Nucleophilic acyl substitution thioesters

Step 6 begins with a nucleophilic addition reaction to the aldehyde group of glyceraldehyde 3-phosphate by a thiol group of an enzyme to form a hemithioacetal, which is oxidized by NAD+ to an acyl thioester. Nucleophilic acyl substitution by phosphate yields the product 1,3-bisphosphoglycerate. 

Thioesters undergo the same kinds of reactions as esters and by similar mechanisms Nucleophilic acyl substitution of a thioester gives a thiol along with the product of acyl transfer For example... 

As we saw m Chapter 20 thioesters are more reactive than ordinary esters toward nucleophilic acyl substitution They also contain a greater proportion of enol at equilib rmm Both properties are apparent m the properties of acetyl coenzyme A In some reactions it is the carbonyl group of acetyl coenzyme A that reacts m others it is the a carbon atom... 

Formation of malonyl coenzyme A is followed by a nucleophilic acyl substitution which transfers the malonyl group to the acyl carrier protein as a thioester... 

The first example in Table 20.2 introduces a new aspect of nucleophilic acyl substitution that applies not only to acid anhydrides but also to acyl chlorides, thioesters, esters, and amides. Nucleophilic acyl substitutions can be catalyzed by acids. 

Figure 21.9 Formation of the thioester acetyl CoA by nucleophilic acyl substitution reaction of coenzyme A (CoA with acetyl adenylate.

Another example of a nucleophilic acyl substitution reaction, this one a substitution by hydride inn to effect partial reduction of a thioester to an aldehyde, occurs in the biosynthesis of mevaldehyde, an intermediate in terpenoid... 

Step 2, another priming reaction, involves a further exchange of thioester linkages by another nucleophilic acyl substitution and results in covalent bonding of the acetyl group to a cysteine residue in the synthase complex that will catalyze the upcoming condensation step. 

Step 5 of Figure 29.11 Acyl Transfer Acetyl dihydrolipoamide. a thioester, undergoes a nucleophilic acyl substitution reaction with coen/.yrne A to yield acetyl CoA plus dihydrolipoamide. The dihydrolipoamide is then oxidized back... 

Thioesters are more reactive toward nucleophilic acyl substitution than normal esters, but less reactive than acid chlorides and anhydrides. If we add thioesters to the order of reactivity, we have the following sequence ... 

Ttie thioester group of citryl CoA is hydrolyzed by a typical nucleophilic acyl substitution reaction to produce citrate plus coenzyme A. 

Steps 1-2 of Figure 29.5 Acyl Transfers The starting material for fatty-acid synthesis is the thioester acetyl CoA, the ultimate product of carbohydrate break-dowm, as wee ll sec in Section 29.6. The synthetic pathway begins with several primifiy reactions, w hich transport acetyl CoA and convert it into more reactive species. The first priming reaction is a nucleophilic acyl substitution reaction that converts acetyl CoA into acetyl ACP (acyl carrier protein). The reaction is catalyzed by ACP transacyJase. 

The carbon-sulfur bond of a thioester is rather long—typically on the order of 180 pm—and delocalization of the sulfur lone-pair electrons into the rr orbital of the carbonyl group is not as effective as in esters. Nucleophilic acyl substitution reactions of thioesters occur faster than those of simple esters. A number of important biological processes involve thioesters several of these are described in Chapter 26. 

Thioesters are the most common forms of activated carboxylic acids in a cell. Although thioesters hydrolyze at about the same rate as oxygen esters, they are much more reactive than oxygen esters toward attack by nitrogen and carbon nucleophiles. This allows a thioester to survive in the aqueous environment of the cell—without being hydrolyzed—waiting to be a substrate in a nucleophilic acyl substitution reaction. 

The vitamin precursor of CoASH is pantothenate. We have seen that CoASH is used in biological systems to activate carboxylic acids by converting them into thioesters, which are much more reactive toward nucleophilic acyl substitution reac-... 

If the carboxylate ion attacks the y-phosphorus of ATP, an acyl phosphate is formed. The acyl phosphate then reacts with the thiol in a nucleophilic acyl substitution reaction (Section 17.5) to form the thioester. 

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