Target type: biologicalprocess
The chemical reactions and pathways resulting in the biosynthesis of retinoic acid, one of the three components that makes up vitamin A. [GOC:hjd]
Retinoic acid (RA) biosynthesis is a multi-step process that converts retinol (vitamin A) into its active form, retinoic acid. This process is essential for normal development, growth, and cell differentiation.
The process begins with the uptake of retinol from the diet or from storage in the liver. Retinol is then transported to target cells where it is converted into retinaldehyde by the enzyme retinol dehydrogenase. Retinaldehyde is then oxidized to retinoic acid by the enzyme retinaldehyde dehydrogenase.
There are two major pathways for RA biosynthesis:
* **The classical pathway:** This pathway is primarily active in the liver and involves the sequential action of three enzymes: retinol dehydrogenase (RDH), retinaldehyde dehydrogenase (RALDH), and retinoic acid synthase (RALDH).
* **The alternative pathway:** This pathway is found in various tissues, including the skin, intestines, and lungs. This pathway uses a different set of enzymes, including short-chain dehydrogenase/reductase (SDR) and cytochrome P450 (CYP) enzymes.
The biosynthesis of RA is tightly regulated by several factors, including:
* **Vitamin A availability:** RA biosynthesis is directly dependent on the availability of retinol.
* **Enzyme expression and activity:** The expression and activity of enzymes involved in RA biosynthesis are regulated by various factors, including hormones, growth factors, and cellular signals.
* **Retinoic acid receptors (RARs):** RA binds to RARs, which are nuclear receptors that regulate gene expression. This feedback loop helps maintain appropriate RA levels in the body.
RA plays a crucial role in various biological processes, including:
* **Development and growth:** RA is essential for the proper development of organs, including the brain, heart, lungs, and limbs.
* **Cell differentiation:** RA regulates the differentiation of various cell types, including skin cells, immune cells, and epithelial cells.
* **Immune function:** RA modulates the immune response by influencing the development and function of immune cells.
* **Vision:** RA is essential for maintaining proper vision.
**Deficiencies or imbalances in RA biosynthesis can lead to various health issues, including:**
* **Birth defects:** Deficiencies in RA during embryonic development can lead to severe birth defects.
* **Skin disorders:** RA plays a role in skin cell differentiation and repair. Deficiencies can cause skin problems like acne, psoriasis, and keratosis pilaris.
* **Immune dysregulation:** Imbalances in RA levels can contribute to autoimmune disorders.
* **Cancer:** RA has been shown to have both anticancer and pro-cancer effects depending on the context.
In summary, RA biosynthesis is a complex and tightly regulated process that is essential for maintaining health and development. Understanding the process is crucial for developing treatments for diseases related to RA deficiency or excess.'
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Protein | Definition | Taxonomy |
---|---|---|
Retinal dehydrogenase 2 | A retinal dehydrogenase 2 that is encoded in the genome of chicken. [OMA:O93344, PRO:DNx] | Gallus gallus (chicken) |
Aldehyde dehydrogenase family 1 member A3 | A retinaldehyde dehydrogenase 3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P47895] | Homo sapiens (human) |
Retinal dehydrogenase 2 | A retinal dehydrogenase 2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O94788] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
uvitex swn | Uvitex SWN: optical brightner from Ciba; structure | 7-aminocoumarins | fluorochrome |
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 |
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 |
7-butyl-8-[[4-(3-chlorophenyl)-1-piperazinyl]methyl]-1,3-dimethylpurine-2,6-dione | piperazines |