Other folate-dependent enzymes

"Other folate-dependent enzymes" refers to a heterogeneous group of enzymes within the one-carbon metabolism network that utilize folate derivatives as essential cofactors, excluding the primary targets dihydrofolate reductase (DHFR) and thymidylate synthase (TS) [PMID: 11560818]. This category encompasses enzymes such as glycinamide ribonucleotide transformylase (GART), aminoimidazole carboxamide ribonucleotide transformylase (AICARFT), and methylenetetrahydrofolate dehydrogenase (MTHFD), which are essential for the de novo synthesis of purine nucleotides [PMID: 10485309]. These enzymes facilitate the transfer of one-carbon units required for the biosynthesis of DNA, RNA, and amino acids like methionine and serine [PMID: 23430461]. In clinical oncology, multi-targeted antifolates like pemetrexed are designed to inhibit several of these enzymes simultaneously, thereby disrupting cellular proliferation more effectively than single-target agents [PMID: 12154053]. Because these metabolic pathways are fundamental to all rapidly dividing cells, pharmacological inhibition often leads to systemic toxicities such as myelosuppression, mucositis, and gastrointestinal distress [PMID: 15534355]. Consequently, these enzymes represent a significant area of research for developing more selective antimetabolites and understanding the metabolic dependencies of various cancers and autoimmune conditions.

Other names

Folate-metabolizing enzymesOne-carbon metabolism enzymesFolate-dependent transformylasesNon-DHFR folate enzymes

Inhibition of enzymes involved in the transfer of one-carbon units, leading to the disruption of de novo purine and pyrimidine synthesis and subsequent inhibition of DNA and RNA production.