Human Metabolome Database: Showing metabocard for Succinic acid semialdehyde (HMDB0001259)

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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (4) Show 4 proteins XML

enzymes (4) Show 4 proteins

Record Information

Version

4.0

Status

Detected and Quantified

Creation Date

2005-11-16 15:48:42 UTC

Update Date

2020-09-18 17:04:34 UTC

HMDB ID

HMDB0001259

Secondary Accession Numbers

HMDB01259

Metabolite Identification

Common Name

Succinic acid semialdehyde

Description

Succinic acid semialdehyde (or succinate semialdehyde) is an intermediate in the catabolism of gamma-aminobutyrate or GABA (PMID: 16435183 ). It is formed from GABA by the action of GABA transaminase, which leads to the production of succinate semialdehyde and alanine. The resulting succinate semialdehyde is further oxidized by succinate semialdehyde dehydrogenase to become succinic acid, which also yields NADPH. Under certain situations, high levels of succinate semialdehyde can function as a neurotoxin and a metabotoxin. A neurotoxin is a compound that causes damage to the brain and nerve tissues. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Elevated serum levels of succinate semialdehyde are found in succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria), a rare neurometabolic disorder of gamma-aminobutyric acid (GABA) degradation. Symptoms include motor delay, hypotonia, speech delay, autistic features, seizures, and ataxia. Patients also exhibit behavioural problems such as attention deficit, hyperactivity, anxiety, or aggression (PMID: 18622364 ). Succinate semialdehyde is considered a reactive carbonyl and may lead to increased oxidative stress. This stress is believed to contribute to the formation of free radicals in the brain tissue of animal models induced with SSADH deficiency, which further leads to secondary cell damage and death. Additionally, oxidative stress may be responsible for the loss of striatal dopamine, which may contribute to the neuropathology of SSADH deficiency.

Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
3-Formylpropanoic acid	ChEBI
3-Formylpropionic acid	ChEBI
4-Oxobutanoate	ChEBI
beta-Formylpropionic acid	ChEBI
Semialdehyde succinique	ChEBI
Succinaldehydic acid	ChEBI
Succinate semialdehyde	ChEBI
Succinic semialdehyde	Kegg
3-Formylpropanoate	Generator
3-Formylpropionate	Generator
4-Oxobutanoic acid	Generator
b-Formylpropionate	Generator
b-Formylpropionic acid	Generator
beta-Formylpropionate	Generator
Β-formylpropionate	Generator
Β-formylpropionic acid	Generator
Succinaldehydate	Generator
2-Formylpropionic acid ethyl ester	HMDB
Butryaldehydate	HMDB
Butryaldehydic acid	HMDB
gamma-Oxybutyrate	HMDB
gamma-Oxybutyric acid	HMDB
Succinic semialdehyde, calcium salt	HMDB
Succinic acid semialdehyde	ChEBI

Chemical Formula

C₄H₆O₃

Average Molecular Weight

102.0886

Monoisotopic Molecular Weight

102.031694058

IUPAC Name

4-oxobutanoic acid

Traditional Name

succinic semialdehyde

CAS Registry Number

692-29-5

SMILES

OC(=O)CCC=O

InChI Identifier

InChI=1S/C4H6O3/c5-3-1-2-4(6)7/h3H,1-2H2,(H,6,7)

InChI Key

UIUJIQZEACWQSV-UHFFFAOYSA-N

Chemical Taxonomy

Description

belongs to the class of organic compounds known as straight chain fatty acids. These are fatty acids with a straight aliphatic chain.

Kingdom

Organic compounds

Super Class

Lipids and lipid-like molecules

Class

Fatty Acyls

Sub Class

Fatty acids and conjugates

Direct Parent

Straight chain fatty acids

Alternative Parents

Substituents

Straight chain fatty acid
Alpha-hydrogen aldehyde
Monocarboxylic acid or derivatives
Carboxylic acid
Carboxylic acid derivative
Organic oxygen compound
Organic oxide
Hydrocarbon derivative
Organooxygen compound
Carbonyl group
Aldehyde
Aliphatic acyclic compound

Molecular Framework

Aliphatic acyclic compounds

External Descriptors

aldehydic acid (CHEBI:16265 )
Fatty aldehydes (LMFA06000118 )

Ontology

Disposition

Route of exposure:

Enteral:

Ingestion

Source:

Biological:

Animal

Plant:

Biological location:

Organ and components:

Testicle

Biofluid and excreta:

Subcellular:

Cell and elements:

Extracellular

Process

Naturally occurring process:

Biological process:

Biochemical process:

Chemical reaction:

Lipid peroxidation

Cellular process:

Cell signaling

Biochemical pathway:

Role

Indirect biological role:

Industrial application:

Biological role:

