Any feedback?
Literature summary for 1.1.1.149 extracted from
- Physiopathological role of the enzymatic complex 5alpha-reductase and 3alpha/beta-hydroxysteroid oxidoreductase in the generation of progesterone and testosterone neuroactive metabolites (2020), Front. Neuroendocrinol., 57, 100836 .
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| cytosol | - |
Rattus norvegicus | 5829 | - |
| cytosol | - |
Homo sapiens | 5829 | - |
| cytosol | - |
Mus musculus | 5829 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5alpha-dihydroprogesterone + NADPH + H+ | Rattus norvegicus | - |
5alpha,20alpha-tetrahydroprogesterone + NADP+ | - |
r |  |
| 5alpha-dihydroprogesterone + NADPH + H+ | Homo sapiens | - |
5alpha,20alpha-tetrahydroprogesterone + NADP+ | - |
r | |
| 5alpha-dihydroprogesterone + NADPH + H+ | Mus musculus | - |
5alpha,20alpha-tetrahydroprogesterone + NADP+ | - |
r | |
| dihydrotestosterone + NADPH + H+ | Rattus norvegicus | reaction of EC 1.1.1.357 | 4-androsten-3alpha,17beta-diol + NADP+ | - |
r | |
| dihydrotestosterone + NADPH + H+ | Homo sapiens | reaction of EC 1.1.1.357 | 4-androsten-3alpha,17beta-diol + NADP+ | - |
r | |
| dihydrotestosterone + NADPH + H+ | Mus musculus | reaction of EC 1.1.1.357 | 4-androsten-3alpha,17beta-diol + NADP+ | - |
r | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | Q04828 | four human 3alpha-HSOR isozymes are described | - |
| Mus musculus | Q91WT7 | - |
- |
| Rattus norvegicus | - |
only one isoform in rats | - |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| amygdala | - |
Rattus norvegicus | - |
| amygdala | - |
Homo sapiens | - |
| amygdala | - |
Mus musculus | - |
| astrocyte | - |
Rattus norvegicus | - |
| astrocyte | - |
Homo sapiens | - |
| astrocyte | - |
Mus musculus | - |
| brain | - |
Rattus norvegicus | - |
| brain | - |
Homo sapiens | - |
| brain | analysis of 3alpha-HSOR mRNA distribution in the mouse brain by in situ hybridization has shown that this enzyme is co-localized with 5alpha-R type 1 in neurons of the cerebral cortex, hippocampus, olfactory bulb, amygdala and thalamus. And 3alpha-HSOR immunoreactivity is largely distributed in both white and gray matters | Mus musculus | - |
| cerebral cortex | - |
Rattus norvegicus | - |
| cerebral cortex | - |
Homo sapiens | - |
| cerebral cortex | - |
Mus musculus | - |
| glial cell | - |
Rattus norvegicus | - |
| glial cell | - |
Homo sapiens | - |
| glial cell | - |
Mus musculus | - |
| hippocampus | - |
Rattus norvegicus | - |
| hippocampus | - |
Homo sapiens | - |
| hippocampus | - |
Mus musculus | - |
| additional information | in addition to neurons, 3alpha-HSOR activity appears to be highly localized in glial cells, such as type 1 astrocytes in culture and oligodendrocytes, although, 3alpa-HSOR activity has not been detected in myelin membranes of the CNS | Homo sapiens | - |
| neuron | - |
Rattus norvegicus | - |
| neuron | - |
Homo sapiens | - |
| neuron | - |
Mus musculus | - |
| olfactory bulb | - |
Rattus norvegicus | - |
| olfactory bulb | - |
Mus musculus | - |
| oligodendrocyte | - |
Rattus norvegicus | - |
| oligodendrocyte | - |
Homo sapiens | - |
| oligodendrocyte | - |
Mus musculus | - |
| spinal cord | - |
Rattus norvegicus | - |
| spinal cord | - |
Mus musculus | - |
| thalamus | - |
Rattus norvegicus | - |
| thalamus | - |
Homo sapiens | - |
| thalamus | - |
Mus musculus | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| 5alpha-dihydroprogesterone + NADPH + H+ | - |
Rattus norvegicus | 5alpha,20alpha-tetrahydroprogesterone + NADP+ | - |
r | |
| 5alpha-dihydroprogesterone + NADPH + H+ | - |
Homo sapiens | 5alpha,20alpha-tetrahydroprogesterone + NADP+ | - |
r | |
| 5alpha-dihydroprogesterone + NADPH + H+ | - |
Mus musculus | 5alpha,20alpha-tetrahydroprogesterone + NADP+ | - |
r | |
| dihydrotestosterone + NADPH + H+ | reaction of EC 1.1.1.357 | Rattus norvegicus | 4-androsten-3alpha,17beta-diol + NADP+ | - |
