Disease relevance of MTHFS

• Escherichia coli BL21(DE3), transfected with pET11c plasmids containing an open reading frame encoding MTHFS, showed a 100-fold increase in MTHFS activity in bacterial extracts after IPTG induction [1].
• The regulation and metabolic role of MTHFS in one-carbon metabolism was investigated in vitro and in human neuroblastoma cells [2].
• Mycoplasma pneumoniae 5,10-methenyltetrahydrofolate synthetase [MTHFS; also known as 5-formyltetrahydrofolate cycloligase; Enzyme Commission (EC) 6.3.3.2] belongs to a large cycloligase protein family with 97 sequence homologues from bacteria to human [3].
• Studies using purified mitochondrial MTHFS from CA46 human Burkitt lymphoma cells reveal that mitochondrial MTHFS behaves kinetically like the cytoplasmic enzyme with Km values of 4.7, 0.8 and 22 microM respectively for (6R,S)-5-formyltetrahydrofolate monoglutamate, (6S)-5-formyltetrahydrofolate pentaglutamate and ATP [4].

High impact information on MTHFS

• The sequestration of 10-formylTHF by MTHFS may explain why de novo purine biosynthesis is protected from common disruptions in the folate-dependent one-carbon network [2].
• Methenyltetrahydrofolate synthetase (MTHFS) is the only enzyme known to metabolize 5-formyltetrahydrofolate and catalyzes the conversion of 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate [5].
• Purified recombinant mouse MTHFS and rabbit liver MTHFS proteins were shown to bind oxidized N-acetyldopamine (NADA) tightly [6].
• We present evidence for the presence of the folate metabolism enzyme methenyltetrahydrofolate synthetase (MTHFS) in mitochondria [4].
• Intracellular tetrahydrofolate metabolism is highly compartmentalized and mitochondrial MTHFS activity is necessary for the entry of mitochondrial 5-formyltetrahydrofolate into the mitochondrial folate pool [4].

Chemical compound and disease context of MTHFS

• In order to address the function of 5-formyltetrahydrofolate in mammalian cells, intracellular 5-formyltetrahydrofolate levels were depleted in human 5Y neuroblastoma by overexpressing the human cDNA encoding MTHFS (5YMTHFS cells) [5].

Anatomical context of MTHFS

• MTHFS activity was identified in the matrix of mitochondria purified from human liver biopsies [4].

Associations of MTHFS with chemical compounds

• Methenyltetrahydrofolate synthetase (MTHFS) catalyses the obligatory initial metabolic step in the intracellular conversion of 5-formyltetrahydrofolate to other reduced folates [1].

Analytical, diagnostic and therapeutic context of MTHFS

• Northern blot studies of human tissues determined that the MTHFS mRNA was expressed preferentially in the liver and Southern blot analysis of human genomic DNA suggested the presence of a single-copy gene [1].

References