Target type: molecularfunction
Binding to thiamine pyrophosphate, the diphosphoric ester of thiamine. Acts as a coenzyme of several (de)carboxylases, transketolases, and alpha-oxoacid dehydrogenases. [GOC:mlg]
Thiamine pyrophosphate (TPP) binding is a crucial molecular function that plays a pivotal role in a wide range of metabolic pathways. TPP, the active form of thiamine (vitamin B1), acts as a cofactor for a diverse set of enzymes, primarily involved in carbohydrate metabolism. Its unique structure, featuring a thiazole ring and a pyrimidine ring connected by a methylene bridge, allows TPP to participate in several key enzymatic reactions:
1. **Decarboxylation:** TPP facilitates the removal of a carboxyl group (CO2) from alpha-keto acids, such as pyruvate and alpha-ketoglutarate. This reaction is central to glycolysis and the citric acid cycle, respectively.
2. **Carbon-carbon bond formation:** TPP acts as a carrier of activated one-carbon units, enabling the formation of new carbon-carbon bonds. For instance, in the transketolase reaction of the pentose phosphate pathway, TPP transfers a two-carbon unit from a ketose sugar to an aldose sugar.
3. **Isomerization:** TPP participates in the isomerization of certain substrates, like the conversion of glyceraldehyde-3-phosphate to dihydroxyacetone phosphate in glycolysis.
4. **Oxidative decarboxylation:** In the pyruvate dehydrogenase complex, TPP facilitates the oxidative decarboxylation of pyruvate to acetyl-CoA, a critical step in linking glycolysis to the citric acid cycle.
The mechanism of TPP binding involves the formation of a covalent adduct with the enzyme. The thiazole ring of TPP forms a carbanion, which attacks the carbonyl group of the substrate. This leads to the formation of an enzyme-TPP-substrate intermediate, facilitating the catalytic reaction. The interaction between TPP and the enzyme is highly specific, ensuring the correct positioning of the substrate and the efficient transfer of chemical groups.
The binding of TPP to enzymes is essential for their catalytic activity. Deficiency in thiamine can lead to a range of metabolic disorders, including beriberi, Wernicke-Korsakoff syndrome, and impaired brain function. Therefore, adequate thiamine intake is crucial for maintaining normal metabolic processes and overall health.'
"
| Protein | Definition | Taxonomy |
|---|---|---|
| 1-deoxy-D-xylulose-5-phosphate synthase | A 1-deoxy-D-xylulose-5-phosphate synthase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P77488] | Escherichia coli K-12 |
| Thiamine-binding periplasmic protein | A thiamine-binding periplasmic protein that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P31550] | Escherichia coli K-12 |
| Transketolase | A transketolase that is encoded in the genome of human. [PRO:DNx, UniProtKB:P29401] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| thiamine | thiamine(1+) : A primary alcohol that is 1,3-thiazol-3-ium substituted by (4-amino-2-methylpyrimidin-5-yl)methyl, methyl and 2-hydroxyethyl groups at positions 3, 4 and 5, respectively. | primary alcohol; vitamin B1 | Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| 1-nitroso-2-naphthol | naphthols | ||
| 4-nitrosodimethylaniline | 4-nitrosodimethylaniline: structure; RN given refers to parent cpd N,N-dimethyl-4-nitrosoaniline : A member of the class of dimethylanilines that is N,N-dimethylaniline having a nitroso group at the 4-position. | dimethylaniline; nitroso compound; tertiary amino compound | |
| nitrosobenzene | benzenes; nitroso compound | xenobiotic metabolite | |
| 2-nitrosotoluene | |||
| thiamine thiazolone pyrophosphate | thiamine thiazolone pyrophosphate: structure |