SAM is unstable at pH 7.5, 37 °C. For extended reactions adding more SAM after 4 hours can improve results. Methylation reactions, however, are also greatly affected by S-adenosylhomocysteine. S-adenosylhomocysteine, the byproduct of the methylation reaction binds more tightly to methylases than does SAM. Inhibition by S-adenosylhomocysteine greatly reduces the reaction rate as time passes. Using more enzyme in shorter reactions may improve methylation.