Coenzyme A biosynthesis begins with pantothenate, a vitamin. In the first step of the pathway, ATP phosphorylates pantothenate to yield the low-energy phosphate ester of 4'-phosphopantothenate and ADP (Figure 14-21). This reaction, which proceeds with the loss of a high-energy bond, is exergonic and unidirectional (PRINCIPLE 2 oF BloENER- GETICs). 4'-Phosphopantothenate reacts with cysteine to form the amide derivative in 4'-phosphopantothenoylcysteine. That CTP is the energy donor in this reaction makes it unusual The carboxyl group is most likely activated as the energy-rich acylphosphate before amide formation. This reaction, which proceeds with the loss of a high-energy bond, is exergonic. The subsequent decarboxylation that yields 4'-phosphopantetheine is also exergonic (PRINCIPLE 6 OF BIOENERGETICs). ATP then serves as an activated adenylyl donor to yield dephospho-CoA and PPi There is retention of the energy-rich simple-acid anhydride bond in dephospho-CoA, and this reaction is functionally isoergonic (PRINCIPLE 1 or BIOENERGETICs). The hydrolysis of PPI thus plays an important thermodynamic role (PRINCIPLE 5 oF BIOENERGETICS) in promoting the forward reaction.