tetrahydrofolylpolyglutamate synthase activity
Definition
Target type: molecularfunction
Catalysis of the reaction: ATP + tetrahydrofolyl-(Glu)(n) + L-glutamate = ADP + phosphate + tetrahydrofolyl-(Glu)(n+1). [EC:6.3.2.17]
Tetrahydrofolylpolyglutamate synthase (FPGS) catalyzes the addition of glutamate residues to tetrahydrofolic acid (THF), forming tetrahydrofolylpolyglutamates (THFPGs). These polyglutamated derivatives are crucial for the proper functioning of numerous folate-dependent enzymes involved in essential metabolic pathways.
The enzyme's active site binds both THF and glutamate, facilitating the formation of a covalent intermediate between the γ-carboxyl group of glutamate and the γ-nitrogen of THF. This intermediate undergoes a series of steps, including nucleophilic attack by the α-amino group of glutamate, resulting in the formation of a peptide bond. The process is repeated, extending the polyglutamate chain attached to THF.
The polyglutamylation of THF has several key consequences:
1. **Increased affinity for folate-dependent enzymes:** The polyglutamate tail enhances the affinity of THF for enzymes, allowing for more efficient utilization of folate in metabolic reactions.
2. **Increased retention within cells:** The polyglutamylation of THF reduces its permeability across cellular membranes, promoting its intracellular retention and ensuring adequate levels for essential enzymatic reactions.
3. **Modulation of enzyme activity:** The length of the polyglutamate chain can influence the activity of different folate-dependent enzymes. For example, some enzymes require a specific length of the chain for optimal function.
Overall, tetrahydrofolylpolyglutamate synthase activity is vital for the proper utilization of folate in cellular metabolism. It plays a crucial role in maintaining the levels of tetrahydrofolylpolyglutamates, which are essential coenzymes for numerous metabolic processes, including nucleotide biosynthesis, amino acid metabolism, and the production of essential molecules like heme and neurotransmitters.'
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Proteins (3)
| Protein | Definition | Taxonomy |
|---|---|---|
| Dihydrofolate synthase/folylpolyglutamate synthase | A dihydrofolate synthase/folylpolyglutamate synthase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P08192] | Escherichia coli K-12 |
| Folylpolyglutamate synthase, mitochondrial | A folylpolyglutamate synthase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q05932] | Homo sapiens (human) |
| Folylpolyglutamate synthase, mitochondrial | A folylpolyglutamate synthase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q05932] | Homo sapiens (human) |
Compounds (9)
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 3'-amino-2',3'-dideoxythymidine | |||
| methotrexate | dicarboxylic acid; monocarboxylic acid amide; pteridines | abortifacient; antimetabolite; antineoplastic agent; antirheumatic drug; dermatologic drug; DNA synthesis inhibitor; EC 1.5.1.3 (dihydrofolate reductase) inhibitor; immunosuppressive agent | |
| aminopterin | Aminopterin: A folic acid derivative used as a rodenticide that has been shown to be teratogenic. | dicarboxylic acid | EC 1.5.1.3 (dihydrofolate reductase) inhibitor; mutagen |
| dihydrofolate | dihydrofolic acid : A folic acid derivative acted upon by dihydrofolate reductase to produce tetrahydrofolic acid. It interacts with bacteria during cell division and is targeted by various drugs to prevent nucleic acid synthesis. | dihydrofolic acids | Escherichia coli metabolite; mouse metabolite |
| folic acid | folcysteine: used to promote fertility in chickens vitamin B9 : Any B-vitamin that exhibits biological activity against vitamin B9 deficiency. Vitamin B9 refers to the many forms of folic acid and its derivatives, including tetrahydrofolic acid (the active form), methyltetrahydrofolate (the primary form found in blood), methenyltetrahydrofolate, folinic acid amongst others. They are present in abundance in green leafy vegetables, citrus fruits, and animal products. Lack of vitamin B9 leads to anemia, a condition in which the body cannot produce sufficient number of red blood cells. Symptoms of vitamin B9 deficiency include fatigue, muscle weakness, and pale skin. | folic acids; N-acyl-amino acid | human metabolite; mouse metabolite; nutrient |
| n-(4(n-((2-amino-4-hydroxy-6-quinazolinyl)methyl)prop-2-ynylamino)benzoyl)-l-glutamic acid | |||
| 1843u89 | 1843U89: structure given in first source; a folate analog | ||
| 5,11-methenyltetrahydrohomofolate | |||
| 5,6,7,8-tetrahydrofolic acid | tetrahydrofolate : A folate obtained by deprotonation of any tetrahydrofolic acid. tetrahydrofolic acid : A group of heterocyclic compounds based on the 5,6,7,8-tetrahydropteroic acid skeleton conjugated with one or more L-glutamic acid units. | tetrahydrofolic acid | Saccharomyces cerevisiae metabolite |