Biochemistry - The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Biosynthesis; how new molecules are formed
Utilization of ATP energy
Group activation

Let us consider The formation of an ester (or amide) from a free carboxylic acid and an alcohol (or amine) with the elimination of a Water molecule [Equation (11-1)].

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These reactions are thermodynamically unfavorable and, depending on the conditions and The Structure of the reacting compounds, are characterized by ∆G' values (at pH 7) ranging from +10 to 30 kJ∙mol. Organic chemists have long known that reactions of this type can be accelerated by carefully removing the water formed from the reaction mixture. However, a more effective approach is to "activate" the carboxylic acid by converting it into an acyl chloride or simply an anhydride

Nucleophilic attack on the carbonyl group in such compounds leads to the displacement of a good leaving group, Cl^- or R—СОО^-. Nature has adopted precisely this pathway, generating derivatives such as acyl phosphate or acyl-CoA from carboxylic acids (Ch. 3, Sec. B; Ch. 7, Sec. E; Table 11-1).

Table 11-1. "Activated" Groups Used in Biosynthesis

The advantages of these activated acyl derivatives in biosynthetic reactions are evident from the data presented in Chapter 7 (Section E) and Table 8-1. Simultaneously with The conversion of a carboxylic acid into an "active acyl," the activation of other groups may occur. The "high-energy phosphates" themselves can be regarded as active phosphoryl compounds. Sulfate is converted into a phosphosulfate anhydride derivative of active sulfuryl. Sugars are transformed into compounds analogous to glucose-1-phosphate or sucrose, containing active glycosyl groups. Although the group-transfer potentials of these compounds are seemingly not as high as that of the ATP phosphate group, they are sufficient to render glucose-1-phosphate and sucrose effective glycosylating agents. Table 11-1 lists some of the most important activated groups.

Group activation typically occurs at the expense of The energy released during the Cleavage of a phosphate group from ATP. This was discussed, in particular, in Chapter 7 (Section E), which highlighted The Central Role of Acyl phosphates in METABOLISM—a fact confirmed by the presence of both an activatable acyl group and an activatable phosphate group:

The high group-transfer potential can be preserved in subsequent reactions by either one group or the other, but not by both simultaneously. Thus, Substitution at the Phosphorus Atom by the ADP oxygen will lead to the regeneration of ATP, whereas carbon attack by an —SH group will yield a thioester. Several Other Compounds listed in Table 11-1 can also undergo cleavage via two pathways to yield different activated groups, such as phosphosulfate anhydride, enol phosphate, and carbamoyl phosphate. Most likely, the ATP cleavage process can be coupled with the synthesis of activated groups only through the formation of intermediate compounds of this type. The Significance of such common intermediates in ATP synthesis via substrate-level phosphorylation has been discussed above (Ch. 8, Sec. 3.5).