Bioenergetics and Oxidative Phosphorylation PDF

BIOCHEMISTRY Dersin Alt Konusu: Bioenergetics and Oxidative Phosphorylation-I Dersin Sorumlusu: Prof Dr Metin YILDIRIMKAYA Online Ders Materyalleri Overview Bioenergetics: describes t...

BIOCHEMISTRY Dersin Alt Konusu: Bioenergetics and Oxidative Phosphorylation-I Dersin Sorumlusu: Prof Dr Metin YILDIRIMKAYA Online Ders Materyalleri Overview Bioenergetics: describes the transfer and utilization of energy in biologic systems and concerns the initial and final energy states of the reaction components. Because changes in free energy provide a measure of the energetic feasibility of a chemical reaction, they allow prediction of whether a reaction or process can take place. In short, bioenergetics predicts if a process is possible, whereas kinetics measures the reaction rate. Overview Adenosine triphosphate (ATP) transfers energy from the processes that produce it to those that use it. Most carbons of glucose, fatty acids, glycerol, and amino acids are ultimately converted to acetyl-CoA. ATP is produced by these reactions. Acetyl-CoA is oxidized in the tricarboxylic acid (TCA) cycle. CO2 is released, and electrons are passed to NAD+ and FAD, producing NADH and FADH2. NADH and FADH2 transfer the electrons to O2 via the electron transport chain. Energy from this transfer of electrons is used to produce ATP by the process of oxidative phosphorylation. Cofactors, many of which are minerals or compounds produced from vitamins, aid the enzymes that catalyze the reactions of these metabolic pathways. The generation of adenosine triphosphate (ATP) from fuels in the blood, and cellular respiration Bioenergetics: The Role of ATP Bioenergetics, or biochemical thermodynamics, is the study of the energy changes accompanying biochemical reactions. Biologic systems are essentially isothermic and use chemical energy to power living processes. Animal obtains suitable fuel from its food to provide this energy is basic to the understanding of normal nutrition and metabolism. Death from starvation occurs when available energy reserves are depleted, and certain forms of malnutrition are associated with energy imbalance (marasmus). Thyroid hormones control the metabolic rate (rate of energy release), and disease results if they malfunction. Excess storage of surplus energy causes obesity, an increasingly common disease of Western society which predisposes to many diseases, including cardiovascular disease and diabetes mellitus type 2, and lowers life expectancy. Free energy is the useful energy in a system Free energy (ΔG) is that portion of the total energy change in a system that is available for doing work useful energy, chemical potential. General Laws of Thermodynamics 1. The first law of thermodynamics states that the total energy of a system, including its surroundings, remains constant. Within the total system, energy is neither lost nor gained during any change. However, energy may be transferred from one part of the system to another, or may be transformed into another form of energy. In living systems, chemical energy may be transformed into heat or into electrical, radiant, or mechanical energy. General Laws of Thermodynamics /cont’) 2. The second law of thermodynamics states that the total entropy of a system must increase if a process is to occur spontaneously. Entropy is the extent of disorder or randomness of the system and becomes maximum as equilibrium is approached. Under conditions of constant temperature and pressure, the relationship between the free-energy change (ΔG) of a reacting system and the change in entropy (ΔS) is expressed by the following equation, which combines the two laws of thermodynamics: (Useful energy = change in enthalpy – change in entropy) where ΔH is the change in enthalpy (heat-energy content) and T is the absolute temperature in Kelvin.  