Threonine catabolism (Homo sapiens)

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2, 61-42, 5mitochondrial matrixmitochondrial intermembrane spaceGlyNAD+TDH GCAT:PXLP dimer:TDHtetramerAc-CoAATPL-ThrGCAT NADH2A-3OBUPPiH+CoA-SHPXLP


Description

The degradation of L-threonine to glycine in both prokaryotes and eukaryotes takes place through a two-step biochemical pathway in mitochondria (Dale 1978). In the first step, L-threonine is oxidised to 2-amino-3-oxobutanoate. This reaction is catalysed by mitochondrial L-threonine 3-dehydrogenase tetramer (TDH tetramer). In the second step, mitochondrial 2-amino-3-ketobutyrate coenzyme A ligase (GCAT, aka KBL) catalyses the reaction between 2-amino-3-oxobutanoate and coenzyme A to form glycine and acetyl-CoA. GCAT resides on the mitochondrial inner membrane in dimeric form and requires pyridoxal 5-phosphate (PXLP) as cofactor. GCAT is thought to exist on the mitochondrial inner membrane in complex with TDH. With these two enzymes located together, it stops the rapid and spontaneous decarboxylation of 2A-3OBU to aminoacetone and carbon dioxide and instead, results in glycine formation (Tressel et al. 1986). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8849175
Reactome-version 
Reactome version: 61
Reactome Author 
Reactome Author: Jassal, Bijay

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Bibliography

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History

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CompareRevisionActionTimeUserComment
115075view17:02, 25 January 2021ReactomeTeamReactome version 75
113517view11:59, 2 November 2020ReactomeTeamReactome version 74
112715view16:11, 9 October 2020ReactomeTeamReactome version 73
101631view11:49, 1 November 2018ReactomeTeamreactome version 66
101167view21:36, 31 October 2018ReactomeTeamreactome version 65
100693view20:09, 31 October 2018ReactomeTeamreactome version 64
100243view16:54, 31 October 2018ReactomeTeamreactome version 63
99795view15:19, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99345view12:48, 31 October 2018ReactomeTeamreactome version 62
93805view13:37, 16 August 2017ReactomeTeamreactome version 61
93346view11:21, 9 August 2017ReactomeTeamreactome version 61
88405view11:39, 5 August 2016FehrhartOntology Term : 'threonine degradation pathway' added !
86430view09:18, 11 July 2016ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
2A-3OBUMetaboliteCHEBI:16944 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Ac-CoAMetaboliteCHEBI:15351 (ChEBI)
CoA-SHMetaboliteCHEBI:15346 (ChEBI)
GCAT ProteinO75600 (Uniprot-TrEMBL)
GCAT:PXLP dimer:TDH tetramerComplexR-HSA-6798680 (Reactome)
GlyMetaboliteCHEBI:57305 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
L-ThrMetaboliteCHEBI:57926 (ChEBI)
NAD+MetaboliteCHEBI:15846 (ChEBI)
NADHMetaboliteCHEBI:16908 (ChEBI)
PPiMetaboliteCHEBI:29888 (ChEBI)
PXLP MetaboliteCHEBI:18405 (ChEBI)
TDH ProteinQ8IZJ6 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
2A-3OBUArrowR-HSA-6798667 (Reactome)
2A-3OBUR-HSA-6798345 (Reactome)
ATPR-HSA-6798345 (Reactome)
Ac-CoAArrowR-HSA-6798345 (Reactome)
CoA-SHR-HSA-6798345 (Reactome)
GCAT:PXLP dimer:TDH tetramermim-catalysisR-HSA-6798345 (Reactome)
GCAT:PXLP dimer:TDH tetramermim-catalysisR-HSA-6798667 (Reactome)
GlyArrowR-HSA-6798345 (Reactome)
H+ArrowR-HSA-6798345 (Reactome)
L-ThrR-HSA-6798667 (Reactome)
NAD+R-HSA-6798667 (Reactome)
NADHArrowR-HSA-6798667 (Reactome)
PPiArrowR-HSA-6798345 (Reactome)
R-HSA-6798345 (Reactome) The degradation of L-threonine to glycine in both prokaryotes and eukaryotes takes place through a two-step biochemical pathway. In the second step, mitochondrial 2-amino-3-ketobutyrate coenzyme A ligase (GCAT, aka KBL) catalyses the reaction between 2-amino-3-oxobutanoate (2A-3OBU) and coenzyme A (CoA-SH) to form glycine (Gly) and acetyl-CoA (Ac-CoA) (Edgar & Polak 2000). GCAT resides on the mitochondrial inner membrane and requires pyridoxal 5-phosphate (PXLP) as cofactor. It is strongly expressed in heart, brain, liver and pancreas. Dimeric GCAT:PXLP is thought to exist on the mitochondrial inner membrane in complex with tetrameric L-threonine 3-dehydrogenase (TDH), the first enzyme in this pathway (Tressel et al. 1986). With these two enzymes located together, it stops the rapid and spontaneous decarboxylation of 2A-3OBU to aminoacetone and carbon dioxide and instead, results in glycine formation.
R-HSA-6798667 (Reactome) The degradation of L-threonine to glycine in both prokaryotes and eukaryotes takes place through a two-step biochemical pathway. In the first step, L-threonine (L-Thr) is oxidised to 2-amino-3-oxobutanoate (2A-3OBU) using NAD+ as acceptor. This reaction is catalysed by mitochondrial L-threonine 3-dehydrogenase (TDH) (Edgar 2002). The human activity is inferred from the characterised porcine Tdh (Edgar 2002b, Kao & Davis 1994). TDH is thought to exist as a tetramer on the mitochondrial inner membrane in complex with dimeric 2-amino-3-ketobutyrate coenzyme A ligase (GCAT), the second enzyme in this pathway (Tressel et al. 1986). With these two enzymes located together, it stops the rapid and spontaneous decarboxylation of 2A-3OBU to aminoacetone and carbon dioxide and instead, results in glycine formation.
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