Succinic semialdehyde

Last updated
Succinic semialdehyde
Succinic semialdehyde.png
Names
Preferred IUPAC name
4-Oxobutanoic acid
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.155.728 OOjs UI icon edit-ltr-progressive.svg
KEGG
MeSH Succinic+semialdehyde
PubChem CID
UNII
  • InChI=1S/C4H6O3/c5-3-1-2-4(6)7/h3H,1-2H2,(H,6,7) Yes check.svgY
    Key: UIUJIQZEACWQSV-UHFFFAOYSA-N Yes check.svgY
  • InChI=1/C4H6O3/c5-3-1-2-4(6)7/h3H,1-2H2,(H,6,7)
    Key: UIUJIQZEACWQSV-UHFFFAOYAS
  • O=CCCC(=O)O
Properties
C4H6O3
Molar mass 102.089 g/mol
Appearanceoil
Boiling point 135 °C (275 °F; 408 K) at 14 mmHg
soluble in water, ethanol, benzene, diethyl ether [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Succinic semialdehyde (SSA) is a GABA and GHB metabolite. It is formed from GABA by the action of GABA transaminase (4-aminobutyrate aminotransferase) and further oxidised to become succinic acid, which enters TCA cycle. SSA is oxidized into succinic acid by the enzyme succinic semialdehyde dehydrogenase, which uses NAD+ as a cofactor. [2] [3]   When the oxidation of succinic semialdehyde to succinic acid is impaired, accumulation of succinic semialdehyde takes place which leads to succinic semialdehyde dehydrogenase deficiency. [3]

In addition to the pathway involving GABA transaminase, gamma-hydroxybutyric acid (GHB) can also be metabolized to SSA via GHB dehydrogenase or by GHB transhydrogenase (D-2-hydroxyglutarate transhydrogenase). [4] [5] [6] [7]

See also

Related Research Articles

γ-Hydroxybutyric acid Chemical compound

γ-Hydroxybutyric acid, also known as gamma-hydroxybutyric acid, GHB, or 4-hydroxybutanoic acid, is a naturally occurring neurotransmitter and a depressant drug. It is a precursor to GABA, glutamate, and glycine in certain brain areas. It acts on the GHB receptor and is a weak agonist at the GABAB receptor. GHB has been used in the medical setting as a general anesthetic and as treatment for cataplexy, narcolepsy, and alcoholism. The substance is also used illicitly for various reasons, including as a performance-enhancing drug, date rape drug, and as a recreational drug.

<span class="mw-page-title-main">GABA</span> Main inhibitory neurotransmitter in the mammalian brain

GABA is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.

Depressants, colloquially known as "downers" or central nervous system (CNS) depressants, are drugs that lower neurotransmission levels, decrease the electrical activity of brain cells, or reduce arousal or stimulation in various areas of the brain. Some specific depressants do influence mood, either positively or negatively, but depressants often have no clear impact on mood. In contrast, stimulants, or "uppers", increase mental alertness, making stimulants the opposite drug class from depressants. Antidepressants are defined by their effect on mood, not on general brain activity, so they form an orthogonal category of drugs.

γ-Butyrolactone Chemical compound

γ-Butyrolactone (GBL) or gamma-butyrolactone is an organic compound with the formula O=CO(CH2)3. It is a hygroscopic, colorless, water-miscible liquid with a weak characteristic odor. It is the simplest 4-carbon lactone. It is mainly used as an intermediate in the production of other chemicals, such as N-methyl-2-pyrrolidone.

<span class="mw-page-title-main">Vigabatrin</span> Epilepsy medication

Vigabatrin, sold under the brand name Sabril among others, is a medication used in the management and treatment of infantile spasms and refractory complex partial seizures.

<span class="mw-page-title-main">Sodium oxybate</span> Medication to treat symptoms of narcolepsy

Sodium oxybate, sold under the brand name Xyrem among others, is a medication used to treat symptoms of narcolepsy: sudden muscle weakness and excessive daytime sleepiness. It is used sometimes in France and Italy as an anesthetic given intravenously; it is also approved and used in Italy and in Austria to treat alcohol dependence and alcohol withdrawal syndrome.

