Cellular Energy Transactions: Role of Mitochondria Cells can derive useful energy from fermentation processes like glycolysis

plus the reduction of pyruvate to lactic acid. Most cells, however, oxidize their organic food stuffs completely to CO, and H,0. By doing so, they extract much more of the available energy from each-food molecule. The oxidation of organic molecules in eukaryotic cells is completed in the mitochondrion. Mitochondria are thought to have evolved from prokaryotes that established a symbiotic relationship with a primitive eukaryotic cell. Mitochondria Mitochondrion is a structure found in most eukaryotic cells, including plant cells, algae and protozoans (except mature mammalian RBC). Mitochondria are composed of two membranes, the outer membrane covers the organelle and the inner membrane is thrown into folds, the cristae that penetrate the matrix. In lower forms such as Protozoa and in the adrenal cortex of mammals, the folds of the inner membrane form tubules, whereas in the cells of other animals and plants, they form flattened vesicles. The inner membrane encloses the amorphous material known as matrix and a variety of electron dense granules. Mitochondria contain DNA, which is partially duplicating organelle. The DNA of the mitochondrion contains only a small part of the hereditary information necessary for replication and growth, the remainder is found in the nuclear DNA. The inner membrane exhibits selectivity over what materials are allowed through it and it is known that active transport mechanisms involving translocase enzymes are responsible for the movement of ADP and ATP across it. Negative staining techniques indicate the presence of elementary particles on the matrix side of the inner membrane. The particles are projected out from the membrane into the matrix. The headpiece is associated with ATP synthesis and a coupling enzyme, ATPase (F, particle) that acts to link the phosphorylation of ADP to the respirator) chain. At the base of the particle, and extending through the inner membrane, are the components of the respiratory chain itself. They are arranged in precise positions relative to each other. The mitochondrial matrix contains most of the enzymes controlling the Krebs cycle and fatty acid oxidation. In addition, mitochondrial DNA, RNA and ribosomes are present as well as a variety of small proteins. Electron Transport Chain Energy-rich molecules, such as glucose or fatty acids are metabolized by a series of oxidation reactions yielding CO2, and H20. The metabolic intermediates of these reactions donate electrons to specialized coenzymes, nicotinamide adenine dinucleotide (NAD*) and flavin adenine dinucleotide (FAD), to form the energy rich reduced coenzymes NADH and FADH2. These

reduced coenzymes can, in turn, donate a pair of electrons to a specialized set of electron carriers, collectively known as the electron transport chain. As electrons are passed down the electron transport chain, they lose much of their free energy. Part of this energy can be captured and stored by the production of ATP from ADP and inorganic phosphate (Pi). This process is called oxidative phosphorylation. The remainder of the free energy not trapped as ATP is released as heat. Organization of the Chain The Inner mitochondrial membrane can be disrupted into five separate enzyme complexes called complex I, II, III, IV and V. Complexes I to IV each contain part of the electron transport chain whereas complex V catalyzes ATP synthesis. Each complex accepts or donates electrons to relatively mobile electron carriers. Such as coenzyme and cytochrome C. Each carrier of the electron transport chain can receive electrons from an electron donor and can subsequently donate electron to the next carrier in the chain, ultimately to combine with oxygen and protons to form water. This requirement for oxygen makes the electron transport process the respiratory chain, which accounts for the greatest portion of the bodys utilization of oxygen. Reactions of the ET Chain With the exception of coenzyme all members of this chain are proteins. These may function as enzymes as is the case with the various dehydrogenases, may contain iron as part of an iron sulfur center, be coordinated with a porphyrin ring as in the cytochromes or may contain copper as in cytochrome a+a3, 1. Formation of NADH-NAD+ is reduced to NADH by dehydrogenases, which remove two hydrogen atoms from their substrate. Both electrons put only one proton (that is, a hydride ion,: H) are transferred to the NAD* forming NADH plus a free proton H+, which is released into the medium. The free proton plus the hydride ion carried by NADH are next transferred to NADH dehydrogenase, an enzyme complex embedded in the inner mitochondrial membrane. This complex has a tightly bound molecule of flavin mononuleotide (FMN), that accepts the two hydrogen atoms (2e+ +2H+), becoming FMNH2, NADH dehydrogenase also contain several iron atoms paired with sulfur atoms to make iron-sulfur centers. These are necessary for the transfer of the hydrogen atoms lo the next member of the chain, i.e. ubiquinone coenzyme Q). Coenzyme Q is a quinone derivative with a long isoprenoil tail. It can accept hydrogen atoms both from FMNI produced by NADH dehydrogenase, and from FADH. which is produced by succinate dehydrogenase and acetyl CoA dehydrogenase. Cytochromes - The remaining member of the ET chain are cytochromes. Each contains a heme group made up of a porphyrin ring containing an atom of iron.

Unlike the heme groups of Hb., the cytochrome iron atom is reversibly converted from its ferric (Fe 3+) to its ferrous (Fe 2+) form as a normal part of its function i.e. a reversible carrier of electrons. Electrons are passed down the chain from coenzyme Q to cyt b, c and a+a3. Cyt a+a3- This cytochrome is the only electron carrier in which the heme iron has a free legend that can react directly with molecular oxygen. At this site the transported elections, molecular oxygen and free protons are brought together to produce water. 2. Oxidative Phosphorylation Electron transport is coupled to transport of protons (H+)across the inner mitochondrial membrane from the matrix to intermembrane space. This process creates an electrical gradient (with more +ve charges on the outside of the membrane than on the inside) and a pH gradient (the outside of the membrane is at a lower pH than the inside. The energy generated by this proton gradient is sufficient to drive ATP synthesis (explained by chemiosmotic hypothesis also known as Mitchell Hypothesis). The enzyme complex ATP synthetase (complex V) synthesizes ATP, utilizing the energy of the proton gradient generated by the electron transport chain. The chemiosmotic hypothesis propose that after protons have been transferred to the cytosolic side of the inner mitochondria membrane, they can re-enter the mitochondrial matrix by passing through a channel in the ATP synthetase molecule, resulting in the synthesis of ATP from ADP+Pi and the same time dissipating the pH and electrical gradient.