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Biotransformation of Xenobiotics in Living Systems—Metabolism of Drugs: Partnership of Liver and Gut Microflora
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Methylation is a relatively minor conjugative pathway in drug metabolism and is engaged more with the metabolism of some endogenous compounds such as melatonin, histamine, serotonin, and dopamine. This reaction is catalyzed by methyltransferases, which transfer a methyl group from the methyl donor S-adenosyl-L-methionine (SAM) to their substrates. Opposite to other phase II reactions, methylation reduces the polarity of substrates. The most common outcome of methylation is deactivation of a compound. Depending of substrates, there are different types of methyltransferases: S-methyltransferases, O-methyltransferases, and N-methyltransferases.
The expression of Phase II drug-metabolizing enzymes in human B-lymphoblastoid TK6 cells
Published in Journal of Environmental Science and Health, Part C, 2022
Xilin Li, Yuxi Li, Kylie G. Ning, Si Chen, Lei Guo, Jessica A. Bonzo, Nan Mei
On the other hand, the important role of Phase II enzymes in metabolism cannot be overlooked. For example, it is well-documented that sulfotransferases (SULT) and N-acetyltransferase (NAT) are required for the bioactivation of heterocyclic amines.10 In our recent study, we surprisingly found that TK6 cells can biotransform luteolin, a flavonoid, to a less toxic metabolite, diosmetin, in a time-dependent manner without addition of any exogenous enzyme systems.11 This O-methylation reaction is likely catalyzed by a Phase II enzyme – catechol O-methyltransferase, suggesting that TK6 cells may not be completely “incompetent” in exogenous drug/chemical metabolism. However, no study has systematically investigated the Phase II enzymatic profile of TK6 cells. Therefore, to fill this knowledge gap, the current short communication surveyed the gene and protein expression profiles of a panel of major Phase II drug-metabolizing enzymes in TK6 cells. Primary human hepatocytes (PHHs), which are considered the in vitro gold-standard for liver drug metabolism enzyme expression and activity,12 and the human hepatoma-derived cell line HepG2, which lacks drug-metabolizing activities,13 were included for comparison to the TK6 cell line. This study characterized the baseline expression of Phase II drug metabolizing enzymes in TK6 cells and can serve as a reference for the Phase II enzyme expression profile of this commonly used cell line.
The association between COMT rs4680 and 5-HTTLPR genotypes and concussion history in South African rugby union players
Published in Journal of Sports Sciences, 2018
Sarah Mc Fie, Shameemah Abrahams, Jon Patricios, Jason Suter, Michael Posthumus, Alison V. September
An individual’s personality is the result of a complex interplay between genetic and environmental factors (Bouchard, 1994). Personality is in part determined by the subtle differences in neural connections, neural architecture, and neurotransmission within certain key areas of the brain, including the prefrontal cortex (Davidson, 2001; Kennis, Rademaker, & Geuze, 2013). Polymorphisms involved in the regulation of neurotransmitter systems are the most frequently investigated candidates in genetic association studies of personality, due to their potential roles in modulating neurotransmission (Balestri, Calati, Serretti, & De Ronchi, 2014). Within those studies, two of the most routinely examined functional polymorphisms are the catechol-O-methyltransferase (COMT) rs4680 single nucleotide polymorphism (SNP) and the serotonin-transporter-linked polymorphic region (5-HTTLPR) (Balestri et al., 2014).
Arsenic, cadmium, and mercury-induced hypertension: mechanisms and epidemiological findings
Published in Journal of Toxicology and Environmental Health, Part B, 2018
Airton da Cunha Martins, Maria Fernanda Hornos Carneiro, Denise Grotto, Joseph A Adeyemi, Fernando Barbosa
Catecholamines are degraded by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT) by donating a methyl group to these catecholamines (Revis 1978). The COMT requires the use of the methyl group provided by coenzyme S-adenosylmethionine (SAM) (Revis 1978). However, exposure to Hg decreases methylation, since this metal may inactivate SAM resulting in consequent inactivation of COMT (Torres, Rai, and Hardiek 2000; Yeter, Deth, and Kuo 2013). Moreover, Hg2+ may affect contractions of smooth or cardiac muscle by compromising the ATP-dependent ability to enable Ca2+ to permeate the sarcoplasmic reticulum promoting elevated in cytoplasmic Ca2+ levels (Yeter, Deth, and Kuo 2013). This event results in enhanced muscle contraction, thereby contributing to hypertension pathophysiology (Torres, Rai, and Hardiek 2000; Yeter, Deth, and Kuo 2013).