BioPAX pathway converted from "lipo-PDH decarboxylates PYR to Ac-CoA" in the Reactome database.
lipo-PDH decarboxylates PYR to Ac-CoA
lipo-PDH decarboxylates PYR to Ac-CoA
pyruvate + CoASH + NAD+ => acetylCoA + CO2 + NADH + H+
Oxidative decarboxylation of pyruvate to acetyl CoA by pyruvate dehydrogenase
线粒体丙酮酸德hydrogenase complex catalyzes the reaction of pyruvate, CoASH, and NAD+ to form acetylCoA, CO2, and NADH. The enzyme complex contains multiple copies of three different proteins, E1 alpha, E1 beta, E2, and E3, each with distinct catalytic activities (Reed and Hackert 1990; Zhou et al 2001). The reaction starts with the oxidative decarboxylation of pyruvate catalyzed by E1 alpha and beta (pyruvate dehydrogenase). Lipoamide cofactor associated with E1 is reduced at the same time. Next, the acetyl group derived from pyruvate is transferred to coenzyme A in two steps catalyzed by E2 (dihydrolipolyl transacetylase). Finally, the oxidized form of lipoamide is regenerated and electrons are transferred to NAD+ in two steps catalyzed by E3 (dihydrolipoyl dehydrogenase). The biochemical details of this reaction have been worked out with pyruvate dehydrogenase complex and subunits purified from bovine tissue and other non-human sources. Direct evidence for the roles of the corresponding human proteins comes from studies of patients expressing mutant forms of E1 alpha (Lissens et al. 2000), E1 beta (Brown et al. 2004), E2 (Head et al. 2005), and E3 (Brautigam et al. 2005).
Authored: Birney, E, Schmidt, EE, 2003-01-28 00:00:00
Edited: D'Eustachio, P, 0000-00-00 00:00:00
Reactome DB_ID: 113557
1
mitochondrial matrix
GO
0005759
pyruvate [ChEBI:15361]
pyruvate
2-oxopropanoate
2-oxopropanoic acid, ion(1-)
Reactome
//www.joaskin.com
ChEBI
15361
Reactome DB_ID: 113526
1
NAD(1-) [ChEBI:57540]
NAD(1-)
NAD(+)
adenosine 5'-{3-[1-(3-carbamoylpyridinio)-1,4-anhydro-D-ribitol-5-yl] diphosphate}
NAD anion
ChEBI
57540
Reactome DB_ID: 29374
1
coenzyme A [ChEBI:15346]
coenzyme A
ChEBI
15346
Reactome DB_ID: 113559
1
acetyl-CoA [ChEBI:15351]
acetyl-CoA
ChEBI
15351
Reactome DB_ID: 29362
1
NADH(2-) [ChEBI:57945]
NADH(2-)
NADH dianion
adenosine 5'-{3-[1-(3-carbamoyl-1,4-dihydropyridin-1-yl)-1,4-anhydro-D-ribitol-5-yl] diphosphate}
NADH
ChEBI
57945
Reactome DB_ID: 29376
1
carbon dioxide [ChEBI:16526]
carbon dioxide
ChEBI
16526
PHYSIOL-LEFT-TO-RIGHT
ACTIVATION
Reactome DB_ID: 70070
lipo-PDH [mitochondrial matrix]
lipo-PDH
pyruvate dehydrogenase complex
Reactome DB_ID: 70059
12
UniProt:O00330 PDHX
PDHX
PDHX
PDX1
FUNCTION Required for anchoring dihydrolipoamide dehydrogenase (E3) to the dihydrolipoamide transacetylase (E2) core of the pyruvate dehydrogenase complexes of eukaryotes. This specific binding is essential for a functional PDH complex.SUBUNIT Part of the inner core of the multimeric pyruvate dehydrogenase complex that is composed of about 48 DLAT and 12 PDHX molecules (PubMed:14638692, PubMed:20361979). This core binds multiple copies of pyruvate dehydrogenase (subunits PDH1A and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (PubMed:14638692). Interacts with SIRT4 (PubMed:25525879). Interacts with DLD (PubMed:20385101, PubMed:16263718, PubMed:16442803, PubMed:20160912, PubMed:20361979).PTM Delipoylated at Lys-97 by SIRT4, delipoylation decreases the PHD complex activity.SIMILARITY Belongs to the 2-oxoacid dehydrogenase family.
