N-Acetyltransferases

E Wolf, A Vassilev, Y Makmo, A Sail, Y Nakatam, SK Burley. Crystal structure of a GCN5-related N-acetyltransferase Serratia marcescens aminoglycoside 3-N-acetyltransferase. Cell 94 51-61, 1998. 

The metabolism of foreign compounds (xenobiotics) often takes place in two consecutive reactions, classically referred to as phases one and two. Phase I is a functionalization of the lipophilic compound that can be used to attach a conjugate in Phase II. The conjugated product is usually sufficiently water-soluble to be excretable into the urine. The most important biotransformations of Phase I are aromatic and aliphatic hydroxylations catalyzed by cytochromes P450. Other Phase I enzymes are for example epoxide hydrolases or carboxylesterases. Typical Phase II enzymes are UDP-glucuronosyltrans-ferases, sulfotransferases, N-acetyltransferases and methyltransferases e.g. thiopurin S-methyltransferase. 

Protein phosphatase 2C Protein arginine methyltransferase Protein arginine methyltransferase Arylalkylamine N-acetyltransferase SARS Cov 3C-like protease AHAS... 

Iuvone, P. M., Tosini, G., Pozdeyev, N. et al. (2005). Circadian clocks, clock networks, arylalkylamine N-acetyltransferase, and melatonin in the retina. Prog. Retin. Eye Res. 24, 433-56. 

Hein DW, Grant DM, Sim E. Update on consensus arylamine N-acetyltransferase gene nomenclature. Pharmacogenetics 2000 10 1-2. 

Finally, polymorphisms associated with arylamine N-acetyltransferase (NAT2) may result in slow acetylators. The slow-acetylator phenotype is present in 50-70% of the population in Western countries and is associated with several drug-induced side effects. The frequency of the slow-acetylator phenotype rises to 80% in Egyptian and certain Jewish populations however, the frequency drops to 10% or 20% among Japanese and Canadian Eskimos. 

EC2 Transferases methyltransferase, aspartate carbamoyltransferase, etc.) EC2.3 Acvltransferases (amino-acid N-acetyltransferase, ATP citrate synthase, etc.) luciferasa ... 

N-Acetyltransferases catalyze the transfer of an acetyl moiety from coenzyme A (CoASAc) to an acceptor amine as seen in Eq. (10). The nature of the... 

BoukouvalaS, FakisG. Arylamine N-acetyltransferases what we learn from genes and genomes. Drug Metab Rev 2005 37(3) 511-564. 

Grant DM, Blum M, Beer M, et al. Monomorphic and polymorphic human arylamine N-acetyltransferases a comparison of liver isozymes and expressed products of two cloned genes. Mol Pharmacol 1991 39(2) 184-191. 

Zhang N, Liu L, Liu F, et al. NMR-based model reveals the structural determinants of mammalian arylamine N-acetyltransferase substrate specificity. J Mol Biol 2006 363(l) 188-200. 

Windmill KF, Gaedigk A, Hall PM, et al. Localization of N-acetyltransferases NAT1 and NAT2 in human tissues. Toxicol Sci 2000 54(l) 19-29. 

Mammalian HAT enzymes can be divided into subfamilies (Tan, 2001). However, it is currently difficult to classify a protein as a potential HAT enzyme based on its amino acid sequence, since these subfamilies display no obvious similarity in their primary sequence, nor in the size of their HAT domains or the surrounding protein modules (Kuo and Allis, 1998 Marmorstein, 2001). The only region that is partly conserved between HAT subfamilies, either on the amino acid sequence and/or structural level, is a small subdomain first noticed in GCN5-related N-acetyltransferases, which encompasses the coenzyme A (CoA) binding site (Neuwald and Landsman, 1997 Martinez-Balbas et al, 1998 Yan et al, 2000 Marmorstein and Roth, 2001). Four families of mammalian HATs that have been implicated in human disease will be discussed here. 

There is no information regarding the metabolism of 3,3 -dichlorobenzidine in children. However, N-acetylation (as discussed above) in humans is likely done by one of two families of N-acetyltransferases. One of these families, NAT2, is developmentally regulated (Leeder and Kearns 1997). Some enzyme activity can be detected in the fetus by the end of the first trimester. Almost all infants exhibit the slow acetylator phenotype between birth and 2 months of age. The adult phenotype distribution is reached by the age of 4-6 months, whereas adult activity is found by approximately 1-3 years of age. Also, UDP-glucuronosyltransferase, responsible for the formation of glucuronide conjugates, seems to achieve adult activity by 6-18 months of age (Leeder and Kearns 1997). These data suggest that metabolism of 3,3 -dichlorobenzidine by infants will differ from that in adults in extent, rate, or both. 

Neuwald, A.F. and Landsman, D. (1997) GCN5-related histone N-acetyltransferases belong to a diverse superfamily that includes the yeast SPTIO protein. Trends in Buxdiemical Sciences, 22 (5), 154—155. 

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