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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
Monoamine oxidases (MAOs) are found in the in the outer membrane of mitochondria in most cell types in the body and catalyze deamination and dehydrogenation of primary, secondary, and tertiary amines. They catalyze the breakdown of monoamine neurotransmitters including dopamine, serotonin, and epinephrine and can oxidize xenobiotics such as aniline. The final product of MAOs, CYPs and FMOs are identical in chemical structures, thus the oxidative deamination by MAO can only be distinguished from CYP oxidative deamination by drug and enzyme characterization, not by metabolite structure (Markey, 2007). Two types, MAO-A and MAO-B are identified, which are differentially expressed in different tissues such as liver, brain, lung, kidney, intestine, and blood platelets. Inhibition of MAOs found its application in neurology for the treatment of Parkinson’s disease and in psychiatry for the treatment of depressive disorders (Penner et al., 2012).
The Neurodegenerative Characteristics of Alzheimer’s Disease and Related Multi-Target Drug Design Studies
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Hayrettin Ozan Gülcan, Ilkay Erdogan Orhan
Monoamine oxidase (MAO) enzyme activity is one of the critical steps in the control of the function of several neurotransmitters (e.g., serotonin, dopamine, and norepinephrine). In other words, through the formation of aldehyde derivatives of neurotransmitters via MAO catalyzed oxidative deamination reactions, the amine neurotransmitters are deactivated (Shih et al., 1999). There are two types of MAO enzymes in human, as referred to as MAO-A and MAO-B. They display different tissue distribution and ratios depending on age. Although they are capable of employing a diverse amine substrates, there is some selectivity difference. MAO-A shows selectivity for serotonin, melatonin, norepinephrine, and epinephrine, while MAO-B possesses substrate selectivity for benzylamine and phenethylamine. On the other hand, both enzymes display similar characteristics to catalyze dopamine, tyramine, and tryptamine oxidative deamination reactions (Kalgutkar et al., 2001). Depending on the substrate specificity difference, MAO-A inhibition is mainly preferred as an option in the treatment of some form depression (e.g., to increase the available levels of serotonin, norepinephrine, and dopamine) (Meyer et al., 2006). Parkinson disease–related symptoms are generally related to deficiency of dopamine. Regarding the side effects of MAO-A inhibitors, MAO-B inhibitors (e.g., rasagiline, selegiline) are preferred to increase the available amount of dopamine in CNS (Youdim, 2006).
Biomolecules and Tissue Properties
Published in Joseph W. Freeman, Debabrata Banerjee, Building Tissues, 2018
Joseph W. Freeman, Debabrata Banerjee
Elastin is formed when multiple tropoelastin molecules are covalently bonded together via crosslinks. Tropoelastin is the elastin precursor and is soluble. Tropoelastin is transported to the intercellular space by elastin-binding protein (EBP) and joins with microfibril proteins. Lysine residues in tropoelastin undergo oxidative deamination because of lysyl oxidase, forming desmosine- and isodesmosine-based crosslinks form. The crosslinking creates elastin but also decreases solubility, which is why elastic fibers are a highly insoluble in water. Elastin’s hydrophobicity allows the molecules to slide over one another. This creates stretch and allows recoil in the tissue. The desmosine and isodesmosine crosslinks (covalent bonds) link four elastin molecules. Desmosine and isodesmosine are unique to elastin.
The combined effects of wood vinegar and perfluorooctanoic acid on enzymatic activities, DNA damage and gene transcription in Dugesia japonica
Published in Chemistry and Ecology, 2022
Jianyong Zhang, Na Sun, Jingyi Sun, Bin Wang, Xiaoran Chen, Jing Liu, Bosheng Zhao, Zuoqing Yuan
COX, MAO and SDH are localised to the mitochondrial membrane. PFOA induces dysregulation resulting in oxidative stress [19]. COX binds to the mitochondrial membrane and participates in electron transfer [36]. PFOA and WV increase the activities of COX. These changes in enzymatic activities may be due to mitochondrial dysfunction caused by PFOA [37]. WV probably increased the activities of COX because it is rich in organic acids and participates in the pumping out of protons. MAO is a key enzyme in the outer mitochondrial membrane and plays a role in amine metabolism [38]. In this study, MAO activities were significantly activated and then inhibited by PFOA, implying that MAO activities increased due to PFOA stress and then decreased as a result of tolerance to PFOA. MAO is sensitive to free radicals and responsible for the oxidative deamination of monoamine neurotransmitters including dopamine. The change of MAO activity should be due to oxidative stress induced by PFOA. Because WV is an acid liquid, it can increase MAO enzyme activity. The activity of SDH is closely related to the function of mitochondria. In this study, increase in SDH activity indicated that mitochondrial function was increased under PFOA tress. By contrast, WV decreased SDH activity. This may have been due to antioxidant activities of WV. In general, the above experimental results show that WV functions in biochemical protection of planarians.