<span class="mw-page-title-main">Succinic semialdehyde dehydrogenase deficiency</span> Rare disorder involving deficiency in GABA degradation

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder of the degradation pathway of the inhibitory neurotransmitter γ-aminobutyric acid, or GABA. The disorder has been identified in approximately 350 families, with a significant proportion being consanguineous families. The first case was identified in 1981 and published in a Dutch clinical chemistry journal that highlighted a number of neurological conditions such as delayed intellectual, motor, speech, and language as the most common manifestations. Later cases reported in the early 1990s began to show that hypotonia, hyporeflexia, seizures, and a nonprogressive ataxia were frequent clinical features as well.

<span class="mw-page-title-main">4-Hydroxybutyrate dehydrogenase</span> Class of enzymes

In enzymology, a 4-hydroxybutyrate dehydrogenase (EC 1.1.1.61) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Succinate-semialdehyde dehydrogenase</span>

In enzymology, a succinate-semialdehyde dehydrogenase (SSADH) (EC 1.2.1.24) is an enzyme that catalyzes the chemical reaction

γ-Amino-β-hydroxybutyric acid Anticonvulsant drug

γ-Amino-β-hydroxybutyric acid (GABOB), also known as β-hydroxy-γ-aminobutyric acid (β-hydroxy-GABA), sold under the brand name Gamibetal among others, is an anticonvulsant which is used for the treatment of epilepsy in Europe, Japan, and Mexico. It is a GABA analogue, or an analogue of the neurotransmitter γ-aminobutyric acid (GABA), and has been found to be an endogenous metabolite of GABA.

<span class="mw-page-title-main">4-aminobutyrate transaminase</span> Class of enzymes

In enzymology, 4-aminobutyrate transaminase, also called GABA transaminase or 4-aminobutyrate aminotransferase, or GABA-T, is an enzyme that catalyzes the chemical reaction:

<span class="mw-page-title-main">Aldehyde dehydrogenase 5 family, member A1</span> Protein-coding gene in the species Homo sapiens

Succinate-semialdehyde dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ALDH5A1 gene.

<span class="mw-page-title-main">GHB receptor</span> GHB receptor coding gene in the species Homo sapiens

The γ-hydroxybutyrate (GHB) receptor (GHBR), originally identified as GPR172A, is an excitatory G protein-coupled receptor (GPCR) that binds the neurotransmitter and psychoactive drug γ-hydroxybutyric acid (GHB). As solute carrier family 52 member 2 (SLC52A2), it is also a transporter for riboflavin.

<span class="mw-page-title-main">NCS-382</span> Chemical compound

NCS-382 is a moderately selective antagonist for the GHB receptor. It blocks the effects of GHB in animals and has both anti-sedative and anticonvulsant effects. It has been proposed as a treatment for GHB overdose in humans as well as the genetic metabolic disorder succinic semialdehyde dehydrogenase deficiency (SSADHD), but has never been developed for clinical use.

γ-Hydroxyvaleric acid Chemical compound

γ-Hydroxyvaleric acid (GHV), also known as 4-methyl-GHB, is a designer drug related to γ-hydroxybutyric acid (GHB). It is sometimes seen on the grey market as a legal alternative to GHB, but with lower potency and higher toxicity, properties which have tended to limit its recreational use.

<i>gab</i> operon

The gab operon is responsible for the conversion of γ-aminobutyrate (GABA) to succinate. The gab operon comprises three structural genes – gabD, gabT and gabP – that encode for a succinate semialdehyde dehydrogenase, GABA transaminase and a GABA permease respectively. There is a regulatory gene csiR, downstream of the operon, that codes for a putative transcriptional repressor and is activated when nitrogen is limiting.

