Biomedical Importance Oxidation: defined as the removal of electrons Reduction is the gain of electrons This principle of oxidation-reduction applies equally biochemical systems and is an important concept underlying understanding of the nature biologic oxidation. Molecular oxygen is incorporated into variety of enzymes designated as oxygenases Drugs, pollutants, and chemical carcinogens (xenobiotics) Metabolized by enzymes of this class→ known as the cytochrome P450 system Free energy changes can be expressed in terms of redox potential In oxidation and reduction- free energy change is proportionate to the tendency of reactants to donate or accept electrons Simply saying: that redox potential is like a potential for molecules to acquire electrons→ thereby getting reduced. Redox potential E0 compared with the potential of the hydrogen electron (0.0 volts at pH 0.0) Expressed at pH 7.0 which pH the electrode potential of the hydrogen electrode is -0.42 volts Oxidoreductases: Enzymes involved in oxidation and reduction Oxidases Dehydrogenases Hydroperoxidases Oxygenases Oxidase use oxygen as hydrogen acceptor Oxidases→ catalyze removal of hydrogen from a substrate using oxygen as a hydrogen acceptor They form water or hydrogen peroxide as a reaction Cytochrome Oxidase→ hemoprotein seen in myoglobin and hemoglobin→ component chain of respiratory carriers found in mitochondria. Flavoproteins→ enzymes that contain flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD) are formed in the body from riboflavin → seen in Dehydrogenases → cannot use oxygen as a hydrogen acceptor→ utilized in NAD+ and oxidative phosphorylation Use nicotinamide dinucleotide (NAD+) nicotinamide dinucleotide phosphate (formed from niacin) NADH dehydrogenase acts as a carrier of electrons between NADH and components of other redox potential Others such as succinate dehydrogenase, acyl-CoA dehydrogenase, mitochondrial glycer 3 phosphate transfer reducing equivalents directly from the substrate to the respiratory chain The electron-transferring flavoprotein is an intermediary carrier of electrons between acyl-CoA dehydrogenase and the respiratory chain. Cytochromes→ iron containing hemoproteins (iron atom switches between ferric (Fe3+) and ferrous (Fe2+) Except for cytochrome oxidase: classified as dehydrogenases-> involved in respiratory chain as carriers of electrons from flavoproteins on the one hand to cytochrome oxidase on the other THE RESPIRATORY CHAIN AND OXIDATIVE PHOSPHORYLATION Aerobic organisms are able to capture a far greater energy than anaerobic organisms. All takes places inside the mitochondria (“the powerhouses”) Respiration is coupled to the generation of ATP by oxidative phosphorylation.
Inhibitors of Phosphorylation Effects of Mitochondrial Defects
Amobarbital
Cyanide
Carbon monoxide Myopathy
Encelopathy
Lactic acidosis Enzymes act as markers Mitochondrial Outer membrane: Permeable to most metabolites Presence of enzymes: Acyl CoA synthetase Glycophosphate acyltransferase Intermembrane space Enzymes: Adenylyl kinase Creatine kinase Inner membrane Enclosing a matrix within the mitochondria Phospholipid cardiolipin is concentrated in the inner membrane Enzymes of the respiratory chain ATP synthase Membrane transporters Respiratory Chain Oxides Reducing Equivalents Most of the energy liberated during oxidation of the carbs, fatty acids, and amino acids are made available within the mitochondria as reducing equivalents (-H or electrons) Enzymes of the citric acid cycle and Beta-oxidation are contained within the mitochondria Together with the respiratory chain→ Collects, transports reducing equivalents Direct them to their final reaction with oxygen to form water Drive the process by which liberated energy is trapped as high energy phosphate Components of the Chain: Four Large Protein Complexes in the Inner