Specific and non‐specific succinic semialdehyde reductases from rat brain: Isolation and properties

Rumigny, J.F.; Maître, Michel; Cash, Christopher D.; Mandel, P.

doi:10.1016/0014-5793(80)80924-0

Cited by 60 publications

(47 citation statements)

References 12 publications

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“…SSR2 activity does not vary significantly during the interval from birth to 60 days [14] and probably provides a rather constant capacity for GHB synthesis during this period when the GHB concentration in the brain is falling. SSA, the substrate for SSR2, has been measured in the adult mouse brain and found to range between 0.05 and 0.1 nmol/g [16].…”

Section: Discussionmentioning

confidence: 99%

“…SSA, the substrate for SSR2, has been measured in the adult mouse brain and found to range between 0.05 and 0.1 nmol/g [16]. This concentration (if it is also valid for the rat brain) is well below 2.8 x 10"5 M, the reported Km for SSR2 [14], and therefore any change in the SSA concen tration would be reflected directly in the rate of GHB synthesis by SSR2. Nothing, however, is known at pre sent about changes in the SSA concentration in the brain during the neonatal period in the rat, but any changes that occur must be determined by the balance between enzyme activities that synthesize and degrade SSA.…”

Section: Discussionmentioning

confidence: 99%

“…SSA reductase (SSR2), a largely cytosolic enzyme, which is specific for the conversion of SSA to GHB [14,15], is the only known enzyme for GHB synthesis. SSR2 activity does not vary significantly during the interval from birth to 60 days [14] and probably provides a rather constant capacity for GHB synthesis during this period when the GHB concentration in the brain is falling.…”

Section: Discussionmentioning

confidence: 99%

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Developmental Time Courses in the Brain and Kidney of Two Enzymes that Oxidize γ-Hydroxybutyrate

Nelson¹,

Kaufman²

1994

Dev Neurosci

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The postnatal developmental profiles of two enzymes that oxidize Γ-hydro-xybutyrate (GHB) were examined during the period when the brain concentration of GHB was changing from the higher fetal level (7 µM) to the lower adult level (2 µM). At 20 days of age, the maximal oxidative capacity (V_max of GBH dehydrogenase (GHB-D) in the brain reached a rate that was approximately 50% greater than either adult or 18-day fetal values. The V_max for GBH-oxoacid transhydrogenase (GHB-T) in the brain was negligible at 18 days of gestation but increased 40-fold by 20 days and 100-fold by 70 days after birth. In contrast to the brain, the GHB concentration in the kidney remained at approximately 65% of the adult level from birth to 15 days of age and then rose to adult levels. The activities of both GHB-D and GHB-T were 20% of their adult values in the newborn kidney, and both enzymes increased to near adult activities by 20 days. It appears that GHB-D is the predominant catabolic enzyme for GHB in the fetal and neonatal brain, whereas in the kidney both enzymes participate from the earliest time examined.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Developmental Time Courses in the Brain and Kidney of Two Enzymes that Oxidize γ-Hydroxybutyrate

Nelson¹,

Kaufman²

1994

Dev Neurosci

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“…(3) Succinic semialdehyde reductases (SSR, EC 1.1.1.2): Pure non-specific and specific SSA reductases from rat brain prepared as in [3] were employed and the assay methods were identical to those in [3].…”

Section: Methodsmentioning

confidence: 99%

“…From rat and human brain, two enzymes have been isolated which can reduce succinic semialdehyde (SSA) to GHB [2][3][4]. In each case, one of these enzymes was non-specific for this reaction and could reduce a wide range of aldehydes, whereas the other enzyme showed a high degree of specificity for SSA reduction.…”

Section: Introductionmentioning

confidence: 99%

Evidence that a specific succinic semialdehyde reductase is responsible for λ‐hydroxybutyrate synthesis in brain tissue slices

et al. 1981

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Immunohistochemical studies of the localization of neurons containing the enzyme that synthesizes dopamine, GABA, or ?-hydroxybutyrate in the rat substantia nigra and striatum

et al. 2000

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gamma-Hydroxybutyrate (GHB) is an endogenous metabolite of gamma-aminobutyric acid (GABA), which is synthesized in the neuronal compartment of the central nervous system. This substance possesses several properties that support its role as a neurotransmitter/neuromodulator in brain. In particular, it is synthesized by a specific pathway that transforms GABA into succinic semialdehyde via GABA-T activity; then succinic semialdehyde is converted into GHB by a specific succinic semialdehyde reductase (SSR). The last enzyme is considered as a marker for neurons that synthesize GHB. This compound binds in brain to receptors whose distribution, ontogenesis, kinetics, and pharmacology are specific. Endogenous GHB, but also GHB exogenously administered to rats, participate in the regulation of dopaminergic activity of the nigrostriatal pathway. To investigate the distribution of GHB neurons in this pathway and the anatomic relationships between dopaminergic and GHB neurons, immunocytochemical identification of dopamine, GABA, and GHB neurons was carried out in the substantia nigra and striatum of the rat. The following markers for these neurons were used: anti-tyrosine hydroxylase (TH) antibodies for dopamine neurons, anti-glutamate decarboxylase (GAD) antibodies for GABA neurons, and anti-succinic semialdehyde reductase (SSR) antibodies for GHB neurons. GABA neurons were studied because GAD and SSR co-exist frequently in the same neuron, and GABA alone also exerts its own regulatory effects on dopaminergic neurons. This study reveals the co-existence of GAD/SSR and GAD/SSR/TH in numerous neurons of the substantia nigra. However, some neurons appear to be only GAD or SSR positive. In the striatum, TH-positive terminals surround many GHB neurons. GAD innervation is abundant in close contact with unlabeled neurons in the caudate-putamen, whereas distinct SSR-positive punctuates are also present. The existence of SSR-reactive synapses and neurons was confirmed in the striatum at the electron microscopic level. On the basis of these results, a clear anatomo-functional relationship between GHB and dopamine networks cannot be defined; however, we propose the modulation by GHB of striatal intrinsic neurons that could then interfere with the presynaptic control of dopaminergic activity.

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Specific and non‐specific succinic semialdehyde reductases from rat brain: Isolation and properties

Cited by 60 publications

References 12 publications

Developmental Time Courses in the Brain and Kidney of Two Enzymes that Oxidize γ-Hydroxybutyrate

Developmental Time Courses in the Brain and Kidney of Two Enzymes that Oxidize γ-Hydroxybutyrate

Evidence that a specific succinic semialdehyde reductase is responsible for λ‐hydroxybutyrate synthesis in brain tissue slices

Immunohistochemical studies of the localization of neurons containing the enzyme that synthesizes dopamine, GABA, or ?-hydroxybutyrate in the rat substantia nigra and striatum

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