Nitric Oxide inhibits Methionine Synthase

An old study, that shows Nitric Oxide inhibits methionine synthase:

We now show spectroscopically that NO reacts with all three valency states of cobalamin and that NO’s inhibition of methionine synthase activity most likely involves its reaction with monovalent cobalamin.

By following incorporation of the methyl moiety of ^14Cmethyltetrahydrofolic acid into protein, we show that NO inhibits methionine synthase activity in vivo, in cultured mammalian cells.

The inhibition of methionine synthase activity disrupted carbon flow through the folate pathway as measured by decreased incorporation of ^14Cformate into methionine, serine, and purine nucleotides." (R1)

Highlights

• NO Decreases Rates of Methionine and Serine Synthesis in Cultured Mammalian Cells
• NO Decreases Rates of de Novo Purine Nucleotide Synthesis in Cultured Mammalian Cells
• Homocysteine Diminishes NO’s Inhibition of de Novo Purine Nucleotide Synthesis
• Physiologically Produced NO Decreases Rates of Methionine, Serine, and de Novo Purine Synthesis in Co-culture Experiments
• NAME (NOS inhibitor) Increases Rates of Methionine, Serine, and de Novo Purine Nucleotide Synthesis

Thus, homocysteine specifically diminished the effect of NO as an inhibitor of purine nucleotide synthesis, presumably by providing substrate and increasing the rate of the methionine synthase reaction. (R1)