Acetyl coenzyme A acetyltransferase

Several pharmacogenomic studies, mainly in animal models, have characterized the molecular mechanisms contributing to the lipidlowering effect of fibrates. Hepatic transcription profiling of clofibrate or gemfibrozil-treated WT rats demonstrated increased expression of many genes involved in beta-oxidation, as well as FFA and cholesterol synthesis, including fatty acyl-Coenzyme A oxidase [45, 191, 192], acetyl-Coenzyme A acetyltransferase... 

Stim-Herndon KP, Petersen DJ, Bennett GN (1995) Molecular characterization of the acetyl coenzyme A acetyltransferase (thiolase) from Clostridium... 

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

The preferred substrates of acetyltransferases are amino-groups of antibiotics, like chloramphenicol, strepto-gramin derivatives, and the various aminoglycosides. The modification is believed to block a functional group involved in the drug-target-interaction. All acetyltransferases use acetyl-coenzyme A as cofactor. 

Acetylcholine synthesis and neurotransmission requires normal functioning of two active transport mechanisms. Choline acetyltransferase (ChAT) is the enzyme responsible for ACh synthesis from the precursor molecules acetyl coenzyme A and choline. ChAT is the neurochemical phenotype used to define cholinergic neurons although ChAT is present in cell bodies, it is concentrated in cholinergic terminals. The ability of ChAT to produce ACh is critically dependent on an adequate level of choline. Cholinergic neurons possess a high-affinity choline uptake mechanism referred to as the choline transporter (ChT in Fig. 5.1). The choline transporter can be blocked by the molecule hemicholinium-3. Blockade of the choline transporter by hemicholinium-3 decreases ACh release,... 

LENZ, R., ZENK, M.H., Acetyl coenzyme A salutaridinol 7-O-acetyltransferase from Papaver somniferum plant cell cultures, J. Biol. Chem., 1995, 270, 31091-31096. 

Selected entries from Methods in Enzymology [vol, page(s)] Assay, 1, 611 3, 935-938 63, 33 separation by HPLC, 72, 45 extraction from tissues, 13, 439 formation of, 1, 486, 518, 585 5, 466 free energy of hydrolysis, 1, 694 substrate for the following enzymes [acetyl-coenzyme A acyl carrier protein transacylase, 14, 50 acetyl-coenzyme A carboxylase, 14, 3, 9 acetyl-coenzyme A synthetase, 13, 375 N-acetyltransferase, 17B, 805 aminoacetone... 

UV/Vis-spectroscopy is the classical method of analysis of enzyme activity. The principle is the change in absorption behavior of a substrate during the reaction process, for example by modification or Hberation of a chromophoric function. A number of enzymes from different classes can be assayed spectrophoto-metrically using their natural substrates or cofactors. In this way, activity of acetyltransferases can be estimated by measurement of absorption of acetyl coenzyme A at 232 nm [33]. Oxidoreductases which require a cofactor, e.g., NAD/NADH, to carry out the transfer of hydrogen can be characterized by measuring the absorption of this cofactor depending on its oxidation stage [33]. 

As their name implies, the A-acetyltransferase (NAT) enzymes catalyze to a drug molecule the conjugation of an acetyl moiety derived from acetyl coenzyme A. Examples of this type of reaction are depicted in Figure 4.1. The net result of this conjugation is an increase in water solubility and increased elimination of the compound. The NATs identified to date and involved in human drug metabolism include NAT-1 and NAT-2. Little overlap in substrate specificities of the two isoforms appears to exist. NAT-2 is a polymorphic enzyme, a... 

Acetylcholine synthesis. Acetylcholine (ACh) is a prominent neurotransmitter, which is formed in cholinergic neurons from two precursors, choline and acetyl coenzyme A (AcCoA) (Fig. 12—8). Choline is derived from dietary and intraneuronal sources, and AcCoA is synthesized from glucose in the mitochondria of the neuron. These two substrates interact with the synthetic enzyme choline acetyltransferase to produce the neurotransmitter ACh. 

The activation event Acetylcholine is synthesized from choline and acetyl coenzyme A (Acetyl-CoA) by the enzyme choline acetyltransferase (ChAT) and is immediately stored in small vesicular compartments closely attached to the cytoplasmic side of the presynaptic membranes. 

A Matsuda, H Sugiura, K Matsuyama, H Matsumoto, S Ichikawa, KI Komatsu. Cloning and disruption of the cefG gene encoding acetyl coenzyme A deacetylcephalosporin C O-acetyltransferase from Acremonium chrysogenum. Biochem Biophys Res Commun 186 40-46, 1992. 

Acetylation reactions catalyzed by acetyltransferase enzymes involve the attachment of the acetyl moiety, shown as the final step in glutathione conjugation and the production of a mercapturic acid conjugate in Figure 7.10. The cofactor upon which the acetyltransferase enzyme acts in acetylation is acetyl coenzyme A ... 

Conversion of (S)-reticuline to its ( )-epimer is the first committed step in morphinan alkaloid biosynthesis in certain species. 1,2-Dehydroreticuline reductase catalyzes the stereospecific reduction of 1,2-dehydroreticuline to (7 )-reticuline.39 Intramolecular carbon-carbon phenol coupling of (if)-reticuline by the P450-dependent enzyme salutaridine synthase (STS) results in the formation of salutaridine.40 The cytosolic enzyme, salutaridine NADPH 7-oxidoreductase (SOR), found in Papaver bracteatum and P. somniferum, reduces salutaridine to (7S)-salutaridinol.41 Conversion of (7S)-salutaridinol into thebaine requires closure of an oxide bridge between C-4 and C-5 by acetyl coenzyme A salutaridinol-7-0-acetyltransferase (SAT). The enzyme was purified from opium poppy cultures and the corresponding gene recently isolated (Fig.7.2).42,43 In the last steps of morphine... 

Xu 2001), glutathione (glutathione S-transferases, Raney et al. 1992 Slone 1995), acetyl-coenzyme A (N-acetyltransferases) or S-adenosylmethionine (methyltransferases). NADPH as a cofactor has to be added if cytosolic reductases are the aim of interest (Inaba 1989). 

W. P. Jencks, M. Gresser, M. S. Valenzuela, and F. C. Huneeus. Acetyl coenzyme a arylamine acetyltransferase. Measurement of the steady state concentration of the acetyl-enzyme intermediate. J. Biol. Chem., 247 3756-3760, 1972. 

APH). Chloramphenicol is attacked by chloramphenicol acetyltransferases (CAT). Acetyltransferases attack susceptible amino groups and require acetyl coenzyme A, while AAD or APH enzymes attack susceptible hydroxyl groups and require ATP (or another nucleotide triphosphate). 

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