Physical Properties

State

Solid

Experimental Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	Not Available	Not Available
LogP	Not Available	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	194 g/L	ALOGPS
logP	-0.47	ALOGPS
logP	-0.56	ChemAxon
logS	0.28	ALOGPS
pKa (Strongest Acidic)	4.13	ChemAxon
pKa (Strongest Basic)	-7	ChemAxon
Physiological Charge	-1	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	1	ChemAxon
Polar Surface Area	54.37 Å²	ChemAxon
Rotatable Bond Count	3	ChemAxon
Refractivity	22.61 m³·mol⁻¹	ChemAxon
Polarizability	9.26 Å³	ChemAxon
Number of Rings	0	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	No	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	View
GC-MS	GC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)	splash10-000i-9400000000-8e1cb554add6ed6c4e35	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)	splash10-000i-9300000000-f5403e2e858fded273ac	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-000i-9400000000-8e1cb554add6ed6c4e35	Spectrum
GC-MS	GC-MS Spectrum - GC-MS (Non-derivatized)	splash10-000i-9300000000-f5403e2e858fded273ac	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000i-9500000000-eb52f4d003b7d5b86b3d	Spectrum
GC-MS	GC-MS Spectrum - GC-EI-TOF (Non-derivatized)	splash10-000i-9600000000-463f366ebd0be24a0283	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positive	splash10-052f-9000000000-d9618eb947af434dcf2f	Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positive	splash10-05fr-9800000000-40373963cdda851ebfea	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)	splash10-000i-9000000000-bf9ebea7e4800559c111	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, negative	splash10-0udi-0900000000-64b3498f7cdd4597da6a	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 1V, negative	splash10-0udi-1900000000-9d47aab2400f1da945bc	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 2V, negative	splash10-0udi-1900000000-94e1ac309574efbe3903	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 2V, negative	splash10-0udi-3900000000-7ec96b67f820176c39d3	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 3V, negative	splash10-0udi-5900000000-7708b3a1c05b69363aa9	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - Orbitrap 3V, negative	splash10-0zfr-8900000000-12726b727f621ac971b7	Spectrum
LC-MS/MS	LC-MS/MS Spectrum - n/a 7V, negative	splash10-0089-9000000000-9eb7dd16da8275702c75	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Positive	splash10-000i-9200000000-e31b8066f970e1c178d1	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Positive	splash10-052u-9000000000-76526f6c67d7a67c1d07	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Positive	splash10-0a4l-9000000000-70e85383e59b46bc429f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 10V, Negative	splash10-0udi-5900000000-f1c2507387f92b6e1e3f	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 20V, Negative	splash10-0zgi-9400000000-ba1b880a90d3ace8beee	Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - 40V, Negative	splash10-052f-9000000000-971836bb1672ad33106e	Spectrum
1D NMR	1H NMR Spectrum	Not Available	Spectrum
2D NMR	[1H,13C] 2D NMR Spectrum	Not Available	Spectrum

Biological Properties

Cellular Locations

Cytoplasm
Extracellular
Membrane
Mitochondria

Biospecimen Locations

Cerebrospinal Fluid (CSF)
Urine

Tissue Locations

Testis

Pathways

Name	SMPDB/Pathwhiz	KEGG
Glutamate Metabolism
4-Hydroxybutyric Aciduria/Succinic Semialdehyde Dehydrogenase Deficiency		Not Available
Homocarnosinosis		Not Available
Hyperinsulinism-Hyperammonemia Syndrome		Not Available
2-Hydroxyglutric Aciduria (D And L Form)		Not Available

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Cerebrospinal Fluid (CSF)	Detected and Quantified	28.5 (24.0-33.0) uM	Adult (>18 years old)	Both	Normal	Geigy Scientific ...	details
Urine	Detected and Quantified	0.35 (0.14-0.54) umol/mmol creatinine	Adult (>18 years old)	Male	Normal	9869358	details
Urine	Detected and Quantified	0.39 (0.28-0.51) umol/mmol creatinine	Adult (>18 years old)	Female	Normal	9869358	details
Urine	Detected but not Quantified	Not Quantified	Not Specified	Not Specified	Normal	2338430	details

Abnormal Concentrations

Not Available

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

DBMET01476

Phenol Explorer Compound ID

Not Available

FooDB ID

KNApSAcK ID

Chemspider ID

KEGG Compound ID

BioCyc ID

BiGG ID

Wikipedia Link

Succinic semialdehyde

METLIN ID

6114

PubChem Compound

1112

PDB ID

Not Available

ChEBI ID

16265

Food Biomarker Ontology

Not Available

VMH ID

SUCSAL

References

Synthesis Reference

Bruce, R.; Sims, K.; Pitts, F. N., Jr. Synthesis and purification of succinic semialdehyde. Analytical Biochemistry (1971), 41(1), 271-3.