r | |
| dihydrotestosterone + NADPH + H+ | reaction of EC 1.1.1.357 | Homo sapiens | 4-androsten-3alpha,17beta-diol + NADP+ | - |
r | |
| dihydrotestosterone + NADPH + H+ | reaction of EC 1.1.1.357 | Mus musculus | 4-androsten-3alpha,17beta-diol + NADP+ | - |
r | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| 3alpha-HSOR | - |
Rattus norvegicus |
| 3alpha-HSOR | - |
Homo sapiens |
| 3alpha-HSOR | - |
Mus musculus |
| 3alpha-hydroxysteroid oxidoreductase | - |
Rattus norvegicus |
| 3alpha-hydroxysteroid oxidoreductase | - |
Homo sapiens |
| 3alpha-hydroxysteroid oxidoreductase | - |
Mus musculus |
| AKR1C1 | - |
Homo sapiens |
| AKR1C14 | - |
Mus musculus |
| AKR1C9 | - |
Rattus norvegicus |
| More | cf. EC 1.1.1.50, see also EC 1.1.1.357 | Rattus norvegicus |
| More | see also EC 1.1.1.357 | Homo sapiens |
| More | see also EC 1.1.1.357 | Mus musculus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| NADPH | - |
Rattus norvegicus | |
| NADPH | - |
Homo sapiens | |
| NADPH | - |
Mus musculus | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| evolution | 3alpha-HSOR is a member of the aldo-keto reductase superfamily | Rattus norvegicus |
| evolution | 3alpha-HSOR is a member of the aldo-keto reductase superfamily | Homo sapiens |
| evolution | 3alpha-HSOR is a member of the aldo-keto reductase superfamily | Mus musculus |
| malfunction | the expression of 5alpha-reductase (5alpha-R) and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR) and the levels of progesterone and testosterone reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. In other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5alpha-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. Changes in brain levels of PROG metabolites have been detected in Alzheimer's disease (AD) mouse models, such as the 3xTg-AD mouse | Mus musculus |
| malfunction | the expression of 5alpha-reductase (5alpha-R) and 3alpha-hydroxysteroid oxidoreductase (3alpha-HSOR) and the levels of progesterone and testosterone reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. A decrease in their nervous tissue levels may negatively impact the course and outcome of some pathological events. In other pathological conditions their increased levels may have a negative impact. Thus, the use of synthetic analogues of these steroids or 5alpha-R modulation have been proposed as therapeutic approaches for several nervous system pathologies. Low plasma testosterone levels are significantly associated with increased risk of Alzheimer's disease in elderly men, while higher free testosterone levels in women are associated with lower cerebral Abeta positivity | Homo sapiens |
| metabolism | the enzymatic complex 5alpha-reductase (5alpha-R) and 3alpha/3beta-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone and testosterone into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5alpha-R and 3alpha-HSOR and the levels of progesterone and testosterone reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. Biosynthesis of progesterone and testosterone metabolites and their mechanism of action, overview | Rattus norvegicus |
| metabolism | the enzymatic complex 5alpha-reductase (5alpha-R) and 3alpha/3beta-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone and testosterone into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5alpha-R and 3alpha-HSOR and the levels of progesterone and testosterone reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. Biosynthesis of progesterone and testosterone metabolites and their mechanism of action, overview | Homo sapiens |
