Role of ATP PDF

Biochemistry Bioenergetics The Role of ATP The Role of ATP Biomedical Importance: 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. How an...

Biochemistry Bioenergetics The Role of ATP The Role of ATP Biomedical Importance: 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. How an 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). The Role of ATP Biomedical Importance: Thyroid hormones control the rate of energy release (metabolic rate), and disease results when they malfunction. Excess storage of surplus energy causes obesity, one of the most common diseases of Western society. The Role of ATP Free Energy is the Useful Energy in a System: Gibbs change in free energy (ΔG) is that portion of the total energy change in a system that is available for doing work, ie, the useful energy, also known as the chemical potential. The Role of ATP Biologic Systems Conform to the General Laws of Thermodynamics: The first law of thermodynamics states that the total energy of a system, including its surroundings, remains constant. It implies that 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. The Role of ATP Biologic Systems Conform to the General Laws of Thermodynamics: 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: ∆𝐺 = ∆𝐻 − 𝑇∆𝑆 The Role of ATP Biologic Systems Conform to the General Laws of Thermodynamics: Where ΔH is the change in enthalpy (heat) and T is the absolute temperature. In biochemical reactions, because ΔH is approximately equal to ΔE, the total change in internal energy of the reaction, the above relationship may be expressed in the following way: ∆𝐺 = ∆𝐸 − 𝑇∆𝑆 If ΔG is negative, the reaction proceeds spontaneously with loss of free energy; ie, it is exergonic. If, in addition, ΔG is of great magnitude, the reaction goes virtually to completion and is essentially irreversible. The Role of ATP Biologic Systems Conform to the General Laws of Thermodynamics: On the other hand, if ΔG is positive, the reaction proceeds only if free energy can be gained, i.e., it is endergonic. If, in addition, the magnitude of ΔG is great, the system is stable, with little or no tendency for a reaction to occur. If ΔG is zero, the system is at equilibrium and no net change takes place. When the reactants are present in concentrations of 1.0 mol/L, ΔG0 is the standard free energy change. For biochemical reactions, a standard state is defined as having a pH of 7.0. The standard free energy change at this standard state is denoted by ΔG0′. The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: The vital processes—e.g., synthetic reactions, muscular contraction, nerve impulse conduction, and active transport—obtain energy by chemical linkage, or coupling, to oxidative reactions. In its simplest form, this type of coupling may be represented as shown in Figure 1. 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 and endergonic, rather than the normal chemical terms "exothermic" and "endothermic," are used to indicate that a process is accompanied by loss or gain, respectively, of free energy in any form, not necessarily as heat. The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: 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. The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: If the reaction shown in Figure 1 is to go from left to right, then the overall process must be accompanied by loss of free energy as heat. One possible mechanism of coupling could be envisaged if a common obligatory intermediate (I) took part in both reactions, i.e., 𝐴+𝐶 →𝐼 →𝐵+𝐷 Some exergonic and endergonic reactions in biologic systems are coupled in this way. The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: Figure 1 – : Coupling of an exergonic to an endergonic reaction. The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: This type of system has a built-in mechanism for biologic control of the rate of oxidative processes since the common obligatory intermediate allows the rate of utilization of the product of the synthetic path (D) to determine by mass action the rate at which A is oxidized. Indeed, these relationships supply a basis for the concept of respiratory control, the process that prevents an organism from burning out of control. An extension of the coupling concept is provided by dehydrogenation reactions, which are coupled to hydrogenations by an intermediate carrier (Figure 2). The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: Figure 2 – : Coupling of dehydrogenation and hydrogenation reactions by an intermediate carrier. The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: An alternative method of coupling