In chapter 11, we learned about the chemistry of aldehydes and ketones. We saw several variations on a single overarching theme – the attack by a nucleophile on the electrophilic carbonyl carbon. In this chapter, we will see many variations of a reaction type known as nucleophilic acyl substitution, the substrates for which are not aldehydes and ketones but carboxylic acid derivatives, such as acyl phosphates, thioesters, esters, and amides. It is difficult to overemphasize how widespread nucleophilic acyl substitution reactions are in biochemical pathways: you will see them again and again when you take a course in biochemistry. As we shall soon see, these reactions are especially important in the metabolism of lipids (fats and oils) and in the formation and breakdown of peptide bonds in proteins.