negative regulation of quinolinate biosynthetic process

Definition

Target type: biologicalprocess

Any process that stops, prevents or reduces the frequency, rate or extent of quinolinate biosynthetic process. [GO_REF:0000058, GOC:bf, GOC:PARL, GOC:TermGenie, PMID:12140278, PMID:19843166]

Negative regulation of quinolinate biosynthesis is a complex process that involves the coordinated action of multiple enzymes and regulatory factors. Quinolinate is an essential precursor for NAD biosynthesis, a crucial coenzyme involved in various metabolic reactions. Its production is tightly regulated to ensure adequate levels of NAD while preventing its accumulation to toxic levels.

The key enzyme involved in quinolinate biosynthesis is quinolinate phosphoribosyltransferase (QPRT), which catalyzes the conversion of quinolinate to nicotinate mononucleotide (NaMN), the first committed step in the NAD biosynthetic pathway. Negative regulation of quinolinate biosynthesis can occur at various levels, including:

1. **Transcriptional regulation:** The expression of QPRT gene can be suppressed by specific transcription factors, such as the NAD-dependent deacetylase SIRT1, which is activated under conditions of NAD depletion. This inhibition of QPRT expression reduces the production of quinolinate.

2. **Post-translational regulation:** QPRT activity can be modulated by post-translational modifications, such as phosphorylation, acetylation, and ubiquitination. These modifications can alter the enzyme's activity, stability, or localization, ultimately affecting quinolinate production.

3. **Metabolic feedback inhibition:** Quinolinate itself can feedback inhibit QPRT activity, thus limiting its own biosynthesis. This mechanism ensures that quinolinate levels are kept within a narrow range.

4. **Regulation by other metabolic pathways:** The biosynthesis of quinolinate can be influenced by the activity of other metabolic pathways, such as the kynurenine pathway. This pathway is involved in tryptophan catabolism and can contribute to the production of quinolinate.

5. **Regulation by cellular stress:** Cellular stress conditions, such as oxidative stress or DNA damage, can trigger the activation of specific signaling pathways that lead to the suppression of quinolinate biosynthesis.

Overall, negative regulation of quinolinate biosynthesis is a multi-layered process that involves various regulatory mechanisms aimed at maintaining cellular homeostasis and preventing the accumulation of toxic quinolinate levels.'
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Proteins (1)

Compounds (2)