RESUMO
Colin Allen Wraight (1945-2014) was a well-known biophysicist and biochemist of our times-formerly Professor of Biochemistry, Biophysics and Plant Biology, and Head of the Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, USA. (See a detailed Tribute to him by Govindjee et al., Photosynth Res, 2015.) During the latter part of his life, Colin had (1) given an excellent lecture in 2008 on the overall topic of the molecular mechanisms in biological energy conversion, focusing on how an ubiquinone is reduced to ubiquinol at the so-called "two electron gate", and (2) presented a review poster on the design features of long distance proton transport in biological systems, with focus on photosynthetic bacteria (a pdf file of the original is available from one of us, Govindjee). We present here for historical purpose, a complete transcript of his 2008 lecture and his 2013 poster, which have been annotated and expanded by the authors of this paper. The major theme is: electron and proton transfer in biological systems, with emphasis on bacterial reaction centers. The figures, some of which were prepared by us, are presented in sequence for both the lecture and the poster. A common bibliography is provided at the end of the paper, which is divided into two parts: (I) The Lecture; and (II) The Poster.
Assuntos
Bactérias/metabolismo , Transferência de Energia , Fotossíntese , Transporte de Elétrons , Metabolismo Energético , Modelos MolecularesRESUMO
Statins are the first line treatment for the management of hyperlipidemia. However, the primary adverse effect limiting their use is myopathy. This study examines the efficacy and safety of red yeast rice (RYR), a source of natural statins, as compared with atorvastatin, which is the most widely used synthetic statin. Statin interference with the endogenous synthesis of coenzyme Q10 (CoQ10) prompted the hypothesis that its deficiency may be implicated in the pathogenesis of statin-associated myopathy. Hence, the effects of combination of CoQ10 with either statin have been evaluated. Rats were rendered hyperlipidemic through feeding them a high-fat diet for 90 days, during the last 30 days of the diet they were treated daily with either atorvastatin, RYR, CoQ10, or combined regimens. Lipid profile, liver function tests, and creatine kinase were monitored after 15 and 30 days of drug treatments. Heart contents of CoQ9 and CoQ10 were assessed and histopathological examination of the liver and aortic wall was performed. RYR and CoQ10 had the advantage over atorvastatin in that they lower cholesterol without elevating creatine kinase, a hallmark of myopathy. RYR maintained normal levels of heart ubiquinones, which are essential components for energy production in muscles. In conclusion, RYR and CoQ10 may offer alternatives to overcome atorvastatin-associated myopathy.
Assuntos
Produtos Biológicos/uso terapêutico , Ácidos Heptanoicos/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Doenças Musculares/induzido quimicamente , Pirróis/efeitos adversos , Ubiquinona/análogos & derivados , Animais , Aorta/efeitos dos fármacos , Aorta/patologia , Atorvastatina , Produtos Biológicos/administração & dosagem , Terapia Combinada , Creatina Quinase/sangue , Dieta Hiperlipídica , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Lipoproteínas/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Doenças Musculares/complicações , Doenças Musculares/metabolismo , Miocárdio/metabolismo , Pirróis/uso terapêutico , Ratos , Ubiquinona/administração & dosagem , Ubiquinona/metabolismo , Ubiquinona/uso terapêuticoRESUMO
The interaction of dietary fats and carbohydrates on liver mitochondria were examined in male FBNF1 rats fed 20 different low-fat isocaloric diets. Animal growth rates and mitochondrial respiratory parameters were essentially unaffected, but mass spectrometry-based mitochondrial lipidomics profiling revealed increased levels of cardiolipins (CLs), a family of phospholipids essential for mitochondrial structure and function, in rats fed saturated or trans fat-based diets with a high glycemic index. These mitochondria showed elevated monolysocardiolipins (a CL precursor/product of CL degradation), elevated ratio of trans-phosphocholine (PC) (18:1/18:1) to cis-PC (18:1/18:1) (a marker of thiyl radical stress), and decreased ubiquinone Q9; the latter two of which imply a low-grade mitochondrial redox abnormality. Extended analysis demonstrated: i) dietary fats and, to a lesser extent, carbohydrates induce changes in the relative abundance of specific CL species; ii) fatty acid (FA) incorporation into mature CLs undergoes both positive (>400-fold) and negative (2.5-fold) regulation; and iii) dietary lipid abundance and incorporation of FAs into both the CL pool and specific mature tetra-acyl CLs are inversely related, suggesting previously unobserved compensatory regulation. This study reveals previously unobserved complexity/regulation of the central lipid in mitochondrial metabolism.
Assuntos
Cardiolipinas/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Ácidos Graxos Ômega-6/metabolismo , Mitocôndrias Hepáticas/metabolismo , Animais , Respiração Celular , Dieta , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Índice Glicêmico , Fígado/metabolismo , Masculino , Estresse Oxidativo , Consumo de Oxigênio , Ratos , Ubiquinona/metabolismoRESUMO
The data presented indicate that there is a variety of unique prenyllipids, often of very limited taxonomic distribution, whose origin, biosynthesis, metabolism and biological function deserves to be elucidated. These compounds include tocoenols, tocochromanol esters, tocochromanol acids, plastoquinones and ubiquinones. Additionally, based on the available data, it can be assumed that there are still unrecognized prenyllipids, like prenylquinols fatty acid esters of the hydroquinone ring, including prenylquinol phosphates, and others, whose biological function might be of great importance. Our knowledge of these compounds is not only important from the scientific point of view, but may also be of practical significance to medicine, pharmacy or cosmetics.