Enzymatic Acetyl Transfer Reaction

Several TIs have been found to correlate with the enzymatic acetyl transfer reaction, as shown by the following equations  

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Coenzyme A. CoA. C HjjNjO PjS mol wt 767.55. C 32.86%, H 4.73%, N 12.78%, O 33.35%, P 12.11%, S 4.18%, A co-factor in enzymatic acetyl transfer reactions. The molecule is built up from pantetheine [Lactobacillus bulgaricus factor consisting of pantothenic acid and cyste-amine (thioethylamine 0-mercaptoethylamine decarboxyl -ated cysteine)], adenosine, and phosphoric acid. Iscln from... 

C21H35N7O15P3S 767.54 Constit. of many microorganisms. A cofactor in enzymatic acetyl transfer reactions. 5-Acyl derivs (see below) are biochemically important in acyl transfer... 

When we examined molecular models of this system we discovered that the tetrahedral intermediate for acetyl transfer has a geometry such that the f-butylphenyl group is pulled somewhat out of the cavity. That is, the substrate is bound nicely but the transition state is bound more poorly, at least judged from models. This is the opposite of the situation needed to achieve maximum acceleration. Thus, we set out to improve this kind of reaction in two directions. The goal here was to discover if we could indeed produce accelerations that were of enzymatic magnitude by careful attention to geometrical relationships between the lock and the key. 

An enzymatic reaction intermediate formed by phospho-ryl transfer to a carboxyl group on an enzyme. Acyl-phosphates are structurally analogous to acid anhydrides (R—CO —O —CO—R ), and they are thermodynamically less stable than either of the two phosphoanhydride bonds in ATP. This is evident by the fact that the acetate kinase reaction (ADP + acetyl-phosphate = ATP + acetate) favors ATP formation with an equilibrium constant of about 3,000. Acetyl-phosphate can be chemically synthesized by reacting orthophosphate with acetic anhydride. 

Fatty acid synthesis begins when the substrates, acetyl-CoA and malonyl-CoA, are transferred onto the protein by malonyl-CoA acetyl-CoA-ACP transacylase (MAT, steps 1 and 2 in fig. 18.12a). The numbers in parentheses below the abbreviation of the enzyme in this figure refer to the reactions shown in fig. 18.12. (Whereas E. coli has separate enzymes that catalyze the transfer of acetyl- and malonyl-CoA to ACP, both reactions are catalyzed by the same enzymatic activity (MAT) on the animal fatty acid synthase.) Subsequently, /3-ketobutyryl-ACP and CO2 are formed in a condensation reaction catalyzed by /3-ketoacyl-ACP synthase (KS, step 3 in fig. 18.12a). 

Of these reactions acetylation is the most extensive but the extent to which it occurs varies with the sulfonamide, species and individual. The acetylation involves the enzymatic transfer of the acetyl group from acetyl coenzyme A by acetyl-transferase, and although, usually considered to occur in hepatic tissue, has been shown to take place in the reticulo-endothelial cells (127). 

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