If ΔG is negative, the reaction proceeds spontaneously with loss of free energy, that is, it is exergonic. If ΔG is positive, the reaction proceeds only if free energy can be gained, that is, it is endergonic. If ΔG is zero, the system is at equilibrium and no net change takes place. Free energy change The change in free energy is represented in two ways: ΔG and ΔG0. ΔG (without the superscript “0”), represents the change in free energy and, thus, the direction of a reaction at any specified concentration of products and reactants. ΔG, is a variable. The standard free energy change, ΔG0 (with the superscript “0”), is the energy change when reactants and products are at a concentration of 1 mol/l at pH = 7. This may be shown by a prime sign [ ′ ] , e.g., ΔG0′ Although ΔG0, a constant, represents energy changes at these nonphysiologic concentrations of reactants and products, it is nonetheless useful in comparing the energy changes of different reactions. Furthermore, ΔG0 can readily be determined from measurement of the equilibrium constant. ΔG and reaction direction The sign of ΔG can be used to predict the direction of a reaction at constant temperature and pressure. Consider the reaction: A⇄B If ΔG is negative, the reaction is considered exergonic with a net loss of energy. In this case, the reaction proceeds spontaneously as written, with A converted to B (Fig. A). If ΔG is positive, the reaction is endergonic with a net gain of energy. Energy must be added to the system in order for the reaction from B to A to take place (Fig. B). In cases where ΔG = 0, the reaction is in equilibrium. Note that when a reaction is proceeding spontaneously (ΔG is negative), the reaction will continue until ΔG reaches zero and equilibrium is established. ΔG and reactant and product concentrations The ΔG of the reaction A → B depends on the concentrations of the reactant and of the product. At constant temperature and pressure, the following relationship can be derived: ΔG = ΔG0 + RTIn[B] / [A] ΔG0 is the standart free energy change R is the gas constant (1.987 cal/mol K) T is the absolute temperature (K) [A] and [B] are the actual concentrations of the reactant and product ln represents the natural logarithm. A reaction with a positive ΔG0 can proceed in the forward direction if the ratio of products to reactants ([B]/[A]) is sufficiently small (i.e., the ratio of reactants to products is large) to make ΔG negative. ΔG and reactant and product concentrations For example, consider the reaction: Glucose 6-phosphate ⇄ fructose 6-phosphate Figure shows reaction conditions in which the concentration of reactant, glucose 6-phosphate, is high compared with the concentration of product, fructose 6- phosphate. This means that the ratio of the product to reactant is small, and RT ln([fructose 6-phosphate]/[glucose 6- phosphate]) is large and negative, causing ΔG to be negative despite ΔG0 being positive. Thus, the reaction can proceed in the forward direction. Standard free energy change (ΔG0) The standard free energy change, ΔG0, is equal to the free energy change, ΔG, under standard conditions, when reactants and products are at 1 mol/l concentrations (Fig. B). Under these conditions, the natural logarithm of the ratio of products to reactants is zero (ln1 = 0), and, therefore, the equation shown at the bottom of the previous page becomes: ΔG = ΔG0 + 0 ΔG0 and reaction direction: Under standard conditions, ΔG0 can be used to predict the direction a reaction proceeds because, under these conditions, ΔG0 is equal to ΔG. However, ΔG0 cannot predict the direction of a reaction under physiologic conditions because it is composed solely of constants (R, T, and Keq) and is not, therefore, altered by changes in product or substrate concentrations. Relationship between ΔG0 and Keq: In a reaction A ⇄ B, a point of equilibrium is reached at which no further net chemical change takes place. In this state, the ratio of [B] to [A] is constant, regardless of the actual concentrations of the two compounds: Keq = [B] / [A] where Keq is the equilibrium constant, and [A]eq and [B]eq are the concentrations of A and B at equilibrium. If the reaction A ⇄ B is allowed to reach equilibrium at constant temperature and pressure, then, at equilibrium, the overall ΔG is zero (Fig. C). Cont’ Negative Positive Endergonic processes proceed by coupling to exergonic processes The vital processes—for example, synthetic reactions, muscular contraction, nerve impulse conduction, and active transport—obtain energy by chemical linkage, or coupling, to oxidative reactions. The conversion of metabolite A to metabolite B occurs with release of free energy and is coupled to another reaction in which free energy is required to convert metabolite C to metabolite D. The terms exergonic (loss of free energy) and endergonic (gain of free energy) In practice, an endergonic process cannot exist independently, but must be a component of a coupled exergonic– endergonic system where the overall net change is exergonic. The exergonic