Proline catabolism (Homo sapiens)

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2, 341mitochondrial intermembrane spacemitochondrial matrixH+H2OPRODH(1-?)FADL-ProALDH4A1 dimerNADHNAD+H+L-Glu5SPRODH2H2OL-Glu1PYR-5COOHFADH2H2OALDH4A1 HPRO2


Description

Proline is catabolized in two steps to yield L-glutamate gamma-semialdehyde, which can react further with glutamate to yield ornithine and alpha-ketoglutarate (annotated as a reaction of amino acid synthesis and interconversion) or with NAD+ to yield glutamate and NADH + H+ (Phang et al. 2001). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 70688
Reactome-version 
Reactome version: 73
Reactome Author 
Reactome Author: D'Eustachio, Peter

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Bibliography

  1. Forte-McRobbie CM, Pietruszko R.; ''Purification and characterization of human liver "high Km" aldehyde dehydrogenase and its identification as glutamic gamma-semialdehyde dehydrogenase.''; PubMed Europe PMC Scholia
  2. Geraghty MT, Vaughn D, Nicholson AJ, Lin WW, Jimenez-Sanchez G, Obie C, Flynn MP, Valle D, Hu CA.; ''Mutations in the Delta1-pyrroline 5-carboxylate dehydrogenase gene cause type II hyperprolinemia.''; PubMed Europe PMC Scholia
  3. Bender HU, Almashanu S, Steel G, Hu CA, Lin WW, Willis A, Pulver A, Valle D.; ''Functional consequences of PRODH missense mutations.''; PubMed Europe PMC Scholia
  4. Summitt CB, Johnson LC, Jönsson TJ, Parsonage D, Holmes RP, Lowther WT.; ''Proline dehydrogenase 2 (PRODH2) is a hydroxyproline dehydrogenase (HYPDH) and molecular target for treating primary hyperoxaluria.''; PubMed Europe PMC Scholia

History

CompareRevisionActionTimeUserComment
114998view16:53, 25 January 2021ReactomeTeamReactome version 75
113442view11:51, 2 November 2020ReactomeTeamReactome version 74
112828view18:34, 9 October 2020DeSlOntology Term : 'amino acid degradation pathway' added !
112775view16:17, 9 October 2020ReactomeTeamNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
1PYR-5COOHMetaboliteCHEBI:17388 (ChEBI)
ALDH4A1 ProteinP30038 (Uniprot-TrEMBL)
ALDH4A1 dimerComplexR-HSA-70674 (Reactome)
FADMetaboliteCHEBI:16238 (ChEBI)
FADH2MetaboliteCHEBI:17877 (ChEBI)
H+MetaboliteCHEBI:15378 (ChEBI)
H2OMetaboliteCHEBI:15377 (ChEBI)
HPROMetaboliteCHEBI:18240 (ChEBI)
L-Glu5SMetaboliteCHEBI:17232 (ChEBI)
L-GluMetaboliteCHEBI:29985 (ChEBI)
L-ProMetaboliteCHEBI:60039 (ChEBI)
NAD+MetaboliteCHEBI:57540 (ChEBI)
NADHMetaboliteCHEBI:57945 (ChEBI)
PRODH(1-?)ProteinO43272 (Uniprot-TrEMBL)
PRODH2ProteinQ9UF12 (Uniprot-TrEMBL)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
1PYR-5COOHArrowR-HSA-70670 (Reactome)
1PYR-5COOHArrowR-HSA-8955817 (Reactome)
1PYR-5COOHR-HSA-70667 (Reactome)
ALDH4A1 dimermim-catalysisR-HSA-70679 (Reactome)
FADH2ArrowR-HSA-70670 (Reactome)
FADH2ArrowR-HSA-8955817 (Reactome)
FADR-HSA-70670 (Reactome)
FADR-HSA-8955817 (Reactome)
H+ArrowR-HSA-70670 (Reactome)
H+ArrowR-HSA-70679 (Reactome)
H2OArrowR-HSA-8955817 (Reactome)
H2OR-HSA-70667 (Reactome)
H2OR-HSA-70679 (Reactome)
HPROR-HSA-8955817 (Reactome)
L-Glu5SArrowR-HSA-70667 (Reactome)
L-Glu5SR-HSA-70679 (Reactome)
L-GluArrowR-HSA-70679 (Reactome)
L-ProR-HSA-70670 (Reactome)
NAD+R-HSA-70679 (Reactome)
NADHArrowR-HSA-70679 (Reactome)
PRODH(1-?)mim-catalysisR-HSA-70670 (Reactome)
PRODH2mim-catalysisR-HSA-8955817 (Reactome)
R-HSA-70667 (Reactome) The interconversion of (S)-1-pyrroline-5-carboxylate (1PYR-5COOH) glutamate 5-semialdehyde (L-GluSS) is a spontaneous reaction (Scriver et al. 2001).
R-HSA-70670 (Reactome) The dehydrogenation (oxidation) of proline to L-1-pyrroline-5-carboxylate coupled to the conversion of FAD to FADH2 is the first step in proline breakdown (Bender et al. 2005). Proline dehydrogenase (PRODH), the enzyme that catalyzes this reaction, is found in liver, kidney, and brain cells, where it is tightly bound to the inner mitochondrial membrane.
R-HSA-70679 (Reactome) Mitochondrial delta-1-pyrroline-5-carboxylate dehydrogenase (ALDH4A1) catalyzes the reaction of L-glutamate gamma-semialdehyde and NAD+ to form glutamate and NADH + H+ (Hu et al. 1996). The enzyme is a dimer (Forte-McRobbie and Pietruszko 1986). ALDH4A1 mutations cause type II hyperprolinemia in vivo (Geraghty et al. 1998).
R-HSA-8955817 (Reactome) The catabolism of trans-4-hydroxy-L-proline (HPRO) and proline (L-Pro) (from endogenous and dietary sources of collagen) makes a significant contribution to the glyoxylate pool in humans. The dehydrogenation (oxidation) of HPRO/L-Pro to L-1-pyrroline-5-carboxylate (1PYR-5COOH) coupled to the conversion of FAD to FADH2 is the first step in proline catabolism. Proline dehydrogenases (PRODHs), located at the inner mitochondrial membrane mediate this reaction. Whereas PRODH prefers L-Pro as substrate, PRODH2 has a clear preference for HPRO (Summitt et al. 2015).
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