Allosteric inhibition of MTHFR prevents futile SAM cycling and maintains nucleotide pools in one-carbon metabolism
Muskan Bhatia, Jyotika Thakur, Shradha Suyal, Ruchika Annie O’Niel, Rahul Chakraborty, Shalini Pradhan, Monika Sharma, Shantanu Sengupta, Sunil Laxman, Shyam Kumar Masakapalli, Anand Bachhawat
Abstract
THF) to form methionine. This reaction also drives SAM formation and further depletes ATP reserves. SAM was then cycled back to methionine, leading to futile cycles of SAM synthesis and recycling and explaining the necessity for MTHFR to be regulated by SAM. The study has yielded valuable new insights into the regulation of one-carbon metabolism, and the mutants appear as powerful new tools to further dissect out the intersection of one-carbon metabolism with various pathways both in yeasts and in humans.
Topics & Concepts
TransmethylationMethylenetetrahydrofolate reductaseTranssulfurationMethionineBiochemistryMethionine synthaseMetabolismHomocysteineMethionine AdenosyltransferaseAllosteric regulationCystathionine beta synthaseChemistryBiologyEnzymeAmino acidGeneGenotypeFolate and B Vitamins ResearchRNA modifications and cancerPolyamine Metabolism and Applications