Chapter 4 - The Enzymatic Activities of Sirtuins

Abstract

Sirtuins are a class of nicotinamide adenine dinucleotide-consuming enzymes that are implicated in numerous biological pathways and are considered a promising target for treating human diseases. There are seven sirtuins in mammals, SIRT1–7. This chapter focuses on the enzymology of sirtuins and will discuss the different enzymatic activities that have been reported for sirtuins, the reaction mechanisms, and the physiological relevance. Of particular importance is the recent discovery that sirtuins can remove a variety of different acyl lysine modifications from proteins. Some sirtuins can recognize structurally very different acyl lysine modifications. The factors that determine substrate specificity are summarized. The competition between different acyl lysine substrates for the same sirtuin may produce interesting physiological and pharmacological effects, which are also briefly discussed.