| metabolism | the enzymatic complex 5alpha-reductase (5alpha-R) and 3alpha/3beta-hydroxysteroid oxidoreductase (HSOR) is expressed in the nervous system, where it transforms progesterone and testosterone into neuroactive metabolites. These metabolites regulate myelination, brain maturation, neurotransmission, reproductive behavior and the stress response. The expression of 5alpha-R and 3alpha-HSOR and the levels of progesterone and testosterone reduced metabolites show regional and sex differences in the nervous system and are affected by changing physiological conditions as well as by neurodegenerative and psychiatric disorders. Biosynthesis of progesterone and testosterone metabolites and their mechanism of action, overview | Mus musculus |
| physiological function | the enzymatic complex 5alpha-R and 3alpha-HSOR colocalizes in glutamatergic and GABAergic neurons of the cerebral cortex, hippocampus, amygdala and thalamus, suggesting that metabolites so formed are relevant for neurotransmitter synthesis and the modulation of their activity in these cells. The metabolites of progesterone and testosterone formed by the action of the enzymatic complex 5alpha-R and 3alpha- or 3beta-HSOR have a profound physiological impact in the nervous system, because they are also ligands for a variety of neuronal and glial receptors that are not directly modulated by progesterone and testosteron. The reduced metabolites of progesterone are also involved in mood regulation. Actions of progesterone and testosterone metabolites in physiological conditions, overview. The enzyme is involed in regulation of the levels of progesterone and testosterone reduced metabolites in the nervous system. Tetrahydroprogesterone (THP) treatment reduces seizures, prevents cell apoptosis in the spinal cord of STZ diabetic and protects against stroke, oxygen-glucose deprivation | Rattus norvegicus |
| physiological function | the enzymatic complex 5alpha-R and 3alpha-HSOR colocalizes in glutamatergic and GABAergic neurons of the cerebral cortex, hippocampus, amygdala and thalamus, suggesting that metabolites so formed are relevant for neurotransmitter synthesis and the modulation of their activity in these cells. The metabolites of progesterone and testosterone formed by the action of the enzymatic complex 5alpha-R and 3alpha- or 3beta-HSOR have a profound physiological impact in the nervous system, because they are also ligands for a variety of neuronal and glial receptors that are not directly modulated by progesterone and testosterone. The reduced metabolites of progesterone are also involved in mood regulation. Actions of progesterone and testosterone metabolites in physiological conditions, overview. The enzyme is involed in regulation of the levels of progesterone and testosterone reduced metabolites in the nervous system | Mus musculus |
| physiological function | the enzymatic complex 5alpha-R and 3alpha-HSOR colocalizes in glutamatergic and GABAergic neurons of the cerebral cortex, hippocampus, amygdala and thalamus, suggesting that metabolites so formed are relevant for neurotransmitter synthesis and the modulation of their activity in these cells. The metabolites of progesterone and testosterone formed by the action of the enzymatic complex 5alpha-R and 3alpha- or 3beta-HSOR have a profound physiological impact in the nervous system, because they are also ligands for a variety of neuronal and glial receptors that are not directly modulated by progesterone and testosterone. The reduced metabolites of progesterone are also involved in mood regulation. Actions of progesterone and testosterone metabolites in physiological conditions, overview. The enzyme is involed in regulation of the levels of progesterone and testosterone reduced metabolites in the nervous system. Metabolite of dihydrotestosterone (DHT), 4-androsten-3alpha,17beta-diol, exerts europrotective effects in SH-SY5Y neuronal cells and in primary cortical neurons, inhibiting the phosphorylation of extracellular signal-regulated kinase induced by amyloid beta peptide 1-42. Interestingly, this effect is mediated by both GABA-A receptor-dependent and independent mechanisms | Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
