Target type: biologicalprocess
The chemical reactions and pathways resulting in the breakdown of tryptophan into other compounds, including acetyl-CoA. [GOC:go_curators]
Tryptophan catabolism to acetyl-CoA is a complex metabolic pathway that involves multiple enzymatic steps and occurs primarily in the liver. Here's a breakdown of the process:
1. **Tryptophan Degradation to Kynurenine:** The first step involves the enzyme **tryptophan dioxygenase (TDO)** or **indoleamine 2,3-dioxygenase (IDO)**, which catalyzes the oxidation of tryptophan to N-formylkynurenine. This step is regulated by various factors, including nutritional status, hormonal signals, and inflammatory cytokines.
2. **N-Formylkynurenine to Kynurenine:** N-formylkynurenine is then hydrolyzed to kynurenine by **formylkynurenine formamidase**.
3. **Kynurenine Metabolism:** Kynurenine undergoes a series of reactions, leading to the production of various metabolites, including:
- **Kynurenic Acid:** This metabolite is a potent inhibitor of the NMDA receptor, playing a role in neuroprotection and neurotoxicity.
- **3-Hydroxykynurenine:** This metabolite is further metabolized to **3-hydroxyanthranilic acid** (3-HAA).
4. **3-Hydroxyanthranilic Acid (3-HAA) to Quinolinate:** 3-HAA is then converted to **quinolinate**, a precursor for NAD+.
5. **Quinolinate to Nicotinamide Adenine Dinucleotide (NAD+):** Quinolinate is used in the biosynthesis of **NAD+**, a crucial coenzyme involved in numerous metabolic reactions.
6. **Alternative Pathway: Kynurenine to Anthranilate:** A separate pathway exists where kynurenine can be converted to **anthranilate** by **kynureninase**. Anthranilate can then be further metabolized to **picolinate**, a precursor for NAD+.
7. **Acetyl-CoA Production:** The key point to note is that **tryptophan catabolism does not directly produce acetyl-CoA**. Instead, the degradation of tryptophan through the kynurenine pathway yields metabolites that are essential for other metabolic processes, including NAD+ biosynthesis. Acetyl-CoA is generated through other pathways, such as the breakdown of carbohydrates (glycolysis) and fatty acids (beta-oxidation).
In summary, while tryptophan catabolism to acetyl-CoA is not a direct process, it's an essential pathway that contributes to the production of important metabolites like NAD+, which plays a vital role in cellular energy metabolism. The kynurenine pathway also has significant implications for neurotransmission, inflammation, and immune function.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Tryptophan 2,3-dioxygenase | A tryptophan 2,3-dioxygenase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P48775] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| tryptophan | tryptophan : An alpha-amino acid that is alanine bearing an indol-3-yl substituent at position 3. Tryptophan: An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals. | erythrose 4-phosphate/phosphoenolpyruvate family amino acid; L-alpha-amino acid; L-alpha-amino acid zwitterion; proteinogenic amino acid; tryptophan; tryptophan zwitterion | antidepressant; Escherichia coli metabolite; human metabolite; micronutrient; mouse metabolite; nutraceutical; plant metabolite; Saccharomyces cerevisiae metabolite |
| chaetochromin | chaetochromin: from Chaetomium spp.; RN given refers to chaetochromin A | ||
| norharman | beta-carboline : The parent compound of the beta-carbolines, a tricyclic structure comprising an indole ring system ortho- fused to C-3 and C-4 of a pyridine ring. norharman: RN given refers to parent cpd | beta-carbolines; mancude organic heterotricyclic parent | fungal metabolite; marine metabolite |
| tryptanthrine | tryptanthrine: minor constituent of traditional Chinese medicine qing dai | alkaloid antibiotic; organic heterotetracyclic compound; organonitrogen heterocyclic compound | |
| 4-(2-thiazolylazo)resorcinol | 4-(2-thiazolylazo)resorcinol: sensitive indicator for metals | ||
| celastrol | monocarboxylic acid; pentacyclic triterpenoid | anti-inflammatory drug; antineoplastic agent; antioxidant; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; Hsp90 inhibitor; metabolite | |
| cryptotanshinone | cryptotanshinone: from Salvia miltiorrhiza | abietane diterpenoid | anticoronaviral agent |
| tanshinone ii a | tashinone IIA: a cardiovascular agent with antineoplastic activity; isolated from Salvia miltiorrhiza; structure in first source | abietane diterpenoid | |
| nsc 36398 | NSC 36398: structure in first source | ||
| harman | harman : An indole alkaloid fundamental parent with a structure of 9H-beta-carboline carrying a methyl substituent at C-1. It has been isolated from the bark of Sickingia rubra, Symplocus racemosa, Passiflora incarnata, Peganum harmala, Banisteriopsis caapi and Tribulus terrestris, as well as from tobacco smoke. It is a specific, reversible inhibitor of monoamine oxidase A. harman: a beta-carboline; RN given refers to parent cpd; structure | harmala alkaloid; indole alkaloid; indole alkaloid fundamental parent | anti-HIV agent; EC 1.4.3.4 (monoamine oxidase) inhibitor; plant metabolite |
| 680c91 | 680C91 : A fluoroindole that is 6-fluoroindole in which the hydrogen at position 3 has been replaced by a 2-(pyridin-3-yl)vinyl group (trans configuration). It is a selective inhibitor of tryptophan 2,3-dioxygenase (TDO), which directs the conversion of trypophan to kynurenin. | fluoroindole; olefinic compound; pyridines | EC 1.13.11.11 (tryptophan 2,3-dioxygenase) inhibitor |
| beta-3-oxindolylalanine | beta-3-oxindolylalanine: main intermediate in tryptophan degration occurring in acid hydrolysis of protein | ||
| stf 083010 | STF 083010: inhibits Ire1 endonuclease; structure in first source |