Material Safety Data Sheet (MSDS)

Download (PDF)

General References

Du L, Musson DG, Wang AQ: Stability studies of vorinostat and its two metabolites in human plasma, serum and urine. J Pharm Biomed Anal. 2006 Nov 16;42(5):556-64. Epub 2006 Jul 5. [PubMed:16824724 ]
Du L, Musson DG, Wang AQ: High turbulence liquid chromatography online extraction and tandem mass spectrometry for the simultaneous determination of suberoylanilide hydroxamic acid and its two metabolites in human serum. Rapid Commun Mass Spectrom. 2005;19(13):1779-87. [PubMed:15945019 ]
Hinshelwood A, McGarvie G, Ellis EM: Substrate specificity of mouse aldo-keto reductase AKR7A5. Chem Biol Interact. 2003 Feb 1;143-144:263-9. [PubMed:12604212 ]
Lee BC, Choe YS, Chi DY, Paik JY, Lee KH, Choi Y, Kim BT: 8-cyclopentadienyltricarbonyl 99mtc 8-oxooctanoic acid: a novel radiotracer for evaluation of medium chain fatty acid metabolism in the liver. Bioconjug Chem. 2004 Jan-Feb;15(1):121-7. [PubMed:14733591 ]
Parise RA, Holleran JL, Beumer JH, Ramalingam S, Egorin MJ: A liquid chromatography-electrospray ionization tandem mass spectrometric assay for quantitation of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamicacid, SAHA), and its metabolites in human serum. J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Aug 18;840(2):108-15. Epub 2006 May 24. [PubMed:16725386 ]
Struys EA, Jansen EE, Gibson KM, Jakobs C: Determination of the GABA analogue succinic semialdehyde in urine and cerebrospinal fluid by dinitrophenylhydrazine derivatization and liquid chromatography-tandem mass spectrometry: application to SSADH deficiency. J Inherit Metab Dis. 2005;28(6):913-20. [PubMed:16435183 ]
Knerr I, Gibson KM, Jakobs C, Pearl PL: Neuropsychiatric morbidity in adolescent and adult succinic semialdehyde dehydrogenase deficiency patients. CNS Spectr. 2008 Jul;13(7):598-605. [PubMed:18622364 ]

Enzymes

Enzyme Details

1. 4-aminobutyrate aminotransferase, mitochondrial

General function:: Involved in 4-aminobutyrate transaminase activity
Specific function:: Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine.
Gene Name:: ABAT
Uniprot ID:: P80404
Molecular weight:: 56438.405

Reactions

gamma-Aminobutyric acid + Oxoglutaric acid → Succinic acid semialdehyde + L-Glutamic acid	details

Enzyme Details

2. Succinate-semialdehyde dehydrogenase, mitochondrial

General function:: Involved in oxidoreductase activity
Specific function:: Catalyzes one step in the degradation of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
Gene Name:: ALDH5A1
Uniprot ID:: P51649
Molecular weight:: 57214.23

Reactions

Succinic acid semialdehyde + NAD + Water → Succinic acid + NADH	details
Succinic acid semialdehyde + NAD + Water → Succinic acid + NADH + Hydrogen Ion	details

Enzyme Details

3. Aflatoxin B1 aldehyde reductase member 2

General function:: Energy production and conversion
Specific function:: Catalyzes the NADPH-dependent reduction of succinic semialdehyde to gamma-hydroxybutyrate. May have an important role in producing the neuromodulator gamma-hydroxybutyrate (GHB). Has broad substrate specificity. Has NADPH-dependent aldehyde reductase activity towards 2-carboxybenzaldehyde, 2-nitrobenzaldehyde and pyridine-2-aldehyde (in vitro). Can reduce 1,2-naphthoquinone and 9,10-phenanthrenequinone (in vitro). Can reduce the dialdehyde protein-binding form of aflatoxin B1 (AFB1) to the non-binding AFB1 dialcohol. May be involved in protection of liver against the toxic and carcinogenic effects of AFB1, a potent hepatocarcinogen.
Gene Name:: AKR7A2
Uniprot ID:: O43488
Molecular weight:: 39588.65

Reactions

4-Hydroxybutyric acid + NADP → Succinic acid semialdehyde + NADPH	details

Enzyme Details

4. Hydroxyacid-oxoacid transhydrogenase, mitochondrial

General function:: Involved in oxidoreductase activity
Specific function:: Catalyzes the cofactor-independent reversible oxidation of gamma-hydroxybutyrate (GHB) to succinic semialdehyde (SSA) coupled to reduction of 2-ketoglutarate (2-KG) to D-2-hydroxyglutarate (D-2-HG). D,L-3-hydroxyisobutyrate and L-3-hydroxybutyrate (L-3-OHB) are also substrates for HOT with 10-fold lower activities.
Gene Name:: ADHFE1
Uniprot ID:: Q8IWW8
Molecular weight:: 50307.42

Reactions

4-Hydroxybutyric acid + Oxoglutaric acid → Succinic acid semialdehyde + D-2-Hydroxyglutaric acid	details

Showing metabocard for Succinic acid semialdehyde (HMDB0001259)

Structure for HMDB0001259 (Succinic acid semialdehyde)

Enzymes

Reactions

Reactions

Reactions

Reactions