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Renal Drug-Metabolizing Enzymes in Experimental Animals and Humans
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
GSH conjugation generally functions as a detoxification pathway. However, compounds may undergo bioactivation following GSH conjugation. Recent studies have described enzymes that metabolize S-cysteine conjugates via transamination and β elimination. This work has demonstrated the role of metabolism in the nephrotoxicity of some S-cysteine conjugates. Both deamination and β elimination are catalyzed by pyridoxal phosphate-dependent enzymes. The balance between β elimination and/or deamination depends on the properties of the enzyme and/or the chemical properties of the substrate. Both reactions are possible with a single substrate and with one enzyme. Deamination of amino acids by transamination involves the transfer of an amino group from a donor amino acid to an acceptor a-keto acid and subsequent decarboxylation. Glutamine transaminase K from rat kidney has been shown to catalyze the transamination of S-cysteine conjugates with a-keto-γ-methiolbutyrate (Stevens et al., 1986). Transamination of cysteine conjugates with other α-keto acids and by other enzymes has also been reported; for example, a flavin-dependant amino acid oxidase from rat kidney catalyzes the oxidative deamination of some S-cysteine conjugates with the concomitant reduction of molecular oxygen to hydrogen peroxide (Hamilton, 1985).
Functions of the Liver
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
The liver has an important role in protein catabolism. The rate of protein turnover in the liver is 10 days, which contrasts sharply with the rate of 180 days for muscle proteins. Amino acid degradation is by transamination, deamination and decarboxylation. Oxidative deamination breaks down surplus amino acids and releases energy. Deamination may be coupled with the transfer of an amino group from one amino acid to another (transamination). These reactions produce acetyl CoA, oxoglutarate, succinyl CoA, oxaloacetate and fumarate, all of which enter the citric acid cycle. Amino acids (such as arginine, histidine, lysine, methionine, threonine, phenylalanine and tryptophan) are degraded mainly in the liver, whereas aspartic acid, glutamic acid, glycine, proline and alanine are metabolized in both hepatic and muscle tissue.
Attributes of Peripheral Dopamine and Dopamine Receptors
Published in Nira Ben-Jonathan, Dopamine, 2020
Without the restricted space of a synapse, DA is released from peripheral nonneuronal cells into the extracellular space and diffuses away from the producing cells into the blood. DA can then reach its target cells via the circulation and can also become inactivated by metabolic enzymes located either at adjacent or at remote sites. Deamination of peripheral DA can be done by two isoenzymes, MAO-A and MAO-B, which are highly expressed in the liver, with a lower expression in the myocardium, lung, kidney, and duodenum [20]. O-methylation is carried out by COMT, also having the highest activity in the liver, followed by the kidney, stomach, and intestine [21].
Diversity in matrilineages among the Jomon individuals of Japan
Published in Annals of Human Biology, 2023
Fuzuki Mizuno, Yasuhiro Taniguchi, Osamu Kondo, Michiko Hayashi, Kunihiko Kurosaki, Shintaroh Ueda
In this study, using combined target enrichment and NGS analysis, we obtained the complete nucleotide sequence information for four mitogenomes of the Initial Jomon individuals, with sufficient depth. Table 1 shows the results obtained, with high accuracy, for the seven individuals, in the study by Mizuno et al. (2020) and this study, with Iyai 10 having a depth of 61, while Iyai 3, Iyai 12, and Iyai 15 having depths of over 200. Sufficient depth and full-length mitogenome sequences were obtained for all the individuals. Their concordance on consensus sequences was 0.989, 0.988, 0.986, and 0.988 for Iyai 3, 10, 12, and 15, respectively. Figure S1 shows the deamination pattern, an indicator of ancient DNA, observed in all the individuals analysed in this study, similar to the results obtained in our previous studies (Mizuno et al. 2020, 2021).
Can we reduce autism-related gastrointestinal and behavior problems by gut microbiota based dietary modulation? A review
Published in Nutritional Neuroscience, 2021
Nalan Hakime Nogay, Marcia Nahikian-Nelms
The catabolism of bacterial amino acids occurs through mechanisms that require deamination or decarboxylation reactions in the human intestine [46]. Protein consumption ensures an increase in all microbial densities. The consumption of animal-derived proteins increases the relative abundance of Bacteroides, Alistipes, Bilophil, and Ruminococcus while decreases that of Bifidobacterium. Plant-derived proteins increase the relative abundance of Bifidobacterium and Lactobacillus and decrease those of Bacteroides and C. perfringens [13]. In a study, the stool samples of 98 individuals were examined to evaluate the effect of diet on the microbiota. Bacteroides was found to have a positive relationship with animal proteins, various amino acids, and saturated fats and a negative relationship with Prevotella, which was associated with high-carbohydrate and simple sugar intake [49].
Functional genetic evaluation of DNA house-cleaning enzymes in the malaria parasite: dUTPase and Ap4AH are essential in Plasmodium berghei but ITPase and NDH are dispensable
Published in Expert Opinion on Therapeutic Targets, 2019
Hirdesh Kumar, Jessica Kehrer, Mirko Singer, Miriam Reinig, Jorge M. Santos, Gunnar R. Mair, Friedrich Frischknecht
The haploid nature of the Plasmodium genome and its rapid DNA replication cycles perhaps pose an increased risk for the mis-incorporation of non-canonical nucleotides into the DNA; yet the enzymes preventing such DNA damage in the malaria parasite are largely unknown. Intracellular nucleotide pools are essential DNA building blocks, serve as energy storage molecules, and act as cofactors and regulators in various metabolic and signal transduction pathways. Reactive oxygen species produced during cellular redox reactions can oxidize the DNA precursor pool and produce so-called non-canonical deoxynucleoside triphosphates (dNTPs). For example oxidative deamination of the nitrogenous base produces deoxyinosine triphosphate (dITP) from deoxyadenosine triphosphate (dATP), deoxyuridine triphosphate (dUTP) from deoxycytosine triphosphate (dCTP) and deoxyxanthosine triphosphate (dXTP) from deoxyguanosine triphosphate (dGTP). Thymine lacks a free amino group and therefore is not oxidatively deaminated. Oxidation of purine bases on the other hand results in nucleotides like 2-oxo-dATP, 8-oxo-dATP, and 8-oxo-dGTP. Such modified nucleotide analogs can be incorporated into DNA during replication [10,11]. When recognized by the DNA repair system, single strand breaks are introduced which need repairing. As a consequence, cellular growth can slow down or the cell may die due to the accumulation of deleterious mutations and double strand breaks [11].