Page last updated: 2024-10-24

all-trans retinoic acid 4-hydrolase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: all-trans-retinoate + O2 + reduced [NADPH--hemoprotein reductase] = all-trans-(4S)-hydroxyretinoate + H+ + H2O + oxidized [NADPH--hemoprotein reductase]. [PMID:9250660, PMID:9716180, RHEA:51492]

All-trans retinoic acid 4-hydrolase activity refers to the enzymatic ability to catalyze the hydrolysis of all-trans retinoic acid (ATRA) at the 4-position, resulting in the formation of 4-hydroxy-retinoic acid. This reaction is critical for the metabolism of ATRA, a biologically active form of vitamin A, and plays a crucial role in regulating various cellular processes.

ATRA is a key signaling molecule involved in cell growth, differentiation, and apoptosis. It exerts its effects by binding to retinoic acid receptors (RARs), which are nuclear transcription factors. Upon binding ATRA, RARs activate the expression of specific genes, leading to changes in cellular behavior.

The hydrolytic cleavage of ATRA by all-trans retinoic acid 4-hydrolase activity is essential for controlling the levels of ATRA in the body. This enzyme helps to prevent the accumulation of ATRA to toxic levels, ensuring proper signaling and preventing adverse effects.

Moreover, 4-hydroxy-retinoic acid, the product of this hydrolytic reaction, is also a biologically active retinoid. However, it exhibits different binding affinities to RAR subtypes compared to ATRA, leading to distinct biological effects.

In conclusion, all-trans retinoic acid 4-hydrolase activity plays a critical role in ATRA metabolism by modulating its levels and converting it to 4-hydroxy-retinoic acid. This enzymatic activity is essential for regulating ATRA signaling pathways, ensuring appropriate cellular responses and maintaining homeostasis.'
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Proteins (1)

ProteinDefinitionTaxonomy
Cytochrome P450 26A1A cytochrome P450 26A1 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O43174]Homo sapiens (human)

Compounds (5)

CompoundDefinitionClassesRoles
ketoconazole1-acetyl-4-(4-{[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy}phenyl)piperazine : A dioxolane that is 1,3-dioxolane which is substituted at positions 2, 2, and 4 by imidazol-1-ylmethyl, 2,4-dichlorophenyl, and [para-(4-acetylpiperazin-1-yl)phenoxy]methyl groups, respectively.dichlorobenzene;
dioxolane;
ether;
imidazoles;
N-acylpiperazine;
N-arylpiperazine
liarozoleliarozole: inhibits all-trans-retinoic acid 4-hydroxylase; effective against hormone-dependent and hormone-independent tumors; R 75251 is chlorohydrate of R 61405; a potent inhibitor of retinoic acid metabolism; USAN name - liarozole fumaratebenzimidazoles
bexarotenebenzoic acids;
naphthalenes;
retinoid
antineoplastic agent
sr 11237SR 11237: structure given in first source
r 115866N-{4-[2-ethyl-1-(1,2,4-triazol-1-yl)butyl]phenyl}-1,3-benzothiazol-2-amine : A member of the class of benzothiazoles that is 2-amino-1,3-benzothiazole in which one of the amino hydrogens is replaced by a 4-[2-ethyl-1-(1H-1,2,4-triazol-1-yl)butyl]phenyl group.

R 115866: structure in first source

talarozole : A racemate comprising equimolar amounts of (R)- and (S)-talarozole. It is used for the treatment of keratinization disorders, psoriasis and acne.
aromatic amine;
benzothiazoles;
secondary amino compound;
triazoles