negative regulation of retinoic acid biosynthetic process

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of retinoic acid biosynthetic process. [GOC:TermGenie, GOC:yaf]

Negative regulation of retinoic acid biosynthetic process involves a complex interplay of enzymes and regulatory factors to control the production of retinoic acid, a crucial signaling molecule involved in various developmental and physiological processes. Retinoic acid biosynthesis begins with the conversion of retinol (vitamin A) to retinaldehyde, catalyzed by retinol dehydrogenase (RDH) enzymes. Subsequently, retinaldehyde is oxidized to retinoic acid by retinaldehyde dehydrogenases (RALDH) enzymes. The negative regulation of this process is crucial for maintaining appropriate levels of retinoic acid, preventing its accumulation and potential toxic effects. Various mechanisms contribute to this negative regulation, including:

1. **Transcriptional regulation of RDH and RALDH genes:** Specific transcription factors and signaling pathways can repress the expression of RDH and RALDH genes, thereby reducing the synthesis of retinaldehyde and retinoic acid. For example, retinoic acid itself can act as a negative feedback regulator by inhibiting the expression of RALDH genes.

2. **Post-translational modification of RDH and RALDH enzymes:** These enzymes can be subject to phosphorylation, acetylation, or ubiquitination, leading to altered activity or stability. For instance, phosphorylation of certain RDH enzymes can decrease their activity, reducing retinoic acid synthesis.

3. **Inhibition of RDH and RALDH enzymatic activity:** Specific inhibitors can bind to and block the active sites of RDH and RALDH enzymes, preventing their catalytic activity. For example, some small molecules have been identified that specifically inhibit RALDH enzymes.

4. **Regulation of retinoic acid degradation:** Retinoic acid can be inactivated by enzymatic degradation, mainly through oxidation and conjugation reactions. Increased activity of these degradation enzymes would lead to lower levels of retinoic acid.

5. **Competition for substrates:** Other metabolic pathways can compete with retinoic acid synthesis for shared substrates like retinol or retinaldehyde. This competition can reduce the availability of these substrates for retinoic acid production.

6. **Cellular localization:** The localization of RDH and RALDH enzymes within cells can influence the efficiency of retinoic acid production. For example, compartmentalization of these enzymes in specific cellular organelles or compartments can limit their access to substrates or cofactors.

Overall, negative regulation of retinoic acid biosynthesis ensures precise control over its production and prevents imbalances that could have detrimental effects on development and physiology. This intricate regulatory network involves multiple levels of control, from transcriptional regulation to post-translational modifications and enzymatic activity, ultimately safeguarding the proper functioning of retinoic acid signaling.'
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Proteins (2)

Compounds (40)