Methylenetetrahydrofolate dehydrogenase – methenyltetrahydrofolate cyclohydrolase –formyltetrahydrofolate synthetase from porcine liver: evidence to support a common dehydrogenase–cyclohydrolase site

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Abstract
The cyclohydrolase activity of the trifunctional enzyme methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase is inhibited by NADP, a substrate of the dehydrogenase. This uncompetitive inhibition, shown also by 3-aminopyridine adenine dinucleotide phosphate (AADP), indicates formation of dead-end complexes consisting of enzyme-nucleotide-methenyltetrahydrofolate. Chemical modification with diethylpyrocarbonate inactivates the dehydrogenase and cyclohydrolase but not the synthetase. Folate, but neither NADP nor AADP, protects both activities against modification. However, NADP potentiates the protection by folate by decreasing the apparent Kd for that ligand .apprx. 6-fold. Chemical modification with phenylglyoxal also inactivates both the dehydrogenase and cyclohydrolase activities. Neither activity was protected by NADP or folate alone; however, the combination of NADP and folate protected both activities. These results are consistent with a model in which the dehydrogenase and cyclohydrolase activities share a common folate binding site.

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