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In the cytosol, the trifunctional enzyme MTHFD1 catalyzes dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase reactions to interconvert these THF intermediates and formate, whereas in mitochondria,these interconversions are carried out by MTHFD2/MTHFD2L (dehydrogenase/cyclohydrolase) and MTHFD1L (formyltetrahydrofolate synthetase), respectively (Fig