Retinoic acid

9-''cis''-retinoic acidRAretinoic acid gradientRetinoic acid response elements (RAREs)retinoid acidvitamin A acid
Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A required for growth and development.wikipedia
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Vitamin A

Avitamins ARAE
Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A required for growth and development.
Vitamin A is a group of unsaturated nutritional organic compounds that includes retinol, retinal, retinoic acid, and several provitamin A carotenoids (most notably beta-carotene).

Retinol

vitamin Aretinol metabolismA
Retinoic acid is a metabolite of vitamin A (retinol) that mediates the functions of vitamin A required for growth and development. Retinoic acid is responsible for most of the activity of vitamin A, save visual pigment effects that require retinal (retinaldehyde), and cell metabolism effects that may require retinol itself.
It is converted in the body to retinal and retinoic acid through which it acts.

Isotretinoin

13-cis retinoic acid13-cis-retinoic acidAccutane
The key role of retinoic acid in embryonic development mediates the high teratogenicity of retinoid pharmaceuticals, such as isotretinoin used for treatment of cancer and acne.
Isotretinoin is known to cause birth defects due to in-utero exposure because of the molecule's close resemblance to retinoic acid, a natural vitamin A derivative which controls normal embryonic development.

Hox gene

HoxHox genesHox'' genes
It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages.
In higher animals including humans, retinoic acid regulates differential expression of Hox genes along the anteroposterior axis.

Retinal

retinaldehydeall-trans-retinalretinylidene
Retinoic acid is responsible for most of the activity of vitamin A, save visual pigment effects that require retinal (retinaldehyde), and cell metabolism effects that may require retinol itself.
The other main forms of vitamin A, retinol, and a partially active form, retinoic acid, may both be produced from retinal.

Alcohol dehydrogenase

liver alcohol dehydrogenasealcohol dehydrogenasesADH
Enzymes that metabolize excess retinol to prevent toxicity include alcohol dehydrogenase and cytochrome P450(cyp26).
Another evolutionary purpose may be metabolism of the endogenous alcohol vitamin A (retinol), which generates the hormone retinoic acid, although the function here may be primarily the elimination of toxic levels of retinol.

Retinol dehydrogenase

The enzyme that generate retinoic acid for control of gene expression include retinol dehydrogenase (i.e. Rdh10) that metabolize retinol to retinal, and retinal dehydrogenase: RALHD1 (ALDH1A1), RALHD2 (ALDH1A2), and RALHD3 (ALDH1A3) that metabolize retinal to retinoic acid.
The conversion of retinol to retinal is the rate-limiting step in the retinoic acid biosynthesis.

Retinal dehydrogenase

The enzyme that generate retinoic acid for control of gene expression include retinol dehydrogenase (i.e. Rdh10) that metabolize retinol to retinal, and retinal dehydrogenase: RALHD1 (ALDH1A1), RALHD2 (ALDH1A2), and RALHD3 (ALDH1A3) that metabolize retinal to retinoic acid.
The 3 substrates of this enzyme are retinal, NAD +, and H 2 O, whereas its 3 products are retinoic acid, NADH, and H +.

Acne

acne vulgariscystic acneblemishes
The key role of retinoic acid in embryonic development mediates the high teratogenicity of retinoid pharmaceuticals, such as isotretinoin used for treatment of cancer and acne.
Decreased levels of retinoic acid in the skin may contribute to comedo formation.

Xerophthalmia

dry eyesxerophthalmic
Thus, if animals are fed only retinoic acid but no vitamin A (retinol or retinal), they suffer none of the growth-stunting or epithelial-damaging effects of lack of vitamin A (including no xerophthalmia—dryness of the cornea).
Xerophthalmia from hypovitaminosis A is specifically due to lack of the hormone-like vitamin A metabolite retinoic acid, since (along with certain growth-stunting effects) the condition can be reversed in vitamin A deficient rats by retinoic acid supplementation (however the retinal damage continues).

Cytochrome P450

cytochrome P-450cytochrome P450 oxidaseCYP
Enzymes that metabolize excess retinol to prevent toxicity include alcohol dehydrogenase and cytochrome P450(cyp26).
The classes of CYPs most often investigated in non-human animals are those either involved in development (e.g., retinoic acid or hormone metabolism) or involved in the metabolism of toxic compounds (such as heterocyclic amines or polyaromatic hydrocarbons).

Tretinoin

all-trans retinoic acidall-''trans'' retinoic acidall-trans-retinoic acid
Tretinoin (Tradename: Retin-A)
The origin of the name tretinoin is uncertain, although several sources agree (one with probability, one with asserted certainty ) that it probably comes from trans- + retinoic [acid] + -in, which is plausible given that tretinoin is the all-trans isomer of retinoic acid.

Chordate

Chordatachordatesnerve cord
Retinoic acid is required in chordate animals, which includes all higher animals from fish to humans.

Embryonic development

embryogenesisdevelopmentembryo development
During early embryonic development, retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo.

Teratology

teratogenicteratogenteratogenicity
The key role of retinoic acid in embryonic development mediates the high teratogenicity of retinoid pharmaceuticals, such as isotretinoin used for treatment of cancer and acne.

Retinoic acid receptor

RARretinoic acidretinoic acid receptor (RAR)
Retinoic acid acts by binding to the retinoic acid receptor (RAR), which is bound to DNA as a heterodimer with the retinoid X receptor (RXR) in regions called retinoic acid response elements (RAREs).

Retinoid X receptor

RXRretinoid X receptor (RXR)retinoid X receptors
Retinoic acid acts by binding to the retinoic acid receptor (RAR), which is bound to DNA as a heterodimer with the retinoid X receptor (RXR) in regions called retinoic acid response elements (RAREs).

Hypogonadism

low testosterone levelslow sex hormone levelslow testosterone levels in men
In addition, vitamin A-deprived but retinoic acid-supplemented male rats exhibit hypogonadism and infertility due to lack of local retinoic acid synthesis in the testis; similar treatment of female rats causes infertility due to fetal resorption caused by a lack of local retinoic acid synthesis in the embryo.

Infertility

infertilesterilesterility
In addition, vitamin A-deprived but retinoic acid-supplemented male rats exhibit hypogonadism and infertility due to lack of local retinoic acid synthesis in the testis; similar treatment of female rats causes infertility due to fetal resorption caused by a lack of local retinoic acid synthesis in the embryo.

Spermatogenesis

spermatogenicsperm productionproduction of sperm
Suppressing this enzyme has been proposed as a possible way to make a male contraceptive pill, because retinoic acid is necessary for spermatogenesis in humans, much as in rats.

Protein Data Bank

PDBProtein Data Bank (PDB)RCSB
* Retinoic acid bound to proteins in the PDB

Retinoid X receptor alpha

RXRANR2B1RXRα
Retinoid X receptors (RXRs) and retinoic acid receptors (RARs), are nuclear receptors that mediate the biological effects of retinoids by their involvement in retinoic acid-mediated gene activation.

Development of the digestive system

primitive gut
Different regions of the gut tube such as the esophagus, stomach, duodenum, etc. are specified by a retinoic acid gradient that causes transcription factors unique to each region to be expressed.

P19 cell

embryonic carcinoma
Also, exposing P19 cells to retinoic acid (RA) can differentiate them into neuronal cells.

TFAP2A

transcription factor AP-2 alpha (activating enhancer binding protein 2 alpha)
AP2-alpha is a 52-kD retinoic acid-inducible and developmentally regulated activator of transcription that binds to a consensus DNA-binding sequence GCCNNNGGC in the SV40 and metallothionein promoters.