Synthesis and characterization of mitoQ and idebenone analogues as mediators of oxygen consumption in mitochondria.
Summary of "Synthesis and characterization of mitoQ and idebenone analogues as mediators of oxygen consumption in mitochondria."
Analogues of mitoQ and idebenone were synthesized to define the structural elements that support oxygen consumption in the mitochondrial respiratory chain. Eight analogues were prepared and fully characterized, then evaluated for their ability to support oxygen consumption in the mitochondrial respiratory chain. While oxygen consumption was strongly inhibited by mitoQ analogues 2-4 in a chain length-dependent manner, modification of idebenone by replacement of the quinone methoxy groups by methyl groups (analogues 6-8) reduced, but did not eliminate, oxygen consumption. Idebenone analogues 6-8 also displayed significant cytoprotective properties toward cultured mammalian cells in which glutathione had been depleted by treatment with diethyl maleate.
Affiliation
Center for BioEnergetics, Biodesign Institute, and Department of Chemistry, Arizona State University, Tempe, AZ 85287, USA.
Journal Details
This article was published in the following journal.
Name: Bioorganic & medicinal chemistry
ISSN: 1464-3391
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20691600
- DOI: http://dx.doi.org/10.1016/j.bmc.2010.06.104
Medical and Biotech [MESH] Definitions
Oxygen Consumption
The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)
Metabolic Equivalent
A measurement of OXYGEN uptake in a sitting, resting person (resting oxygen consumption), varying with age, sex, race, and other factors. In normal adult men, one MET is approximately 3.5 ml O2/kg/min of body weight. Oxygen uptake during activities or work can be measured in METs which can be use to determine health status and exercise prescription.
Enoximone
1,3-Dihydro-4-methyl-5-(4-(methylthio)benzoyl)-2H-imidazol-2-one. A selective phosphodiesterase inhibitor with vasodilating and positive inotropic activity that does not cause changes in myocardial oxygen consumption. It is used in patients with congestive heart failure.
Anaerobic Threshold
The oxygen consumption level above which aerobic energy production is supplemented by anaerobic mechanisms during exercise, resulting in a sustained increase in lactate concentration and metabolic acidosis. The anaerobic threshold is affected by factors that modify oxygen delivery to the tissues; it is low in patients with heart disease. Methods of measurement include direct measure of lactate concentration, direct measurement of bicarbonate concentration, and gas exchange measurements.
Anti-allergic Agents
Agents that are used to treat allergic reactions. Most of these drugs act by preventing the release of inflammatory mediators or inhibiting the actions of released mediators on their target cells. (From AMA Drug Evaluations Annual, 1994, p475)
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