Proline catabolism (Homo sapiens)

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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

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External references

DataNodes

Name	Type	Database reference	Comment
1PYR-5COOH	Metabolite	CHEBI:17388 (ChEBI)
ALDH4A1	Protein	P30038 (Uniprot-TrEMBL)
ALDH4A1 dimer	Complex	R-HSA-70674 (Reactome)
FAD	Metabolite	CHEBI:16238 (ChEBI)
FADH2	Metabolite	CHEBI:17877 (ChEBI)
H+	Metabolite	CHEBI:15378 (ChEBI)
H2O	Metabolite	CHEBI:15377 (ChEBI)
HPRO	Metabolite	CHEBI:18240 (ChEBI)
L-Glu5S	Metabolite	CHEBI:17232 (ChEBI)
L-Glu	Metabolite	CHEBI:29985 (ChEBI)
L-Pro	Metabolite	CHEBI:60039 (ChEBI)
NAD+	Metabolite	CHEBI:57540 (ChEBI)
NADH	Metabolite	CHEBI:57945 (ChEBI)
PRODH(1-?)	Protein	O43272 (Uniprot-TrEMBL)
PRODH2	Protein	Q9UF12 (Uniprot-TrEMBL)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	1PYR-5COOH	Arrow	R-HSA-70670 (Reactome)
	1PYR-5COOH	Arrow	R-HSA-8955817 (Reactome)
1PYR-5COOH			R-HSA-70667 (Reactome)
ALDH4A1 dimer		mim-catalysis	R-HSA-70679 (Reactome)
	FADH2	Arrow	R-HSA-70670 (Reactome)
	FADH2	Arrow	R-HSA-8955817 (Reactome)
FAD			R-HSA-70670 (Reactome)
FAD			R-HSA-8955817 (Reactome)
	H+	Arrow	R-HSA-70670 (Reactome)
	H+	Arrow	R-HSA-70679 (Reactome)
	H2O	Arrow	R-HSA-8955817 (Reactome)
H2O			R-HSA-70667 (Reactome)
H2O			R-HSA-70679 (Reactome)
HPRO			R-HSA-8955817 (Reactome)
	L-Glu5S	Arrow	R-HSA-70667 (Reactome)
L-Glu5S			R-HSA-70679 (Reactome)
	L-Glu	Arrow	R-HSA-70679 (Reactome)
L-Pro			R-HSA-70670 (Reactome)
NAD+			R-HSA-70679 (Reactome)
	NADH	Arrow	R-HSA-70679 (Reactome)
PRODH(1-?)		mim-catalysis	R-HSA-70670 (Reactome)
PRODH2		mim-catalysis	R-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).