Homo sapiens
NCBI Taxonomy
9606
UniProt
O00330
Chain Coordinates
54
EQUAL
501
EQUAL
Reactome DB_ID: 69971
20
lipo-K-132,K259-DLAT trimer [mitochondrial matrix]
lipo-K-132,K259-DLAT trimer
pyruvate dehydrogenase E2 trimer
Reactome DB_ID: 69969
3
UniProt:P10515 DLAT
DLAT
DLTA
DLAT
FUNCTION The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.SUBUNIT Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (subunits PDH1A and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (PubMed:14638692). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (PubMed:14638692, PubMed:20361979). Interacts with PDK2 and PDK3 (PubMed:15861126, PubMed:17532006, PubMed:17683942, PubMed:18387944). Interacts with SIRT4 (PubMed:25525879). Interacts with PDHB (PubMed:20160912).PTM Delipoylated at Lys-132 and Lys-259 by SIRT4, delipoylation decreases the PHD complex activity.DISEASE Primary biliary cirrhosis is a chronic, progressive cholestatic liver disease characterized by the presence of antimitochondrial autoantibodies in patients' serum. It manifests with inflammatory obliteration of intra-hepatic bile duct, leading to liver cell damage and cirrhosis. Patients with primary biliary cirrhosis show autoantibodies against the E2 component of pyruvate dehydrogenase complex.SIMILARITY Belongs to the 2-oxoacid dehydrogenase family.
UniProt
P10515
N6-lipoyl-L-lysine at 132
132
EQUAL
N6-lipoyl-L-lysine [MOD:00127]
N6-lipoyl-L-lysine at 259
259
EQUAL
87
EQUAL
647
EQUAL
Reactome Database ID Release 77
69971
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=69971
Reactome
R-HSA-69971
2
Reactome稳定的标识符。Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-69971.2
Reactome DB_ID: 69980
6
aKADH E3 dimer [mitochondrial matrix]
aKADH E3 dimer
alpha-keto acid dehydrogenase E3 homodimer
Reactome DB_ID: 69979
2
aKADH E3 [mitochondrial matrix]
aKADH E3
alpha-keto acid dehydrogenase E3 holoenzyme
DLD:FAD
Reactome DB_ID: 113596
1
FAD [ChEBI:16238]
FAD
Flavin adenine dinucleotide
ChEBI
16238
Reactome DB_ID: 69978
1
UniProt:P09622 DLD
DLD
PHE3
GCSL
DLD
LAD
FUNCTION Lipoamide dehydrogenase is a component of the glycine cleavage system as well as an E3 component of three alpha-ketoacid dehydrogenase complexes (pyruvate-, alpha-ketoglutarate-, and branched-chain amino acid-dehydrogenase complex) (PubMed:15712224, PubMed:16442803, PubMed:16770810, PubMed:17404228, PubMed:20160912, PubMed:20385101). The 2-oxoglutarate dehydrogenase complex is mainly active in the mitochondrion (PubMed:29211711). A fraction of the 2-oxoglutarate dehydrogenase complex also localizes in the nucleus and is required for lysine succinylation of histones: associates with KAT2A on chromatin and provides succinyl-CoA to histone succinyltransferase KAT2A (PubMed:29211711). In monomeric form may have additional moonlighting function as serine protease (PubMed:17404228). Involved in the hyperactivation of spermatazoa during capacitation and in the spermatazoal acrosome reaction (By similarity).ACTIVITY REGULATION Disruption of native heterodimer state inhibits primary dihydrolipoamide dehydrogenase activity and induces serine protease activity.SUBUNIT Homodimer (PubMed:15946682). Part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (subunits PDHA (PDHA1 or PDHA2) and PDHB, E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (PubMed:14638692). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (by non covalent bonds) (PubMed:14638692, PubMed:20361979). The 2-oxoglutarate dehydrogenase complex is composed of OGDH (2-oxoglutarate dehydrogenase; E1), DLST (dihydrolipoamide succinyltransferase; E2) and DLD (dihydrolipoamide dehydrogenase; E3). It contains multiple copies of the three enzymatic components (E1, E2 and E3). In the nucleus, the 2-oxoglutarate dehydrogenase complex associates with KAT2A (PubMed:29211711). Interacts with PDHX (PubMed:20385101, PubMed:16442803, PubMed:20160912, PubMed:20361979).PTM Tyrosine phosphorylated.MISCELLANEOUS The active site is a redox-active disulfide bond.SIMILARITY Belongs to the class-I pyridine nucleotide-disulfide oxidoreductase family.