Kinetic modeling and statistical optimization of submerged production of anti-Parkinson’s prodrug L-DOPA by Pseudomonas fluorescens
Published in Preparative Biochemistry & Biotechnology, 2022
Ananya Naha, Santosh Kumar Jha, Hare Ram Singh, Muthu Kumar Sampath
Levodopa is an amino acid and a precursor of dopamine. It can easily cross the blood-brain barrier and convert to dopamine by Dopa Carboxylase by a single enzymatic step, thus increasing the store of dopamine in the brain. Unlike dopamine, L-DOPA can be taken orally or intravenously. It is rapidly taken up by dopaminergic neurons and converted to dopamine.[4] The conversion of L-DOPA to dopamine mainly occurs in the periphery as well as in Central Nervous System (CNS) thus facilitating the reuptake of dopamine by the dopamine transporter (DAT) and vesicular monoamine transporter (VMAT). DAT helps to transport dopamine from extracellular to intracellular space, and VMAT reloads dopamine into the vesi hcles. The whole process is energy-dependent and uses Na-K ions for ATP hydrolysis to create a concentration gradient of ions across the presynaptic membrane. This drive opens the transporter and cotransport Na and Cl ions and dopamine from the synaptic cleft. The released K ions in the synaptic cleft help in the equilibration of the ionic gradient across the presynaptic membrane. Metabolism of dopamine by monoamine oxidase (MAO) and catechol-O-methyl transferase (COMT) is one of the effective mechanisms for dopamine inactivation. This includes several pathways like oxidative deamination by MAO, conjugation by glucuronidase or sulfotransferases, and O-methylation by COMT. MAO acts intracellularly and is located at the external membrane of mitochondria, whereas COMT acts extracellularly and is located within the external cell membrane.[5]
Comparative analysis of remediation efficiency and ultrastructural translocalization of polycyclic aromatic hydrocarbons in Medicago sativa, Helianthus annuus, and Tagetes erecta
Published in International Journal of Phytoremediation, 2023
GDH catalyzes reversible reactions such as oxidative deamination of L-glutamate and reductive amination of 2-oxoglutarate, through which it connects the metabolism of nitrogen with the TCA cycle that lies at the center of cell energetics. This enzyme catalyzes deamination, an essential step in the catabolism of amino acids that are accelerated under carbon deficiency in cells. GDH activity stimulation is observed in plants exposed to PAHs while more significant in control. Contradictory, GDH activity decreases when the concentration of PAHs rises (Figure 5c). A high concentration of Phe, Ant, Flu, and Pyr stimulates GDH activity in M. sativa, H. annuus, and T. erecta, maximum GDH was observed in M. sativa (183.78 ± 0.112 Unit mg−1 protein at 700 mg kg−1) in phenanthrene treated soil. On the other hand, Pyrene inhibits GDH activity in all evaluated plants at the highest concentration (700 mg kg−1). Still, simultaneous inhibition of the enzyme was observed in T. erecta, respectively, by 79.519 ± 0.013 Unit mg−1 protein in Pyr. Our results were supported by Shen et al. (2019) PAH exposure significantly increases the nitrate reductase activity, in plants through which the reduction of nitrate to ammonia occurs. This increase in ammonia content and GDH upregulation may explain the increased levels of GDH observed under PAH stress. Zhan et al. (2015) and Xia et al. (2021) researchers also attended similar data in Triticum aestivum, Salix Viminalis, Medicago Sativa, Zea mays, Phaseolus vulgaris, and Ligustrum sempervirens under octane and benzene stress.