Some Biological Carbonyl Condensation Reactions

Aldol reactions occur in many biological pathways, but are particularly important in carbohydrate metabolism, where enzymes called aliiolases catalyze the addition of a ketone enolate ion to an aldehyde.. Aldolases occur in all organisms and are of two types. Type I aldolases occur primarily in animals and higher plants type II aldolases occur primarily in fungi and bacteria. Both types catalyze the same kind of reaction, but type 1 aldolases operate place through an enamine, while type II aldolases require a metal ion (usually Zn- ) as Lewis acid and operate through an enolate ion. 

Mixed Claisen condensations (Section 23.8) also occur frequently in living organisms, particularly in the pathway for fatty-acid biosynthesis that we ll discuss in Section 29.4. Butyryl synthase, for instance, reacts with malonyl AGP in a mixed Claisen condensation to give 3-ketohexanoyl AGP. 

Biochemistry is carbonyl chemistry.. Almost all metabolic pathways used by living organisms involve one or more of the four fundamental carbonyl-group reactions we ve seen in Chapters 19 through 23. The digestion and metabolic breakdown of all the major classes of food molecules—fats, carbohydrates, and proteins—take place by nucleophilic addition reactions, nucleophilic acyl substitutions, a substitutions, and carbonyl condensations. Similarly, hormones and other crucial biological molecules are built up from smaller precursors by these same carbonyl-group reactions. 

Take glycolysis, for example, the metabolic pathway by which organisms convert glucose to pyruvate as the first step in e.xtracting energy from carbohydrates. 

You are what you eat. Food molecules are metabolized by pathways that involve the four major carbonyl-group reactions. 

Note that the aldolase-catalyzed reactions are mixed aldol reactions, which take place between two different partners, as opposed to the symmetrical aldol reactions between identical partners usually carried out in the laboratory. Mixed aldol reactions between different partners often give mixtures of products in the laboratory but are successful in living systems because of the selectivity of the enzyme catalysts. 

Glycolysis is a ten-step process that begins with isomerization of glucose from its cyclic hemiacelal forni to its open-chain aldehyde form—a reverse nucleophilic addition reaction. I he aldehyde then undergoes tautomeriza-tion to yield an enol, which undergoes yet another tautomerization to give the ketone fructose. 

Fructose, a )S-hydroxy ketone, is then cleaved into two three-carbon molecules—one ketone and one aldehyde— by a rev erse aldol reaction. Still further carbojiyi-grou( reactions then occur until pyruvate results. 

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