4-aminobutyrate---pyruvate transaminase is an enzyme with systematic name 4-aminobutanoate:pyruvate aminotransferase. This enzyme is a type of GABA transaminase, which degrades the neurotransmitter GABA. The enzyme catalyses the following chemical reaction

<span class="mw-page-title-main">ABAT</span> Protein-coding gene in the species Homo sapiens

4-Aminobutyrate aminotransferase is a protein that in humans is encoded by the ABAT gene. This gene is located in chromosome 16 at position of 13.2. This gene goes by a number of names, including, GABA transaminase, GABAT, 4-aminobutyrate transaminase, NPD009 etc. This gene is mainly and abundant located in neuronal tissues. 4-Aminobutyrate aminotransferase belongs to group of pyridoxal 5-phosphate-dependent enzyme which activates a large portion giving reaction to amino acids. ABAT is made up of two monomers of enzymes where each subunit has a molecular weight of 50kDa. It is identified that almost tierce of human synapses have GABA. GABA is a neurotransmitter that has different roles in different regions of the central and peripheral nervous systems. It can be found also in some tissues that do not have neurons. In addition, GAD and GABA-AT are responsible in regulating the concentration of GABA.

4-Aminobutanal, also known as γ-aminobutyraldehyde, 4-aminobutyraldehyde, or GABA aldehyde, is a metabolite of putrescine and a biological precursor of γ-aminobutyric acid (GABA). It can be converted into GABA by the actions of diamine oxidase (DAO) and aminobutyraldehyde dehydrogenase (ABALDH). Putrescine is converted into ABAL via monoamine oxidase B (MAO-B). However, biosynthesis of GABA from polyamines like putrescine is a minor metabolic pathway in the brain.

4-Amino-1-butanol, or 4-aminobutanol, also known as 4-hydroxybutylamine, is an alkanolamine and an analogue and precursor of the neurotransmitter γ-aminobutyric acid (GABA).

References

  1. Lide, David R. (1998), Handbook of Chemistry and Physics (87 ed.), Boca Raton, Florida: CRC Press, pp. 3–446, ISBN   0-8493-0594-2
  2. Peng, Qi; Yang, Min; Wang, Wei; Han, Lili; Wang, Guannan; Wang, Pengyue; Zhang, Jie; Song, Fuping (2014-12-20). "Activation of gab cluster transcription in Bacillus thuringiensis by γ-aminobutyric acid or succinic semialdehyde is mediated by the Sigma 54-dependent transcriptional activator GabR". BMC Microbiology. 14 (1): 306. doi: 10.1186/s12866-014-0306-3 . ISSN   1471-2180. PMC   4279683 . PMID   25527261.
  3. 1 2 Struys, E. A.; Jansen, E. E. W.; Gibson, K. M.; Jakobs, C. (December 2005). "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". Journal of Inherited Metabolic Disease. 28 (6): 913–920. doi:10.1007/s10545-005-0111-0. ISSN   0141-8955. PMID   16435183. S2CID   9956364.
  4. Busardò FP, Jones AW (January 2015). "GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome". Current Neuropharmacology. 13 (1): 47–70. doi:10.2174/1570159X13666141210215423. PMC   4462042 . PMID   26074743.
  5. Felmlee MA, Morse BL, Morris ME (January 2021). "γ-Hydroxybutyric Acid: Pharmacokinetics, Pharmacodynamics, and Toxicology". The AAPS Journal. 23 (1): 22. doi:10.1208/s12248-020-00543-z. PMC   8098080 . PMID   33417072.
  6. Taxon ES, Halbers LP, Parsons SM (May 2020). "Kinetics aspects of Gamma-hydroxybutyrate dehydrogenase". Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1868 (5): 140376. doi: 10.1016/j.bbapap.2020.140376 . PMID   31981617.
  7. Kamal RM, van Noorden MS, Franzek E, Dijkstra BA, Loonen AJ, De Jong CA (March 2016). "The Neurobiological Mechanisms of Gamma-Hydroxybutyrate Dependence and Withdrawal and Their Clinical Relevance: A Review". Neuropsychobiology. 73 (2): 65–80. doi:10.1159/000443173. hdl: 2066/158441 . PMID   27003176.