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tetrahydrofolylpolyglutamate biosynthetic process

Definition

Target type: biologicalprocess

The chemical reactions and pathways resulting in the formation of tetrahydrofolylpolyglutamate, a folate derivative comprising tetrahydrofolate attached to a chain of glutamate residues. [GOC:ai]

Tetrahydrofolylpolyglutamate (THFPG) biosynthesis is a critical metabolic pathway that generates coenzymes essential for various cellular processes, including nucleotide biosynthesis, amino acid metabolism, and the synthesis of specific lipids. The process involves the sequential addition of glutamate residues to tetrahydrofolate (THF) through the action of folylpolyglutamate synthetase (FPGS). THF serves as a carrier of one-carbon units, which are required for a multitude of metabolic reactions.

The first step in THFPG biosynthesis involves the binding of THF to FPGS, followed by the activation of glutamate by ATP to form γ-glutamyl phosphate. This activated glutamate moiety is then transferred to the γ-carboxyl group of THF, forming THF monoglutamate. Subsequent additions of glutamate residues occur through a similar mechanism, ultimately generating THFPG with varying numbers of glutamate residues.

The number of glutamate residues in THFPG varies depending on the organism and tissue type, typically ranging from 1 to 7. This variation is crucial for the functional activity of THFPG, as the increased polyglutamylation enhances its affinity for specific enzymes involved in folate-dependent metabolic reactions.

THFPG biosynthesis is tightly regulated, ensuring an appropriate balance between the synthesis and degradation of these coenzymes. The process is influenced by factors such as dietary folate intake, cellular metabolic demands, and the availability of essential cofactors.

In summary, THFPG biosynthesis is a complex, essential metabolic pathway that involves the sequential addition of glutamate residues to THF, generating coenzymes critical for various cellular functions. The process is tightly regulated, ensuring an appropriate balance of these crucial metabolites.'
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Proteins (3)

ProteinDefinitionTaxonomy
Dihydrofolate synthase/folylpolyglutamate synthaseA dihydrofolate synthase/folylpolyglutamate synthase that is encoded in the genome of Escherichia coli K-12. [PRO:DNx, UniProtKB:P08192]Escherichia coli K-12
Dihydrofolate synthase/folylpolyglutamate synthaseA 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, mitochondrialA folylpolyglutamate synthase, mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q05932]Homo sapiens (human)

Compounds (9)

CompoundDefinitionClassesRoles
3'-amino-2',3'-dideoxythymidine
methotrexatedicarboxylic 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
aminopterinAminopterin: A folic acid derivative used as a rodenticide that has been shown to be teratogenic.dicarboxylic acidEC 1.5.1.3 (dihydrofolate reductase) inhibitor;
mutagen
dihydrofolatedihydrofolic 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 acidsEscherichia coli metabolite;
mouse metabolite
folic acidfolcysteine: 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
1843u891843U89: structure given in first source; a folate analog
5,11-methenyltetrahydrohomofolate
5,6,7,8-tetrahydrofolic acidtetrahydrofolate : 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 acidSaccharomyces cerevisiae metabolite
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