How Cells Activate Carboxylic Acids

The synthesis of compounds by a hving organism is called biosynthesis. Acyl chlorides and acid anhydrides are too reactive to be used as reagents in cells. Cells live in a predominantly aqueous enviromnent, and acyl halides and acid anhydrides are rapidly hydrolyzed in water. So cells must activate carboxylic acids in a different way. 

When phosphoric acid is heated with P2O5, it loses water, forming a phosphoanhydride called pyrophosphoric acid. Its name comes from pyr, the Greek word for fire, since pyrophosphoric acid is prepared by fire —that is, by heating. Triphosphoric acid and higher polyphosphoric acids are also formed. 

One way cells can activate a carboxylic acid is to use adenosine triphosphate (ATP) to convert the carboxylic acid into an acyl phosphate or an acyl adenylate—carbonyl compounds with good leaving groups. ATP is an ester of triphosphoric acid. Its sttucture is shown here, both in its entirety and with Ad in place of the adenosyl group. 

Acyl phosphates and acyl adenylates are mixed anhydrides of a carboxylic acid and phosphoric acid. 

An acyl phosphate is formed by nucleophilic attack of a carboxylate ion on the y-phosphorus (the phosphorus farthest away from the adenosyl group) of ATP. Attack of the nucleophile breaks the phosphoanhydride bond (rather than the tt bond), so an intermediate is not formed. Essentially, it is an Sn2 reaction with an adenosine diphosphate leaving group. 

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