N-acetyl transferases

Sanfilippo C MPS IIIC Acetyl CoA glucosamine N-acetyl transferase Heparan sulfate... 

SSRI = Selective serotonin reuptake inhibitor NSAID = Nonsteroidal anti-inflammatory drug CYP = cytochrome P-450 NAT2 = N-acetyl transferase type 2 J = Japanese C = Chinese A = African American. Poor metabolizers are not always at increased risk of ADR. 

These strategies are aimed at either cytosolic enzymes, such as L-amino acid decarboxylase, 3-lyase and N-acetyl transferase, or enzymes that are expressed at the brush border of the proximal tubule and to a lesser extent on the basolateral membrane, such as y-glutamyl transpeptidase (GGT). 

In rabbits, the activity of liver N-acetyl transferase was studied in vitro and found to show trimodal or bimodal distributions. 

Evans DAP. N-Acetyl transferase. In Kalow W, ed. Pharmacogenetics of Drug Metabolism. New York Pergamon, 1993 95. 

Little is known of the N-acetyl transferase(s) responsible for the acetylation of the S-substituted cysteine. It is found in the microsomes of the kidney and the liver, however, and is specific for acetyl CoA as the actyl donor. It is distinguished from other N-acetyltransferases by its substrate specificity and subcellular location. 

Neomycin 3 -phosphotransferase Hygromycin phosphotransferase Puromycin N-acetyl-transferase... 

Acetylator status Refers to ability to acetylate organic compounds in the liver. A rapid acetylator refers to an individual whose N-acetyl transferase is hyperactive. Such individuals are more likely to require larger doses of drugs such as phenelzine. Conversely, slow acetylators have a genetically linked deficit in N-acetyl transferase and therefore require a lower dose of the drug. 

McQuilkin SH, Nierenberg DW, Bresnick E. Analysis of within-subject variation of caffeine metabolism when used to determine cytochrome P4501A2 and N-acetyl-transferase-2 activities. Cancer Epidemiol Biomarkers Prev 1995 4 139-146. 

Cytosol easy to use, cheap addition of cofactors (simple mixtures), Only not membrane-bound metabolizing enzymes such as alcohol dehydrogenases, sulfotransferases, glutathione S transferase, N-acetyl transferases partial metabolic profile, induction not modeled... 

Since liver is the most important organ for metabolism investigations the procedures described here focus on liver cytosol exemplarily. Liver cytosol fraction contains soluble Phase I and Phase II enzymes which play an important role in drug metabolism (Brandon 2003). These are alcohol and aldehyde dehydrogenases, epoxide hydrolases, sulfotransferases, glutathione S transferase, N-acetyl transferases, and methyl transferases. Therefore, in cytosolic preparations these biotransformation steps can be studied. Cytosolic fractions are commercially available (BDGentest, Invitro Technologies, Xenotech and others) or easy to prepare, alternatively. 

Tuberculous patients lacking in liver N-acetyl transferase who are treated with isoniazid are likely to develop polyneuritis (39). An enzyme abnormality is also responsible for the precipitation of acute intermittent porphyria by the barbiturate drugs (40). Likewise, the rare hereditary resistance to coumarin anticoagulant drugs is thought to be due to an enzyme deficiency (41). 

JDP Glucuronosyl Transferase Glutathione S-Transferase N-Acetyl Transferase Su Ifotra nsf erase Me th y It ransfe rase... 

The N-acetyl transferase (NAT) polymorphism is one of the earliest pharmacogenetic targets recognized and characterized. NATs are Phase II enzymes that catalyze the transfer. of an acetyl moiety from acetyl-CoA to homocychc and heterocyclic arylamines and hydrazines. Substrates include drugs, carcinogens, toxicants, and possibly endogenous compounds. Slow metabolizer phenotypes, which may affect up to 90% of some populations, are manifested by changes in protein expression, protein stability, and enzyme kinetics. 

Grant DM, Goodfellow GH, Sugamori KS, Durette K. Pharmacogenetics of the human arylamine N-acetyl-transferases. Pharmacol 2000 61 204-11. 

Bhaldia S, et al Arylamine N-acetyl transferases a pharmacogenomic approach to drug metabolism and... 

Vatsis KP, Weber WW, Bell DA, Dupret JM, Evans DAP, Grant DM, et al. Nomenclature for N-acetyl-transferases. Pharmacogenetics 1995 5 1-17. 

Windmill KF, Gaedigk A, Hall PM, Samaratunga H, Grant DM, McManus ME. Localization of N-acetyl-transferases NATl and NAT2 in human tissues. Toxicol Sci 2000 54 19-29. 

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