PDH complex synthesizes acetyl-CoA from PYR

Pavlu-Pereira H, Silva MJ, Florindo C, Sequeira S, Ferreira AC, Duarte S, Rodrigues AL, Janeiro P, Oliveira A, Gomes D, Bandeira A, Martins E, Gomes R, Soares S, Tavares de Almeida I, Vicente JB, Rivera I. Pyruvate dehydrogenase complex deficiency: updating the clinical, metabolic and mutational landscapes in a cohort of Portuguese patients. Orphanet Journal of Rare Diseases. 2020 Oct 22;15(1):298. doi: 10.1186/s13023-020-01586-3.; Prasad C, Rupar T, Prasad AN. Pyruvate dehydrogenase deficiency and epilepsy. Brain Dev. 2011 Nov;33(10):856–65. doi: 10.1016/j.braindev.2011.08.003. PMID: 21908116.; Vijayakrishnan S, Kelly SM, Gilbert RJC, Callow P, Bhella D, Forsyth T, Lindsay JG, Byron O. Solution Structure and Characterisation of the Human Pyruvate Dehydrogenase Complex Core Assembly. Journal of Molecular Biology. 2010 May;399(1):71–93. doi: 10.1016/j.jmb.2010.03.043.; Head RA, Brown RM, Zolkipli Z, Shahdadpuri R, King MD, Clayton PT, Brown GK. Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency. Ann Neurol. 2005 Aug;58(2):234–41. doi: 10.1002/ana.20550. PMID: 16049940.; Brautigam CA, Chuang JL, Tomchick DR, Machius M, Chuang DT. Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations. J Mol Biol. 2005 Jul 15;350(3):543–52. doi: 10.1016/j.jmb.2005.05.014. PMID: 15946682.; Brown RM, Head RA, Boubriak II, Leonard JV, Thomas NH, Brown GK. Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency. Hum Genet. 2004 Jul;115(2):123–7. doi: 10.1007/s00439-004-1124-8. PMID: 15138885.; Hiromasa Y, Fujisawa T, Aso Y, Roche TE. Organization of the Cores of the Mammalian Pyruvate Dehydrogenase Complex Formed by E2 and E2 Plus the E3-binding Protein and Their Capacities to Bind the E1 and E3 Components. Journal of Biological Chemistry. 2004 Feb;279(8):6921–33. doi: 10.1074/jbc.m308172200.; Zhou ZH, McCarthy DB, O'Connor CM, Reed LJ, Stoops JK. The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes. Proc. Natl. Acad. Sci. U.S.A. 2001 Dec 18;98(26):14802–7. doi: 10.1073/pnas.011597698.; Lissens W, De Meirleir L, Seneca S, Liebaers I, Brown GK, Brown RM, Ito M, Naito E, Kuroda Y, Kerr DS, Wexler ID, Patel MS, Robinson BH, Seyda A. Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency. Hum Mutat. 2000;15(3):209–19. doi: 10.1002/(sici)1098-1004(200003)15:3<209::aid-humu1>3.0.co;2-k. PMID: 10679936.; Reed LJ, Hackert ML. Structure-function relationships in dihydrolipoamide acyltransferases. Journal of Biological Chemistry. 1990 Jun;265(16):8971–4. doi: 10.1016/s0021-9258(19)38795-2.

Metabolites

CO2

Formula: CO2 (43.98983)

CAS ID: 124-38-9

H+

Formula: H (1.0078246)

CAS ID: 12408-02-5

Magnesium cation

Formula: Mg (23.98505)

CAS ID: 22537-22-0

Potassium cation

Formula: K (38.963708)

CAS ID: 24203-36-9

pyruvate

Formula: C3H3O3 (87.00821880000001)

CAS ID: 57-60-3

NAD(1-)

Formula: C21H26N7O14P2 (662.1012936000001)

CAS ID: 53-84-9



Enzyme

EC Number name full name note
1.2.4.1 pyruvate dehydrogenase (acetyl-transferring) pyruvate:[dihydrolipoyllysine-residue acetyltransferase]-lipoyllysine 2-oxidoreductase (decarboxylating, acceptor-acetylating)
1.8.1.4 dihydrolipoyl dehydrogenase protein-N6-(dihydrolipoyl)lysine:NAD+ oxidoreductase
2.3.1.12 dihydrolipoyllysine-residue acetyltransferase acetyl-CoA:enzyme N6-(dihydrolipoyl)lysine S-acetyltransferase


Proteins

Protein ID name full name