UniProt
P09622
36
EQUAL
509
EQUAL
Reactome Database ID Release 77
69979
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=69979
Reactome
R-HSA-69979
2
Reactome稳定的标识符。Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-69979.2
Reactome Database ID Release 77
69980
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=69980
Reactome
R-HSA-69980
2
Reactome稳定的标识符。Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-69980.2
Reactome DB_ID: 69968
22
PDH E1 [mitochondrial matrix]
PDH E1
pyruvate dehydrogenase E1 complex
Reactome DB_ID: 113547
2
thiamine(1+) diphosphate(3-) [ChEBI:58937]
thiamine(1+) diphosphate(3-)
thiamine diphosphate
thiamine diphosphate dianion
thiamine diphosphate(2-)
ChEBI
58937
Reactome DB_ID: 69967
2
UniProt:P11177 PDHB
PDHB
PHE1B
PDHB
FUNCTION The pyruvate dehydrogenase complex catalyzes the overall conversion of pyruvate to acetyl-CoA and CO(2), and thereby links the glycolytic pathway to the tricarboxylic cycle.SUBUNIT Heterotetramer of two PDHA1 and two PDHB subunits (PubMed:12651851, PubMed:17474719, PubMed:19081061). The heterotetramer interacts with DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3) (PubMed:14638692). These subunits are bound to an inner core composed of about 48 DLAT and 12 PDHX molecules (PubMed:14638692). Interacts with DLAT (PubMed:20160912).
UniProt
P11177
31
EQUAL
359
EQUAL
Converted from EntitySet in Reactome
Reactome DB_ID: 8953511
2
PDHA1,2 [mitochondrial matrix]
从Reactome EntitySet转换。每个同义词is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity
PDHA2 [mitochondrial matrix]
PDHA1 [mitochondrial matrix]
UniProt
P29803
UniProt
P08559
Reactome Database ID Release 77
69968
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=69968
Reactome
R-HSA-69968
3
Reactome稳定的标识符。Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-69968.3
Reactome Database ID Release 77
70070
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=70070
Reactome
R-HSA-70070
8
Reactome稳定的标识符。Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-70070.8
GO
0004738
GO molecular function
Reactome Database ID Release 77
450854
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=450854
Reactome Database ID Release 77
71397
Database identifier. Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=71397
Reactome
R-HSA-71397
2
Reactome稳定的标识符。Use this URL to connect to the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-71397.2
16049940
Pubmed
2005
Clinical and genetic spectrum of pyruvate dehydrogenase deficiency: dihydrolipoamide acetyltransferase (E2) deficiency
Head, RA
Brown, RM
Zolkipli Z
Shahdadpuri, R
King, MD
Clayton, Peter T
Brown, GK
Ann Neurol 58:234-41
10679936
Pubmed
2000
Mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1) in patients with a pyruvate dehydrogenase complex deficiency
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
Hum Mutat 15:209-19
2188967
Pubmed
1990
Structure-function relationships in dihydrolipoamide acyltransferases.
Reed, LJ
Hackert, ML
J Biol Chem 265:8971-4
11752427
Pubmed
2001
The remarkable structural and functional organization of the eukaryotic pyruvate dehydrogenase complexes.
Zhou, ZH
McCarthy, DB
O'Connor, CM
Reed, LJ
Stoops, JK
Proc Natl Acad Sci U S A 98:14802-7
15138885
Pubmed
2004
Mutations in the gene for the E1beta subunit: a novel cause of pyruvate dehydrogenase deficiency
Brown, RM
Head, RA
Boubriak, II
Leonard, JV
Thomas, NH
Brown, GK
Hum Genet 115:123-7
15946682
Pubmed
2005
Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations
布劳提根,
Chuang, JL
Tomchick, DR
Machius, M
Chuang, DT
J Mol Biol 350:543-52