regulation of dopamine biosynthetic process
Definition
Target type: biologicalprocess
Any process that modulates the frequency, rate or extent of dopamine biosynthetic process. [GO_REF:0000058, GOC:bf, GOC:PARL, GOC:TermGenie]
Dopamine biosynthesis is a complex process that is tightly regulated at multiple levels. The rate-limiting step in dopamine synthesis is the conversion of L-tyrosine to L-DOPA by the enzyme tyrosine hydroxylase (TH). TH is a tetrameric enzyme that requires the cofactor tetrahydrobiopterin (BH4) for activity. The activity of TH is regulated by several factors, including:
* **Substrate availability:** The availability of L-tyrosine is a major determinant of dopamine synthesis. L-tyrosine is derived from the diet or from the breakdown of proteins.
* **Co-factor availability:** The availability of BH4 is also essential for TH activity. BH4 is synthesized from GTP by the enzyme GTP cyclohydrolase I.
* **Phosphorylation:** TH can be phosphorylated by several kinases, including protein kinase A (PKA) and calcium/calmodulin-dependent protein kinase II (CaMKII). Phosphorylation of TH can increase its activity.
* **Feedback inhibition:** Dopamine can inhibit TH activity through a negative feedback loop. This feedback loop helps to prevent excessive dopamine synthesis.
Once L-DOPA is produced, it is converted to dopamine by the enzyme aromatic L-amino acid decarboxylase (AADC). AADC is a pyridoxal phosphate-dependent enzyme that is widely distributed throughout the brain.
The regulation of dopamine synthesis is critical for normal brain function. Dysregulation of dopamine synthesis can lead to various neurological and psychiatric disorders, including Parkinson's disease, schizophrenia, and addiction.
In addition to the regulation of the enzymatic steps involved in dopamine synthesis, the availability of dopamine in the synapse is also influenced by the following:
* **Dopamine reuptake:** Dopamine that is released into the synapse is rapidly reabsorbed by presynaptic neurons via dopamine transporters. This reuptake process helps to terminate the action of dopamine and to prevent its accumulation in the synapse.
* **Dopamine metabolism:** Dopamine is metabolized by the enzymes monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). These enzymes break down dopamine into inactive metabolites.
The regulation of dopamine biosynthesis and signaling is a complex and multifaceted process that is essential for normal brain function. Disturbances in these processes can contribute to a variety of neurological and psychiatric disorders.'
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Proteins (1)
| Protein | Definition | Taxonomy |
|---|---|---|
| Aldehyde dehydrogenase, mitochondrial | An aldehyde dehydrogenase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:P05091] | Homo sapiens (human) |
Compounds (13)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| disulfiram | organic disulfide; organosulfur acaricide | angiogenesis inhibitor; antineoplastic agent; apoptosis inducer; EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor; EC 3.1.1.1 (carboxylesterase) inhibitor; EC 3.1.1.8 (cholinesterase) inhibitor; EC 5.99.1.2 (DNA topoisomerase) inhibitor; ferroptosis inducer; fungicide; NF-kappaB inhibitor | |
| thiram | thiram : An organic disulfide that results from the formal oxidative dimerisation of N,N-dimethyldithiocarbamic acid. It is widely used as a fungicidal seed treatment. Thiram: A dithiocarbamate chemical, used commercially in the rubber processing industry and as a fungicide. In vivo studies indicate that it inactivates the enzyme GLUTATHIONE REDUCTASE. It has mutagenic activity and may induce chromosomal aberrations. | organic disulfide | antibacterial drug; antifungal agrochemical; antiseptic drug |
| bis(1-piperidylthiocarbonyl)disulfide | bis(1-piperidylthiocarbonyl)disulfide: indicator for analysis of copper; structure | ||
| win 18446 | WIN 18446 : A carboxamide that is 1,8-diaminooctane in which a hydrogen attached to each of the amino groups has been replaced by a dichloroacetyl group. Inhibitor of aldehyde dehydrogenase 1a2 (ALDH1a2). Inhibits the biosynthesis of retinoic acid from retinol in neonatal and adult murine testis. It down-regulates sex related genes in zebrafish. | organochlorine compound; secondary carboxamide | EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor |
| 4-(diethylamino)benzaldehyde | 4-(diethylamino)benzaldehyde : A member of the class of benzaldehydes carrying a diethylamino substituent at position 4. | aromatic amine; benzaldehydes; tertiary amino compound | EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor |
| magnolol | biphenyls | ||
| daidzin | daidzein 7-O-beta-D-glucoside : A glycosyloxyisoflavone that is daidzein attached to a beta-D-glucopyranosyl residue at position 7 via a glycosidic linkage. It is used in the treatment of alcohol dependency (antidipsotropic). daidzin: a potent, selective, and reversible inhibitor of human mitochondrial aldehyde dehydrogenase | 7-hydroxyisoflavones 7-O-beta-D-glucoside; hydroxyisoflavone; monosaccharide derivative | plant metabolite |
| ononin | 4'-methoxyisoflavones; 7-hydroxyisoflavones 7-O-beta-D-glucoside; monosaccharide derivative | plant metabolite | |
| 7-butyl-8-[[4-(3-chlorophenyl)-1-piperazinyl]methyl]-1,3-dimethylpurine-2,6-dione | piperazines | ||
| n-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide | N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide: Cardioprotective Agent; a small-molecule activator of aldehyde dehydrogenase-2 that reduces ischemic damage to the heart | carbonyl compound; organohalogen compound | |
| daidzein | 7-hydroxyisoflavones | antineoplastic agent; EC 2.7.7.7 (DNA-directed DNA polymerase) inhibitor; EC 3.2.1.20 (alpha-glucosidase) inhibitor; phytoestrogen; plant metabolite | |
| prunetin | prunetin : A hydroxyisoflavone that is genistein in which the hydroxy group at position 7 is replaced by a methoxy group. prunetin: reduces herpes virus-1 plaque formation | 7-methoxyisoflavones; hydroxyisoflavone | anti-inflammatory agent; EC 1.2.1.3 [aldehyde dehydrogenase (NAD(+))] inhibitor; EC 1.3.1.22 [3-oxo-5alpha-steroid 4-dehydrogenase (NADP(+))] inhibitor; metabolite |
| 4'-hydroxychalcone | 4'-hydroxychalcone : A member of the class of chalcones that is trans-chalcone substituted by a hydroxy group at position 4'. 4'-hydroxychalcone: inhibits TNFalpha-induced NF-κB activation; structure in first source | chalcones; phenols | anti-inflammatory agent; antineoplastic agent |