an exergonic to an endergonic process is to synthesize a compound of high-energy potential in the exergonic reaction and to incorporate this new compound into the endergonic reaction, thus effecting a transference of free energy from the exergonic to the endergonic pathway (Figure 3). The biologic advantage of this mechanism is that the compound of high potential energy, ~Ⓔ , unlike I in the previous system, need not be structurally related to A, B, C, or D, allowing Ⓔ to serve as a transducer of energy from a wide range of exergonic reactions to an equally wide range of endergonic reactions or processes, such as biosynthesis, muscular contraction, nervous excitation, and active transport. The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: Figure 3 – : Transfer of free energy from an exergonic to an endergonic reaction via a high-energy intermediate compound (~.Ⓔ) The Role of ATP Endergonic Processes Proceed by Coupling to Exergonic Processes: In the living cell, the principal high-energy intermediate or carrier compound (designated ~Ⓔ in Figure 3) is adenosine triphosphate (ATP) (Figure 4). Figure 4 The Role of ATP High-Energy Phosphates Play a Central Role in Energy Capture and Transfer: In order to maintain living processes, all organisms must obtain supplies of free energy from their environment. Autotrophic organisms utilize simple exergonic processes; e.g., the energy of sunlight (green plants), the reaction Fe2+ to Fe3+ (some bacteria). On the other hand, heterotrophic organisms obtain free energy by coupling their metabolism to the breakdown of complex organic molecules in their environment. In all these organisms, ATP plays a central role in the transference of free energy from the exergonic to the endergonic processes (Figure 3). The Role of ATP High-Energy Phosphates Play a Central Role in Energy Capture and Transfer: ATP is a nucleoside triphosphate containing adenine, ribose, and three phosphate groups. In its reactions in the cell, it functions as the Mg2+ complex (Figure 4). Figure 4 The Role of ATP The Intermediate Value for the Free Energy of Hydrolysis of ATP Has Important Bioenergetic Significance: The standard free energy of hydrolysis of a number of biochemically important phosphates is shown in Table 1. An estimate of the comparative tendency of each of the phosphate groups to transfer to a suitable acceptor may be obtained from the ΔG0' of hydrolysis at 37°C. The value for the hydrolysis of the terminal phosphate of ATP divides the list into two groups. Low-energy phosphates, exemplified by the ester phosphates found in the intermediates of glycolysis, have G0' values smaller than that of ATP, while in highenergy phosphates the value is higher than that of ATP. The Role of ATP The Intermediate Value for the Free Energy of Hydrolysis of ATP Has Important Bioenergetic Significance: Table 1 The Role of ATP The Intermediate Value for the Free Energy of Hydrolysis of ATP Has Important Bioenergetic Significance: The components of this latter group, including ATP, are usually anhydrides (e.g., the 1phosphate of 1,3-bisphosphoglycerate), enolphosphates (e.g., phosphoenolpyruvate), and phosphoguanidines (e.g., creatine phosphate, arginine phosphate). The symbol ~Ⓔ indicates that the group attached to the bond, on transfer to an appropriate acceptor, results in transfer of the larger quantity of free energy. For this reason, the term group transfer potential, rather than "high-energy bond," is preferred by some. The Role of ATP The Intermediate Value for the Free Energy of Hydrolysis of ATP Has Important Bioenergetic Significance: Thus, ATP contains two high-energy phosphate groups and ADP contains one, whereas the phosphate in AMP (adenosine monophosphate) is of the low-energy type since it is a normal ester link (Figure 5). Figure 5 The Role of ATP The Intermediate Value for the Free Energy of Hydrolysis of ATP Has Important Bioenergetic Significance: The intermediate position of ATP allows it to play an important role in energy transfer. The high free-energy change on hydrolysis of ATP is due to relief of charge repulsion of adjacent negatively charged oxygen atoms and to stabilization of the reaction products, especially phosphate, as resonance hybrids (Figure 6). Other "high-energy compounds" are thiol esters involving coenzyme A (e.g., acetylCoA), acyl carrier protein, amino acid esters involved in protein synthesis, Sadenosylmethionine (active methionine), UDPGlc (uridine diphosphate glucose), and PRPP (5-phosphoribosyl-1-pyrophosphate). The Role of ATP Figure 6 The Role of ATP High-Energy Phosphates Act as the "Energy Currency" Of The Cell: ATP