Possible mechanisms of inhibition and activation of rat N-acetyltransferase (EC 2.3.1.5.) by cations.

The possible mechanisms of inhibition and activation of various cations on rat pineal N-acetyltransferase (NAT) were elucidated. Copper was found to be a partial mixed noncompetitive inhibitor of NAT with respect to both substrates and this inhibition can be considered to result primarily from impairment of tryptamine (serotonin) binding to the enzyme. Both calcium and magnesium were found to activate NAT by a similar mechanism, with calcium being more effective than magnesium. It appears that the activation results from cation binding to the enzyme causing an increased affinity of tryptamine (serotonin) for binding to NAT and therefore enhancing catalytic activity. The monovalent cations, potassium and sodium, activated NAT by a similar mechanism which differed from the caused by the divalent cations. It can be suggested that tryptamine (serotonin) binds to the enzyme followed by the monovalent cation which enhances binding of the acetyl donor and thereby promotes catalysis. At high potassium or sodium concentration the affinity of acetyl coenzyme A for NAT begins to decrease suggesting that excess monovalent cations can be inhibitory and may represent an endogenous regulatory mechanism controlling in vivo NAT activity. It is possible that certain cations may be involved in regulation of melatonin synthesis although the physiological significance of such modulation remains unknown.