reactions are termed catabolism (generally, the breakdown or oxidation of fuel molecules), whereas the synthetic reactions that build up substances are termed anabolism. The combined catabolic and anabolic processes constitute metabolism. Coupling of an exergonic to an endergonic reaction Properties of Adenosine Triphosphate ATP contains the base adenine, the sugar ribose, and three phosphate groups joined to each other by two anhydride bonds. ATP is produced from adenosine diphosphate (ADP) and inorganic phosphate (Pi) mainly by the process of oxidative phosphorylation. The free energy released when ATP is hydrolyzed is used to drive reactions that require energy. ATP can transfer phosphate groups to other compounds such as glucose, forming ADP. ADP can accept phosphate groups from compounds such as phosphocreatine, forming ATP.  In the living cell, the principal high-energy intermediate or carrier compound is ATP 1.ATP consists of the base adenine, the sugar ribose, and three phosphate groups 1. Adenosine (a nucleoside) contains the base adenine linked to ribose. 2. Adenosine monophosphate (AMP) is a nucleotide that contains adenosine with a phosphate group esterified to the 5′- hydroxyl of the sugar. 3. ADP contains a second phosphate group attached by an anhydride bond. 4. ATP contains a third phosphate group. High-energy phosphates play a central role in energy capture and transfer In all organisms, ATP plays a central role in the transference of free energy from the exergonic to the endergonic processes. ATP is a nucleotide consisting of the nucleoside adenosine (adenine linked to ribose) and three phosphate groups. In its reactions in the cell, it functions as the Mg2+ complex The functions of ATP ATP plays a central role in energy exchanges in the body 1. ATP is constantly being consumed and regenerated 2. The free energy released when ATP id hydrolysed is used to drive reactionsthat require energy - ATP can be hydrolyzed to ADP and Pi or to AMP and pyrophosphate (PPi). ATP, ADP and AMP are interconverted by the adenylate kinase reaction ATP + AMP ⇆ 2 ADP 3. For the hydrolysis of ATP to ADP and Pi, ΔG0 = -7.3 kcal/mol 4. ATP can transfer phosphate groups to compounds such as glucose, forming ADP 5. ADP can ccept phosphate groups from compounds such as phosphoenolpyruvate, phosphocreatine, or 1,3-bisphosphoglycerate, forming ATP Standard Free Energy of Hydrolysis of Some Organophosphates of Biochemical Importance Structure of ATP, ADP, and AMP showing the position and the number of high-energy phosphates (~℗) Other “high-energy compounds” Coenzyme A (eg, acetyl-CoA), (thiol esters) Acyl carrier protein, (thiol esters) Amino acid esters involved in protein synthesis, S-adenosylmethionine (active methionine), Uridine diphosphate glucose (UDPGlc), and 5- phosphoribosyl-1-pyrophosphate (PRPP). The free-energy change on hydrolysis of ATP to ADP The high group transfer potential of ATP enables it to act as a donor of high-energy phosphate to form those compounds below it in Table. Likewise, with the necessary enzymes, ADP can accept phosphate groups to form ATP from those compounds above ATP in the table. Role of ATP/ADP cycle in transfer of high-energy phosphate There are three major sources of ~℗ taking part in energy conservation or energy capture: 1. Oxidative phosphorylation is the greatest quantitative source of ~℗ in aerobic organisms. ATP is generated in the mitochondrial matrix as O2 is reduced to H2O by electrons passing down the respiratory chain 2. Glycolysis. A net formation of two ~℗ results from the formation of lactate from one molecule of glucose, generated in two reactions catalyzed by phosphoglycerate kinase and pyruvate kinase, respectively 3. The citric acid cycle. One ~℗ is generated directly in the cycle at the succinate thiokinase step Phosphagens act as storage forms of group transfer potential and include creatine phosphate, which occurs in vertebrate skeletal muscle, heart, spermatozoa, and brain When ATP is rapidly being utilized as a source of energy for muscular contraction, phosphagens permit its concentrations to be maintained, but when the ATP/ADP ratio is high, their concentration can increase to act as an energy store Transfer of high-energy phosphate between ATP and creatine. https://www.youtube.com/watch?v=vnw76pfiteQ https://www.youtube.com/watch?v=nDCxIpiI7-Y https://www.youtube.com/watch?v=5GMLIMIVUvo THANK YOU FOR LISTENING Online Ders Materyalleri