Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80404 (GABA transaminase)
 786 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Electroencephalographic activity and gamma-Aminobutyric acid Transaminase together with Succinic semialdehyde dehydrogenase activity changes produced by sensitization with Prosopis juliflora pollen allergen were studied in the cerebral cortex and hypothalamus of the rat brain. Electrical activity of EEG recording begins to appear on 3rd day after sensitization with maximum increase in activity was found on day 9 and decreased after that. A sudden increase in electrical activity was produced in 9th day sensitized rat with 10 min after giving challenging dose intravenously. The measurement of enzymatic activity of GABA-T and SSA-DH showed decrease and increase in 3, 9, 15 and 30 days sensitized rat hypothalamus and cerebral cortex whole homogenate and mitochondrial fractions. A maximum changes in enzymatic activity was found in 9th day sensitized rat with significant alterations after giving sudden stress as challenging dose. These changes in EEG activity and GABA-ergic neurotransmitter in allergenic rats showed the immunoregulatory role of nervous system mediated via GABA shunt.
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PMID:Changes in the electroencephalographic and gamma-aminobutyric acid transaminase and succinic semialdehyde dehydrogenase in the allergen induced rat brain. 336 61

The effect of anticonvulsant drugs on the activity of enzymes responsible for the further metabolism of GABA has been studied in mouse brain homogenates. Slight inhibition (5 to 20%) of GABA-T activity was seen with chlordiazepoxide (0.1 mM), ethosuximide (0.1 mM) and di-n-propylacetate (0.1 mM). No anticonvulsant drug (even at a concentration of 10 mM) produced inhibition comparable to that seen with amino-oxyacetic acid (65% at 0.01 mM). Succinic semialdehyde dehydrogenase activity was inhibited by 10 to 20% at low concentrations (0.01 to 0.1 mM) of diazepam, carbamazepine, beclamide, acetazolamide, and di-n-propylacetate, and by 40% or more at high concentrations (2.5 to 10.0 mM) of diazepam, phenobarbital, carbamazepine, beclamide, and di-n-propylacetate. Interference with the further metabolism of GABA may contribute to the antiepileptic action of drugs or to the acute neurological toxicity of anticonvulsant agents.
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PMID:Effects of anticonvulsant drugs on the cerebral enzymes metabolizing GABA. 989 Jul 92

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal recessive disorder affecting CNS gamma-aminobutyric acid (GABA) degradation. SSADH, in conjunction with GABA transaminase, converts GABA to succinate. In the absence of SSADH, GABA is converted to 4-OH-butyrate. The presence of 4-OH-butyrate, a highly volatile compound, may be undetected on routine organic acid analysis. Urine organic acid testing was modified at the authors' institution in 1999 to screen for the excretion of 4-OH-butyrate by selective ion monitoring gas chromatography-mass spectrometry in addition to total ion chromatography. Since then, five patients with 4-hydroxybutyric aciduria have been identified. The authors add the clinical, neuroimaging, and EEG findings from a new cohort of patients to 51 patients reported in the literature with clinical details. Ages ranged from 1 to 21 years at diagnosis. Clinical findings include mild-moderate mental retardation, disproportionate language dysfunction, hypotonia, hyporeflexia, autistic behaviors, seizures, and hallucinations. Brain MRI performed in five patients at the authors' institution revealed symmetric increased T2 signal in the globus pallidi. SSADH deficiency is an under-recognized, potentially manageable neurometabolic disorder. Urine organic acid analysis should include a sensitive method for the detection of 4-hydroxybutyrate and should be obtained from patients with mental retardation or neuropsychiatric disturbance of unknown etiology.
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PMID:Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. 1274 23

Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare disorder characterized by an inborn error of the catabolism of the inhibitory neurotransmitter GABA. Because of the deficiency of SSADH, the final enzyme of the GABA degradation pathway, the substrate, succinic semialdehyde, is shunted towards production of 4-hydroxybutyric acid (gamma-hydroxybutyric acid). Elevations of gamma-hydroxybutyric acid can be detected in the physiologic fluids of patients with SSADH deficiency, and forms the mainstay of diagnosis. The clinical features of SSADH deficiency include nonspecific neurologic manifestations such as mental retardation/developmental delay, absent speech, hypotonia, nonprogressive ataxia, features of autism or pervasive developmental delay, developmental language delay (dyspraxia, receptive, and expressive delays), and occasionally, seizures. Although the metabolic pathway has been established, it is not known whether insufficient GABA and/or excess gamma-hydroxybutyric acid contribute to the disease phenotype. Pharmacological therapy in patients with this disorder has been limited to vigabatrin, an anticonvulsant that blocks GABA transaminase. This review will discuss therapeutic options in SSADH deficiency, on the basis of patient experience, and preliminary work using a murine model. Finally, a discussion of adjunctive therapies will be included.
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PMID:Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. 1289 56

Succinic semialdehyde dehydrogenase (SSADH) deficiency is an autosomal-recessively inherited disorder of gamma-aminobutyrate (GABA) catabolism characterized by ataxia and epilepsy. Since SSADH is responsible for GABA break-down downstream of GABA transaminase, patients manifest high extracellular levels of GABA, as well as the GABA(B) receptor (GABA(B)R) agonist gamma-hydroxybutyrate (GHB). SSADH knockout (KO) mice display absence seizures, which progress into lethal tonic-clonic seizures at around 3weeks of age. It is hypothesized that desensitization of GABA(B)Rs plays an important role in the disease, although detailed studies of pre- and postsynaptic GABA(B)Rs are not available. We performed patch-clamp recordings from layer 2/3 pyramidal neurons in neocortical brain slices of wild-type (WT) and SSADH KO mice. Electrical stimulation of GABAergic fibers during wash in of the GABA(B)R agonist baclofen revealed no difference in presynaptic GABA(B)R mediated inhibition of GABA release between WT and SSADH KO mice. In contrast, a significant decrease in postsynaptic baclofen-induced potassium currents was seen in SSADH KO mice. This reduction was unlikely to be caused by accumulation of potassium, GABA or GHB in the brain slices, or an altered expression of regulators of G-protein signaling (RGS) proteins. Finally, adenosine-induced potassium currents were also reduced in SSADH KO mice, which could suggest heterologous desensitization of the G-protein dependent effectors, leading to a reduction in G-protein coupled inwardly rectifying potassium (GIRK) channel responses. Our findings indicate that high GABA and GHB levels desensitize postsynaptic, but not certain presynaptic, GABA(B)Rs, promoting a decrease in GIRK channel function. These changes could contribute to the development of seizures in SSADH KO mice and potentially also in affected patients.
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PMID:Plasticity of postsynaptic, but not presynaptic, GABAB receptors in SSADH deficient mice. 2057 Jun 75