Flavoenzyme catalysed oxidation of amines: roles for flavin and protein-based radicals

Rigby, Stephen E. J.; Basran, Jaswir; Combe, Jonathan P.; Mohsen, Al‐Walid; Toogood, Helen S.; Thiel, Adam van; Sutcliffe, Michael J.; Leys, D.; Munro, Andrew W.; Scrutton, Nigel S.

doi:10.1042/bst0330754

Cited by 16 publications

(16 citation statements)

References 44 publications

(64 reference statements)

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“…A major finding in this study is that the increase in O 2 ⅐ Ϫ induced by serotonin was attenuated by inhibition of the flavin-containing enzyme MAO (46). Serotonin is metabolized avidly by MAO, which is localized in the outer mitochondrial membrane (4,42,55).…”

Section: The Data Indicate That Serotonin Increases Omentioning

confidence: 91%

Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves

Pena‐Silva

Miller

Chu

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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Heart valve disease and pulmonary hypertension, in patients with carcinoid tumors and people who used the fenfluramine-phentermine combination for weight control, have been associated with high levels of serotonin in blood. The mechanism by which serotonin induces valvular changes is not well understood. We recently reported that increased oxidative stress is associated with valvular changes in aortic valve stenosis in humans and mice. In this study, we tested the hypothesis that serotonin induces oxidative stress in human heart valves, and examined mechanisms by which serotonin may increase reactive oxygen species. Superoxide (O2*.-) was measured in heart valves from explanted human hearts that were not used for transplantation. (O2*.-) levels (lucigenin-enhanced chemoluminescence) were increased in homogenates of cardiac valves and blood vessels after incubation with serotonin. A nonspecific inhibitor of flavin-oxidases (diphenyliodonium), or inhibitors of monoamine oxidase [MAO (tranylcypromine and clorgyline)], prevented the serotonin-induced increase in (O2*.-). Dopamine, another MAO substrate that is increased in patients with carcinoid syndrome, also increased (O2*.-) levels in heart valves, and this effect was attenuated by clorgyline. Apocynin [an inhibitor of NAD(P)H oxidase] did not prevent increases in (O2*.-) during serotonin treatment. Addition of serotonin to recombinant human MAO-A generated (O2*.-), and this effect was prevented by an MAO inhibitor. In conclusion, we have identified a novel mechanism whereby MAO-A can contribute to increased oxidative stress in human heart valves and pulmonary artery exposed to serotonin and dopamine.

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Section: The Data Indicate That Serotonin Increases Omentioning

confidence: 91%

Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves

Pena‐Silva

Miller

Chu

et al. 2009

American Journal of Physiology-Heart and Circulatory Physiology

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“…Nature is often redundant with regard to the generation of different protein families that catalyze identical chemical reaction and flavin-dependent enzymes are known to bring about net amine and alcohol oxidations that are very similar to the reactions catalyzed by the quinocofactor-dependent enzymes discussed herein. 143,144 The quinone-dependent enzymes are, in fact, more restrictive than flavin-dependent systems, either acting exclusively on primary amine substrates (TTQ, CTQ, TPQ, and LTQ) or a select number of primary alcohols (in the case of PQQ). One very intriguing feature of this class of redox cofactors is their predominant function outside of the cell: either within the periplasmic space of Gram-negative bacteria (for the PQQ-, TTQ- and CTQ-dependent enzymes) 145-147 or within the extracellular matrix of mammals (the LTQ-dependent reaction of lysyl oxidases).…”

Section: Overviewmentioning

confidence: 99%

Intrigues and Intricacies of the Biosynthetic Pathways for the Enzymatic Quinocofactors: PQQ, TTQ, CTQ, TPQ, and LTQ

2013

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CONTENTS 1. Introduction 4343 2. PQQ (Pyrroloquinoline Quinone) 4343 2.1. General Background 4343 2.2. Biosynthetic Process 4345 3. TTQ (Tryptophan Tryptophylquinone) 4347 3.1. General Background 4347 3.2. Biosynthetic Process 4348 3.3. Mechanism of MauG 4349 4. CTQ (Cysteine Tryptophyl Quinone) 4350 4.1. General Background 4350 4.2. Biosynthetic Process 4351 4.3. Relationship to Biosynthesis of TTQ 4352 5. TPQ (Trihydroxyphenylalanine Quinone) 4353 5.1. General Background 4353 5.2. Biosynthetic Process 4354 5.3. Relationship of the Pathway for TPQ Biosynthesis to That for PQQ, TTQ, and CTQ 4360 6. LTQ (Lysyl Tyrosine Quinone) 4360 6.1. General Background 4360 6.2. Biosynthetic Process 4360 7. Overview 4361 Author Information 4362 Corresponding Author 4362 Notes 4363 Biographies 4363 Acknowledgments 4363 References 4363 Note Added in Proof 4365

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“…Semiquinones are important in a variety of biological systems [38, 39]. Knowledge of semiquinone relaxation rates is needed for relaxation enhancement measurements of interspin distances such as between the iron-sulfur cluster and the flavin adenine dinucleotide (FAD) semiquinone of electron transfer flavoprotein ubiquinone oxidoreductase (ETF-QO) [40, 41].…”

Section: Introductionmentioning

confidence: 99%

Electron spin relaxation rates for semiquinones between 25 and 295K in glass-forming solvents

Kathirvelu

Sato

Eaton

2009

Journal of Magnetic Resonance

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Electron spin lattice relaxation rates for five semiquinones (2,5-di-t-butyl-1,4-benzosemiquinone, 2,5-di-t-amyl-1,4-benzosemiquinone, 2,5-di-phenyl-1,4-benzosemiquinone, 2,6-di-t-butyl-1,4-benzosemiquinone, tetrahydroxy-1,4-benzosemiquione) were studied by long-pulse saturation recovery EPR in 1:4 glycerol:ethanol, 1:1 glycerol:ethanol, and triethanolamine between 25 and 295 K. Although the dominant process changes with temperature, relaxation rates vary smoothly with temperature, even near the glass transition temperatures, and could be modeled as the sum of contributions that have the temperature dependence that is predicted for the direct, Raman, local mode and tumbling dependent processes. At 85 K, which is in a temperature range where the Raman process dominates, relaxation rates along the gxx (g~2.006) and gyy (g~2.005) axes are about 2.7 to 1.5 times faster than along the gzz axis (g = 2.0023). In highly viscous triethanolamine, contributions from tumbling-dependent processes are negligible. At temperatures above 100 K relaxation rates in triethanolamine are unchanged between X-band (9.5 GHz) and Q-band (34 GHz), so the process that dominates in this temperature interval was assigned as a local mode rather than a thermally-activated process. Because the largest proton hyperfine couplings are only 2.2 G, spin rotation makes a larger contribution than tumbling-dependent modulation of hyperfine anisotropy. Since g anisotropy is small, tumbling dependent modulation of g anisotropy make a smaller contribution than spin rotation at X-band. Although there was negligible impact of methyl rotation on T1, rotation of t-butyl or t-amyl methyl groups enhances spin echo dephasing between 85 and 150 K.

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Flavoenzyme catalysed oxidation of amines: roles for flavin and protein-based radicals

Cited by 16 publications

References 44 publications

Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves

Serotonin produces monoamine oxidase-dependent oxidative stress in human heart valves

Intrigues and Intricacies of the Biosynthetic Pathways for the Enzymatic Quinocofactors: PQQ, TTQ, CTQ, TPQ, and LTQ

Electron spin relaxation rates for semiquinones between 25 and 295K in glass-forming solvents

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