Methenyltetrahydrofolate synthetase is a high-affinity catecholamine-binding protein

Anguera, Montserrat C.

doi:10.1016/j.abb.2006.09.008

Cited by 5 publications

(3 citation statements)

References 33 publications

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“…Glycerol aldehyde phosphate dehydrogenase (GAPDH) was used as a loading control. (A) Three samples per genotype and diet were run for colon, and this blot includes mouse recombinant MTHFS (purified as described previously Anguera and Stover, 2006 ). (B) Two samples were run per genotype per diet for liver, kidney and brain.…”

Section: Resultsmentioning

confidence: 99%

Mthfs is an Essential Gene in Mice and a Component of the Purinosome

Field¹,

Anderson²,

Stover³

2011

Front. Gene.

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Tetrahydrofolates (THF) are a family of cofactors that function as one-carbon donors in folate-dependent one-carbon metabolism, a metabolic network required for the de novo synthesis of purines, thymidylate, and for the remethylation of homocysteine to methionine in the cytoplasm. 5-FormylTHF is not a cofactor in one-carbon metabolism, but serves as a storage form of THF cofactors. 5-formylTHF is mobilized back into the THF cofactor pool by methenyltetrahydrofolate synthetase (MTHFS), which catalyzes the irreversible and ATP-dependent conversion 5-formyltetrahydrofolate to 5,10-methenyltetrahydrofolate. Mthfs is not an essential gene in Arabidopsis, but MTHFS expression is elevated in animal tumors, enhances de novo purine synthesis, confers partial resistance to antifolate purine synthesis inhibitors and increases rates of folate catabolism in mammalian cell cultures. However, the mechanisms underlying these effects of MTHFS expression have yet to be established. The purpose of this study was to investigate the role and essentiality of MTHFS in mice. Mthfs was disrupted through the insertion of a gene trap vector between exons 1 and 2. Mthfsgt/+ mice were fertile and viable. No Mthfsgt/gt embryos were recovered from Mthfsgt/+ intercrosses, indicating Mthfs is an essential gene in mice. Tissue MTHFS protein levels are decreased in both Mthfsgt/+ and Mthfs+/+ mice placed on a folate and choline deficient diet, and mouse embryonic fibroblasts from Mthfsgt/+ embryos exhibit decreased capacity for de novo purine synthesis without impairment in de novo thymidylate synthesis. MTHFS was shown to co-localize with two enzymes of the de novo purine synthesis pathway in HeLa cells in a cell cycle-dependent manner, and to be modified by the small ubiquitin-like modifier (SUMO) protein. Mutation of the consensus SUMO modification sites on MTHFS eliminated co-localization of MTHFS with the de novo purine biosynthesis pathway under purine-deficient conditions. The results from this study indicate that MTHFS enhances purine biosynthesis by delivering 10-formylTHF to the purinosome in a SUMO-dependent fashion.

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Section: Resultsmentioning

confidence: 99%

Mthfs is an Essential Gene in Mice and a Component of the Purinosome

Field¹,

Anderson²,

Stover³

2011

Front. Gene.

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“…Finally, besides their important role in the clearance of indoleamines, neuroprotection, and cell division, information accumulates suggesting the end products, NAS and NAD, may modulate enzyme activities including tryptophan hydroxylase and dopamine hydroxylase , thus suggesting they might be part of a feedback loop within the monoamines metabolic pathways. NAD also stimulates methenyltetrahydrofolate synthase, which is important in the folate metabolism ). Interestingly, studies in the mammalian retina indicate that methyltetrahydrofolate can be excited by light and is one cofactor of cryptochromes, which are part of the molecular clock machinery .…”

Section: Discussionmentioning

confidence: 99%

Subfunctionalization of arylalkylamine N‐acetyltransferases in the sea bass Dicentrarchus labrax: two‐ones for one two

Paulin

Cazaméa-Catalan

Zilberman-Peled

et al. 2015

Journal of Pineal Research

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Melatonin is an important component of the vertebrates circadian system, synthetized from serotonin by the successive action of the arylalkylamine N-acetyltransferase (Aanat: serotonin→N-acetylserotonin) and acetylserotonin-O-methyltransferase (Asmt: N-acetylserotonin→melatonin). Aanat is responsible for the daily rhythm in melatonin production. Teleost fish are unique because they express two Aanat genes, aanat1 and aanat2, mainly expressed in the retina and pineal gland, respectively. In silico analysis indicated that the teleost-specific whole-genome duplication generated Aanat1 duplicates (aanat1a and aanat1b); some fish express both of them, while others express either one of the isoforms. Here, we bring the first information on the structure, function, and distribution of Aanat1a and Aanat1b in a teleost, the sea bass Dicentrarchus labrax. Aanat1a and Aanat1b displayed a wide and distinct distribution in the nervous system and peripheral tissues, while Aanat2 appeared as a pineal enzyme. Co-expression of Aanats with asmt was found in the pineal gland and the three retinal nuclear layers. Enzyme kinetics indicated subtle differences in the affinity and catalytic efficiency of Aanat1a and Aanat1b for indolethylamines and phenylethylamines, respectively. Our data are consistent with the idea that Aanat2 is a pineal enzyme involved in melatonin production, while Aanat1 enzymes have a broader range of functions including melatonin synthesis in the retina, and catabolism of serotonin and dopamine in the retina and other tissues. The data are discussed in light of the recently uncovered roles of N-acetylserotonin and N-acetyldopamine as antioxidants, neuroprotectants, and modulators of cell proliferation and enzyme activities.

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“…6 ). This effect was specific to oxNADA and was not observed with other catecholamines ( 158 ). oxNADA does not seem to inhibit MTHFS catalytic activity and it remains to be seen how this association modulates folate levels in cells and in vivo .…”

Section: Regulation Of One-carbon Metabolism By Feedback Loops At The...mentioning

confidence: 84%

Regulatory mechanisms of one-carbon metabolism enzymes

Petrova,

Maynard,

Wang

et al. 2023

Journal of Biological Chemistry

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Methenyltetrahydrofolate synthetase is a high-affinity catecholamine-binding protein

Cited by 5 publications

References 33 publications

Mthfs is an Essential Gene in Mice and a Component of the Purinosome

Mthfs is an Essential Gene in Mice and a Component of the Purinosome

Subfunctionalization of arylalkylamine N‐acetyltransferases in the sea bass Dicentrarchus labrax: two‐ones for one two

Regulatory mechanisms of one-carbon metabolism enzymes

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