is able to act as a donor of high-energy phosphate to form those compounds below it in Table 1. Likewise, with the necessary enzymes, ADP can accept high-energy phosphate to form ATP from those compounds above ATP in the table. In effect, an ATP/ADP cycle connects those processes that generate ~℗ to those processes that utilize ~℗ (Figure 7), continuously consuming and regenerating ATP. This occurs at a very rapid rate since the total ATP/ADP pool is extremely small and sufficient to maintain an active tissue for only a few seconds. The Role of ATP Figure 7 – : Role of ATP/ADP cycle in transfer of high-energy phosphate. The Role of ATP High-Energy Phosphates Act as the "Energy Currency" Of The Cell: There are three major sources of ~℗ taking part in energy conservation or energy capture: 1. Oxidative phosphorylation: The greatest quantitative source of ~℗ in aerobic organisms. Free energy comes from respiratory chain oxidation using molecular O2 within mitochondria. 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. The Role of ATP High-Energy Phosphates Act as the "Energy Currency" Of The Cell: Phosphagens act as storage forms of high-energy phosphate and include creatine phosphate, which occurs in vertebrate skeletal muscle, heart, spermatozoa, and brain, and arginine phosphate, which occurs in invertebrate muscle. 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 a store of high-energy phosphate (Figure 8). The Role of ATP Figure 8 – : Transfer of high-energy phosphate between ATP and creatine. The Role of ATP ATP Allows the Coupling of Thermodynamically Unfavorable Reactions to Favorable Ones: The phosphorylation of glucose to glucose 6-phosphate, the first reaction of glycolysis, is highly endergonic and cannot proceed under physiologic conditions: 1. 𝐺𝑙𝑢𝑐𝑜𝑠𝑒 + 𝑃1 → 𝐺𝑙𝑢𝑐𝑜𝑠𝑒 6 − 𝑝ℎ𝑜𝑠𝑝ℎ𝑎𝑡𝑒 + 𝐻2 𝑂 (∆𝐺 𝑂 = +13.8 𝑘𝐽/𝑚𝑜𝑙) To take place, the reaction must be coupled with another—more exergonic— reaction such as the hydrolysis of the terminal phosphate of ATP. 2. 𝐴𝑇𝑃 → 𝐴𝐷𝑃 + 𝑃1 (∆𝐺 0 = −30 𝑘𝐽/𝑚𝑜𝑙) The Role of ATP ATP Allows the Coupling of Thermodynamically Unfavorable Reactions to Favorable Ones: When (1) and (2) are coupled in a reaction catalyzed by hexokinase, phosphorylation of glucose readily proceeds in a highly exergonic reaction that under physiologic conditions is irreversible. Many "activation" reactions follow this pattern. The Role of ATP Adenylyl Kinase (Myokinase) Interconverts Adenine Nucleotides: This enzyme is present in most cells. It catalyzes the following reaction: The Role of ATP Adenylyl Kinase (Myokinase) Interconverts Adenine Nucleotides: This Allows: 1. High-energy phosphate in ADP to be used in the synthesis of ATP. 2. AMP, formed as a consequence of several activating reactions involving ATP, to be recovered by rephosphorylation to ADP. 3. AMP to increase in concentration when ATP becomes depleted and act as a metabolic (allosteric) signal to increase the rate of catabolic reactions, which in turn lead to the generation of more ATP. The Role of ATP Adenylyl Kinase (Myokinase) Interconverts Adenine Nucleotides: When ATP Forms AMP, Inorganic Pyrophosphate (PPi) Is Produced ATP can also be hydrolyzed directly to AMP, with the release of PPi (Table 1). This occurs, for example, in the activation of long-chain fatty acids. The Role of ATP Adenylyl Kinase (Myokinase) Interconverts Adenine Nucleotides: This reaction is accompanied by loss of free energy as heat, which ensures that the activation reaction will go to the right and is further aided by the hydrolytic splitting of PPi, catalyzed by inorganic pyrophosphatase, a reaction that itself has a large G0' of – 19.2 kJ/mol. Note that activations via the pyrophosphate pathway result in the loss of two ~ rather than one, as occurs when ADP and Pi are formed. The Role of ATP Adenylyl Kinase (Myokinase) Interconverts Adenine Nucleotides: A combination of the above reactions makes it possible for phosphate to be recycled and the adenine nucleotides to interchange (Figure 9). Figure 9 The Role of ATP Other Nucleoside Triphosphates Participate in the Transfer of High-Energy Phosphate: By means of the enzyme nucleoside diphosphate kinase, UTP, GTP, and CTP can be synthesized from their diphosphates, eg, UDP reacts with ATP to form UTP. The Role of ATP Other Nucleoside Triphosphates Participate in the Transfer of High-Energy Phosphate: All of these triphosphates take part in phosphorylations in the cell. Similarly, specific nucleoside monophosphate kinases catalyze the formation of nucleoside diphosphates from the corresponding monophosphates. Thus, adenylyl kinase is a specialized monophosphate kinase.