Contrasting Effects of Temperature on Human Arylamine N-Acetyltransferase and Acetyl Coenzyme A Hydrolase Activities

There are two human arylamine N-acetyltransferases(NAT1 and NAT2) that have evolved separately and differ in their substratespecificity and tissue localization. In addition to its acetyltransferaseactivity, NAT1 can hydrolyze acetyl coenzyme A to coenzyme A in thepresence of folate. Here, we show that NAT1 is rapidly inactivatedat temperatures above 39 & DEG;C whereas NAT2 is more stable. NAT1acetyltransferase activity is also rapidly lost in whole cells ata rate similar to that of recombinant protein, suggesting it is notprotected by intracellular chaperones. By contrast, the hydrolaseactivity of NAT1 is resistant to heat-induced inactivation, in partbecause folate stabilizes the protein. Heat generated by mitochondriafollowing the dissipation of the inner membrane potential was sufficientto inactivate NAT1 in whole cells. Within the physiological rangeof core body temperatures (36.5-37.5 & DEG;C), NAT1 acetyltransferaseactivity decreased by 30% while hydrolase activity increased by >50%.This study demonstrates the thermal regulation of NAT1, but not NAT2,and suggests that NAT1 may switch between an acetyltransferase anda hydrolase within a narrow temperature range in the presence of folate.

Automated summary

There are two human arylamine N-acetyltransferases (NAT1 and NAT2) that differ in their substratespecificity and tissue localization. NAT1 can hydrolyze acetyl coenzyme A to coenzyme A in the presence of folate, and it is rapidly inactivated at temperatures above 39 °C. The acetyltransferase activity of NAT1 is also rapidly lost in whole cells, while the hydrolase activity is resistant to heat-induced inactivation due to the stabilizing effect of folate.