Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.3.5.1 (succinate dehydrogenase)
 8,177 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

The effect of age upon monoamine oxidase -A and -B (MAO-A and -B) in 23 different, regions of human brain was determined. There was a significant positive correlation with age in 19 out of 23 regions for MAO-B, but no positive correlation with age was found for MAO-A. The increased MAO-B activity was found, in 5 out of 5 regions tested, to be due entirely to an increased enzyme concentration, rather than due to an increased molecular turnover number of the enzyme. The responses of the mitochondrial marker enzymes succinate dehydrogenase (SDH) and malate dehydrogenase (MDH) were studied in 5 brain regions, and no consistent change in activity found with age. The lysosomal enzyme acid phosphatase was found to tend towards an increased activity with age. No difference in either the specific activities or molecular characteristics of MAO were found between men and women. Cross-correlation studies of the data, after compensation for the effects of age, indicated that the activities of the two enzyme forms are under some form of organized control across the whole brain. Such a finding is consistent with a genetic regulation of the enzyme forms.
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PMID:The effect of age on the activity and molecular properties of human brain monoamine oxidase. 744 Dec 34

Defects in the mitochondrial genome have been associated with Parkinson's and Alzheimer's disease, and apoptosis can be triggered by the presence of energetically compromised mitochondria. Thus, in this study we have examined whether the divalent cations Cu2+ and Mn2+ could influence mitochondrial function in vitro. Mitochondrial electron transport was dose and time dependently reduced by Cu2+ to a greater extent with succinate as a substrate. Following a 60 min preincubation period, Mn2+ dose dependently inhibited electron transport to a greater extent with lactate and malate. In contrast, paradoxical effects were seen following a 5 min preincubation period with Mn2+. Cu2+ dose-dependently reduced NADH-dependent lactate dehydrogenase (LDH) activity, with almost complete inhibition apparent at 10 microM. An initial induction of LDH by 10 microM Mn2+ was partially reversed by higher concentrations of the metal. Cu2+ dose-dependently reduced flavin adenine dinucleotide (FAD)-dependent monoamine oxidase A (MAO-A) activity in a time-independent manner, with an IC50 value approximately 20 microM, whereas Mn2+ had no effect. In conclusion, it is proposed that Cu2+ and Mn2+ have differential effects on nicotinamide adenine dinucleotide (NAD) and FAD-dependent mitochondrial enzymes at the level of the essential cofactors. Cu2+ appears to exert an inhibitory effect on both NAD and FAD-dependent enzymes, but predominantly against the latter, including MAO-A and succinate dehydrogenase. The complex responses to Mn2+ may be due to dose-related effects on the interconversion of NAD and NADH and reversible enzymatic reactions employing this nucleotide cofactor.
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PMID:Paradoxical effects of copper and manganese on brain mitochondrial function. 1126 70

Intrastriatal administration of the succinate dehydrogenase (SDH) inhibitor malonate produces neuronal injury by a "secondary excitotoxic" mechanism involving the generation of reactive oxygen species (ROS). Recent evidence indicates dopamine may contribute to malonate-induced striatal neurodegeneration; infusion of malonate causes a pronounced increase in extracellular dopamine and dopamine deafferentation attenuates malonate toxicity. Inhibition of the catabolic enzyme monoamine oxidase (MAO) also attenuates striatal lesions induced by malonate. In addition to forming 3,4-dihydroxyphenylacetic acid, metabolism of dopamine by MAO generates H2O2, suggesting that dopamine metabolism may be a source of ROS in malonate toxicity. There are two isoforms of MAO, MAO-A and MAO-B. In this study, we have investigated the role of each isozyme in malonate-induced striatal injury using both pharmacological and genetic approaches. In rats treated with either of the specific MAO-A or -B inhibitors, clorgyline or deprenyl, respectively, malonate lesion volumes were reduced by 30% compared to controls. In knock-out mice lacking the MAO-A isoform, malonate-induced lesions were reduced by 50% and protein carbonyls, an index ROS formation, were reduced by 11%, compared to wild-type animals. In contrast, mice deficient in MAO-B showed highly variable susceptibility to malonate toxicity precluding us from determining the precise role of MAO-B in this form of brain damage. These findings indicate that normal levels of MAO-A participate in expression of malonate toxicity by a mechanism involving oxidative stress.
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PMID:Striatal damage and oxidative stress induced by the mitochondrial toxin malonate are reduced in clorgyline-treated rats and MAO-A deficient mice. 1509 36

The trends of novel AD therapeutics are focused on multitarget-directed ligands (MTDLs), which combine cholinesterase inhibition with additional biological properties such as antioxidant properties to positively affect neuronal energy metabolism as well as mitochondrial function. We examined the in vitro effects of 10 novel MTDLs on the activities of mitochondrial enzymes (electron transport chain complexes and citrate synthase), mitochondrial respiration, and monoamine oxidase isoform (MAO-A and MAO-B) activity. The drug-induced effects of 7-MEOTA-adamantylamine heterodimers (K1011, K1013, K1018, K1020, and K1022) and tacrine/7-MEOTA/6-chlorotacrine-trolox heterodimers (K1046, K1053, K1056, K1060, and K1065) were measured in pig brain mitochondria. Most of the substances inhibited complex I- and complex II-linked respiration at high concentrations; K1046, K1053, K1056, and K1060 resulted in the least inhibition of mitochondrial respiration. Citrate synthase activity was not significantly inhibited by the tested substances; the least inhibition of complex I was observed for compounds K1060 and K1053, while both complex II/III and complex IV activity were markedly inhibited by K1011 and K1018. MAO-A was fully inhibited by K1018 and K1065, and MAO-B was fully inhibited by K1053 and K1065; the other tested drugs were partial inhibitors of both MAO-A and MAO-B. The tacrine/7-MEOTA/6-chlorotacrine-trolox heterodimers K1046, K1053, and K1060 seem to be the most suitable molecules for subsequent in vivo studies. These compounds had balanced inhibitory effects on mitochondrial respiration, with low complex I and complex II/III inhibition and full or partial inhibition of MAO-B activity.
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PMID:Effects of Novel Tacrine Derivatives on Mitochondrial Energy Metabolism and Monoamine Oxidase Activity-In Vitro Study. 3308 24