Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of aldehyde dehydrogenase-free mitochondrial preparations with biogenic amines serotonin, tyramine, 2-phenylethylamine and 5-methoxytryptamine resulted in inhibition of enzymes activity of both outer (rotenone-insensitive NADH-cytochrome c reductase) and inner (succinate dehydrogenase, succinate cytochrome c reductase) mitochondrial membranes. Solubilization of mitochondria after the incubation did not influence the amine-induced alteration of succinate dehydrogenase activity. Pretreatment of the organelles with a mixture containing chlorgyline and deprenyl completely inhibited monoamine oxidase (MAO) activity and prevented the effects of all the amines studied on mitochondrial enzymes. MAO-dependent effects of 5-methoxytryptamine were fully reproduced by 5-methoxyindolyl-3-acetaldehyde (one of probable products of 5-methoxytryptamine deamination). The effect of the aldehyde was not prevented by chlorgyline and deprenyl. After selective inhibition of MAO-A by chlorgyline the order of MAO-B-dependent effects of biogenic amines on mitochondrial enzymes studied was as follows: tyramine greater than or equal to 2-phenylethylamine much greater than serotonin. In deprenyl pretreated mitochondria the potency of MAO-A-dependent effects of these amines was: serotonin greater than tyramine much greater than much greater than 2-phenylethylamine. The data obtained suggest that the product(s) of oxidative deamination of biogenic amines (probably the aldehydes) catalyzed by both types of MAO (MAO-A and MAO-B) are able to regulate the energy functions of mitochondria.
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PMID:[The role of monoamine oxidase in the regulation of mitochondrial energy functions]. 175 90

This review summarizes advances in our understanding of the biochemical events which underlie the remarkable neurotoxic action of MPTP (1-methyl-4-phenyl-1-1,2,3,6-tetrahydropyridine) and the parkinsonian symptoms it causes in primates. The initial biochemical event is a two-step oxidation by monoamine oxidase B in glial cells to MPP+ (1-methyl-4-phenylpyridinium). A large number of MPTP analogs substituted in the aromatic (but not in the pyridine) ring are also oxidized by monoamine oxidase A or B, is in some cases faster than any previously recognized substrate. Alkyl substitution at the 2'-position changes MPTP, a predominantly B type substrate, to an A substrate. Following concentration in the dopamine neurons by the synaptic system, which has a high affinity for the carrier, MPP+ and its positively charged neurotoxic analogs are further concentrated by the electrical gradient of the inner membrane and then more slowly penetrate the hydrophobic reaction site on NADH dehydrogenase. Both of the latter events are accelerated by the tetraphenylboron anion, which forms ion pairs with MPP+ and its analogs. Mitochondrial damage is now widely accepted as the primary cause of the MPTP induced death of the nigrostriatal cells. The molecular target of MPP+, its neurotoxic product, is NADH dehydrogenase. Recent experiments suggest that the binding site is at or near the combining site of the classical respiratory inhibitors, rotenone and piericidin A.
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PMID:Mechanism of the neurotoxicity of MPTP. An update. 225 61

MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a selective nigrostriatal neurotoxin, is bioactivated by MAO-B (and less effectively by MAO-A) to 2,3-MPDP+ and this intermediate undergoes further oxidation to MPP+, partly through the activity of MAO forms. MPTP and its two primary metabolites are competitive inhibitors of both A and B forms of MAO. MPTP and 2,3-MPDP+ are also mechanism-based inactivators of both forms of the enzyme. A catalytic mechanism, involving the formation of radical intermediates, is proposed for the MAO-mediated oxidation of MPTP. Post-oxidation biochemical sequelae, possibly involved in the expression of neurotoxicity, include the active accumulation of MPP+ via dopamine reuptake systems, the energy-driven uptake of MPP+ by mitochondria and the inhibition of NADH dehydrogenase by pyridine derivatives. A scheme linking these events as steps in the molecular mechanism of action of MPTP is proposed and discussed in terms of the selective toxicity of the neurotoxin towards nigrostriatal cells.
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PMID:Processing of MPTP by monoamine oxidases: implications for molecular toxicology. 329 17

To date, no specific drug has been discovered for the treatment of COVID-19 and hence, people are in a state of anxiety. Thus, there is an urgent need to search for various possible strategies including nutritional supplementation. In this study, we have tried to provide a reference for protein supplementation. Specifically, 20 marine fish proteins were subjected to in silico hydrolysis by gastrointestinal enzymes, and a large number of active peptides were generated. Then, the binding abilities of these peptides to SARS-CoV-2 main protease and monoamine oxidase A were assessed. The results showed that NADH dehydrogenase could be a good protein source in generating potent binders to the two enzymes, followed by cytochrome b. In addition, some high-affinity oligopeptides (VIQY, ICIY, PISQF, VISAW, AIPAW, and PVSQF) were identified as dual binders to the two enzymes. In summary, the supplementation of some fish proteins can be helpful for COVID-19 patients; the identified oligopeptides can be used as the lead compounds to design potential inhibitors against COVID-19 and anxiety.
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PMID:In silico evaluation of marine fish proteins as nutritional supplements for COVID-19 patients. 3252 31