Specdb::NmrOneD315410Specdb::NmrOneD315411Specdb::NmrOneD315412Specdb::NmrOneD315413Specdb::NmrOneD315414Specdb::NmrOneD315415Specdb::NmrOneD315416Specdb::NmrOneD315417Specdb::NmrOneD315418Specdb::NmrOneD315419Specdb::NmrOneD315420Specdb::MsMs27113Specdb::MsMs27114Specdb::MsMs27115Specdb::MsMs33671Specdb::MsMs33672Specdb::MsMs33673HMDB01416987C0113416858PANTETHEINE-PFDB022609Tahiliani AG, Beinlich CJ: Pantothenic acid in health and disease. Vitam Horm. 1991;46:165-228.1746161Masuda, Toru; Fujii, Shoichiro; Takanohashi, Kunio. Pantetheine 4'-phosphate. Jpn. Tokkyo Koho (1971), 3 pp.Phosphopantetheine adenylyltransferaseP0A6I6COAD_ECOLIcoaDhttp://ecmdb.ca/proteins/P0A6I6.xmlDephospho-CoA kinaseP0A6I9COAE_ECOLIcoaEhttp://ecmdb.ca/proteins/P0A6I9.xmlCoenzyme A biosynthesis bifunctional protein coaBCP0ABQ0COABC_ECOLIcoaBChttp://ecmdb.ca/proteins/P0ABQ0.xml4-Phosphopantothenoylcysteine > pantotheine 4'-phosphate + Carbon dioxideAdenosine triphosphate + pantotheine 4'-phosphate > Pyrophosphate + 3'-dephospho-CoA4-Phosphopantothenoylcysteine + Hydrogen ion <> Carbon dioxide + Pantetheine 4'-phosphate + pantotheine 4'-phosphateR03269P-PANTOCYSDECARB-RXNPantetheine + Adenosine triphosphate + Pantetheine > Pantetheine 4'-phosphate + Adenosine diphosphate + pantotheine 4'-phosphate + ADPPW_R0029924-Phosphopantothenoylcysteine > Pantetheine 4'-phosphate + Carbon dioxide + pantotheine 4'-phosphatePW_R002993Pantetheine 4'-phosphate + Adenosine triphosphate + pantotheine 4'-phosphate > Dephospho-CoA + PyrophosphatePW_R002995Dephospho-CoA + Water <> Pantetheine 4'-phosphate + Adenosine monophosphate + pantotheine 4'-phosphatePW_R002997