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Paediatric clinical pharmacology
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
N-acetyltransferase type 2 (NAT2). NAT2 activity displays genetic polymorphism mediated by as an autosomal recessive trait [31]. Its distribution is extremely variable from one ethnic group to another. In Caucasian populations, 50 to 70% of individuals are slow acetylators, whereas the percentage is only 5% in Eskimo populations, and more than 90% in Egyptians [32].
Regulation of the Arachidonic Acid Cascade and PAF Metabolism in Reproductive Tissues
Published in Murray D. Mitchell, Eicosanoids in Reproduction, 2020
John M. Johnston, Noriei Maki, Marlane J. Angle, Dennis R. Hoffman
The specific activities of lysoPAF:acetyl-CoA acetyltransferase (Figure 7, reaction V) and PAF acetylhydrolase (reaction VI) in amnion tissue97 were associated with microsomal and cytosolic fractions, respectively, and the pH optimum of these two enzymes in amnion tissue was approximately 7.5. Maximal activity of acetyltransferase was obtained at low concentrations of Ca2+ (on the order of 10−6M). No effect of Ca2+ on acetylhydrolase activity was demonstrated. The specific activities of acetyltransferase and acetylhydrolase in fetal membranes obtained at term after the onset of labor were not significantly different from those obtained from tissue at term before labor or in early gestation. Therefore, the mechanisms involved in the regulation of PAF acetyltransferase by Ca2+ are not clearly defined. Whether Ca2+ activates the enzyme directly or indirectly via Ca2+-dependent protein kinase C, as recently suggested,99,100 is not known. Sanchez-Crespo and colleagues101 have suggested that acetyltransferase is activated by cAMP-dependent phosphorylation.
Xenobiotic Biotransformation
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Xenobiotics or endogenous compounds containing amino, hydroxyl, or sulfhydryl groups are substrates for acetyltransferases [reviewed by King and Glowinski (1983) and Weber and Hein (1985)]. Amines, including aromatic and aliphatic primary amines, hydrazines, hydrazides, and sulfonamides, have been the most widely studied substrates. Endogenous substrates are 5-hydroxy-tryptamine and histamine. The enzymes are cytosolic and are present in several tissues; liver has the highest activity. Acetyl coenzyme A is the co-factor. The enzymes have been designated acetyl CoA: amine acetyl transferases. Sulfamethazine N-acetyltransferase is another term for the enzyme activity; sulfamethazine is the prototype substrate. The activity is characterized by polymorphism across many species, and individuals (or species and strains) are characterized as “slow” or “fast” acetylators. This polymorphism is determined by a single gene locus containing two co-dominant alleles: R = rapid, and r = slow. This polymorphism is an important determinant of susceptibility to toxicity and carcinogenicity of drugs (e.g., isoniazid) or xenobiotics, particularly aromatic amines, which are bioactivated or detoxified by acetylation.
Stereotaxic-assisted gene therapy in Alzheimer’s and Parkinson’s diseases: therapeutic potentials and clinical frontiers
Published in Expert Review of Neurotherapeutics, 2022
Samar O. El Ganainy, Tony Cijsouw, Mennatallah A. Ali, Susanne Schoch, Amira Sayed Hanafy
Similarly, downregulation or deletion of pathogenic proteins contributing to AD development rescued memory deficits and synaptic plasticity in several studies [149–151]. Haploinsufficiency of transmembrane protein-59, a type-I glycoprotein inducing amyloid precursor protein retention, reversed memory impairment and synaptic plasticity in transgenic mice [149]. Moreover, Masmudi-Martín et al. [150] reported that the omission of RGS domain form RGS14 gene reversed object recognition deficits, probably by alleviating the gene suppressive effect on intracellular signaling. A previous study also showed that the downregulation of a key acetyltransferase inhibitor attenuated tau hyperphosphorylation and restored synaptic morphology [151]. In addition, miRNA focally injected in rat hippocampus reprogramed hyperactivated astrocytes that restrict neural regeneration. This technique succeeded to transform those reactive cells into neurons, enhancing neuronal repair and improving memory performance [152].
Protein lysine acetylation and its role in different human pathologies: a proteomic approach
Published in Expert Review of Proteomics, 2021
Orlando Morales-Tarré, Ramiro Alonso-Bastida, Bolivar Arcos-Encarnación, Leonor Pérez-Martínez, Sergio Encarnación-Guevara
The lysine acetyltransferases and histone acetylation were discovered in 1964 by Allfrey and colleagues [23]. They were originally described for their ability to acetylate histone-proteins, which is why they were initially being called HATs. However, they have now been renamed lysine acetyltransferases (KATs). This class of enzymes acetylate conserved lysine residues in target proteins by transferring an acetyl group from AcCoA to the epsilon amino group of the side chains of lysine residues [23]. Despite recent advances in research related to acetylation, the precise quantity of acetyltransferases present in the human cell remains unknown. Three groups of proteins constitute the KAT family: the first group is the GNAT family (GCN5-related N-acetyltransferase). The MYST family (monocytic leukemia zinc finger protein (MOZ), Tip60, Sas2, Sas3/Ybf2) makes up the second group, and p300/CREB-binding protein (CBP) family constitute the last group [24]. KATs have domains additional to the catalytic domain, which interact with other proteins and substrates, including bromodomains and other modification recognition domains [25]. Histones are not the unique targets recognized for KAT enzymes; several transcription factors, coregulators of transcription, in addition to enzymes implied in central metabolic pathways, can be modified by them [26]. Table 1 describes the different KAT families and some of their properties compiled in uniprot database.
Current trends in protein acetylation analysis
Published in Expert Review of Proteomics, 2019
Issa Diallo, Michel Seve, Valérie Cunin, Frédéric Minassian, Jean-François Poisson, Sylvie Michelland, Sandrine Bourgoin-Voillard
Because post-translational modifications (PTMs) are involved in many biological processes and can regulate the protein function by changing stability, localization and activity of proteins, their analysis is critical to understand regulation of biological processes [1]. Among those PTMs, acetylation, discovered in 1963 by Phillips et al. [2], has emerged as one of the major protein PTMs in the cell after phosphorylation [3]. Acetylation is catalyzed by a wide range of acetyltransferases (such as Enzyme Class EC 2.3.1) that transfer acetyl groups (–CO–CH3) from an acetylated molecule like acetyl-coenzyme A onto specific amino acids, which results in addition of an acetyl group on modified species to account for an additional 42 Da [4]. Three major types of acetylation have been described based on the acetylation site in the protein (Figure 1), including: (a) N-terminal acetylation commonly named N-ter acetylation or Nα-acetylation; (b) lysine acetylation commonly named K-acetylation (KAc) or Nε-acetylation; (c) O-acetylation.