Acetyl group, donor transfer

Thioesters and oxoesters are similar in their rates of nucleophilic acyl substitution, except with amine nucleophiles for which thioesters are much more reactive. Many biological reactions involve nucleophilic acyl substitutions referred to as acyl transfer reactions. The thioester acetyl coenzyme A is an acetyl group donor to alcohols, amines, and assorted other biological nucleophiles. 

Effective charge data show that the equilibrium for transfer of an acetyl group from a donor to aryloxide ions has a Peq of +1.7 compared with that of the protonation of aryloxide ions (P = +1). 

The replacement of the N-acetyl group of the N-acetylglucosaniine unit is widely tolerated (Table 9). Especially striking is again the selective fucosylation of the glycuronamide derivatives (entries 11-15). Heterocyclic substituents on the acceptor apparently do not affect the enzyme either (entries 8-10). Nonnatural fucose donors are also recognized by FucT III and transferred in the expected way to form Lewis trisaccharides or sialyl-Lewis tetrasaccharides, respectively (see Fig. 14). 

Acetyl CoA carries the acetyl group from glycolysis or fj-oxidation of a fatty acid to an intermediate of the citric acid cycle. This reaction is an example of an acyl group transfer reaction. In this case, the acyl group donor is a thioester— acetyl CoA. The acyl group being transferred is the acetyl group, which is transferred to the carbonyl carbon of oxaloacetate. This reaction is shown here ... 

Acetyl-CoA carboxylase (ACC) catalyzes the first committed step in long-chain fatty acid biosynthesis (see Chapter 7.11). The overall reaction is catalyzed in two sequential reactions (Scheme 3). First, the biotin carboxylase domain catalyzes the ATP-dependent carboxylation of biotin (which is attached to a carrier protein) using bicarbonate as a CO2 donor. In the second reaction, the carboxyl group is transferred from biotin to acetyl-CoA to form malonyl-CoA. In mammals, both reactions are catalyzed by a single protein, but in Escherichia coli and other bacteria, the activity is catalyzed by two separate proteins, a biotin carboxylase and a carboxytransferase. Due to its role in fatty acid synthesis, inhibitors of the overall ACC reaction are proposed to be useful as antiobesity drugs in mammals as well as novel antibiotics against bacteria. 

There is no evidence to indicate that such acetyl groups are added to neutral sugars or uronic acids before polymer assembly. The sugar nucleotide donors, such as UDPXyl, are all derivatives of simple sugars synthetic nucleotides based upon substituted sugars have generally been found to be totally inactive. Hence acetyl transfer probably occurs after glycosyl transfer, but quite possibly before the polymer is complete. How many acetyltransferases exist is unknown. 

At present, acetyl-CoA is regarded as a pivotal point in the transfer of acetyl groups. It can arise from many donor systems, including pyruvate from carbohydrate metabolism and acetate from fatty acids. 

The enzymic transfer of 0-acetyl groups to positions 4, 7, 8, and 9 has been detected in bovine and equine submandibular glands (see Schauer 1978 b for a review). The acetyl donor is acetyl coenzyme A (AcCoA), and no other cofactors could be detected. Using radiolabelling techniques it was demonstrated that the spheroplast membranes of Meningococcus group C transfer acetyl groups from AcCoA to sialic acids of the polysaccharide synthesized in vitro (Vann et al. 1978). 

The high level resistance of certain bacteria to Cm is due to the enzyme chloramphenicol acetyltransferase (CAT) which modifies the Cm to a biologically inactive derivative. CAT is an intracellular, trimeric enzyme with an average monomer size of 25 kDa. CAT catalyzes the transfer of an acetyl group from donor acetyl-CoA to the primary (C-3) hydroxyl of Cm, generating chloramphenicol 3-acetate and CoA-SH as products (Fig. 8.7). The acetylated Cm is incapable of binding to bacterial ribosome and is devoid of antimicrobial activity. 

This enzyme primes the cycle with acetylglutamate. Once primed, the acetylor-nithine formed functions as the acetyl donor to complete the cycle. The transfer of the acetyl group from acetylomithine is carried out by the second enzyme, A -acetyl-L-omithineiL-glutamate iV-acetyltransferase (EC 2.3.1.35). 

Fig. 11. Active sites and reactions of the bifunctional CODH/ACS. For synthesis of acetyl-CoA, two electrons are transferred from external electron donors to Cluster B of the CODH subunit. Electrons are relayed to Cluster C which reduces CO2 to CO. The CO is proposed to be channeled to Cluster A of the ACS subunit to form a metal-CO adduct that combines with the methyl group of the CFeSP and CoA to form acetyl-CoA. For utilization of acetyl-CoA, these reactions are reversed. The abbreviations are CODH, CO dehydrogenase ACS, acetyl-CoA synthase CFeSP, the corrinoid iron-sulfur protein CoA, Coenzyme A.

---