ATP as cellular energy currency readings PDF

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ATP as cellular energy currency readingsATP as cellular energy currency readingsATP as cellular energy currency readingsATP as cellular energy currency readings...

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ATP as cellular energy currency The cell needs to make, store, and use energy, just as an individual needs to make, store, and use money. Without money, a person cannot acquire goods and services. Without energy, a cell cannot synthesize metabolites or carry out physiological functions. What molecule should we use as our “energy currency”? All cells rely primarily on the formation and hydrolysis of phosphorylated chemicals, especially ATP. The nucleotide triphosphate ATP is the cell’s most important reservoir of free energy available for immediate use. Fritz Lipmann first recognized the significance of ATP and other phosphorylated compounds in bioenergetics. (He also discovered the cofactor Coenzyme A)

ATP is a nucleotide, comprising a base (adenine), a sugar (ribose), and three phosphate groups, which we label alpha, beta, and gamma. A 70kg person uses about 40kg of ATP during a restful day!! (assuming an ~50% efficiency of converting food energy (8400 kJ/2000 kcal/per day) into ATP) ATP is not a store of chemical energy; rather it’s a link between catabolism and anabolism ATPs role in the cell is analogous to that of money in an economy: it is “earned/produced” in exergonic reactions and “spent/consumed” in endergonic ones. Cells breakdown nutrient molecules (catabolism) and use the available free energy to synthesize ATP from ADP. ATP then donates its energy to endergonic processes that require energy (synthesis of metabolic intermediates and macromolecules (anabolism), active transport across membranes, mechanical motion etc.). ATP turns over (broken down and synthesized) very rapidly in cells; the typical lifetime of an ATP molecule is measured in seconds to minutes. The free energy change for hydrolysis of ATP is large and negative Why did we choose ATP as our energy currency? Most hydrolysis reactions are energetically favourable, but the ΔG value (free energy released by hydrolysis) depends on the nature of the bond being hydrolyzed. Typical values for amides, esters, and phosphoesters are about 15-20 kJ per mol. We want to use the hydrolysis of our currency to drive common reactions forward – i.e., Synthesis of proteins, starches and other molecules. This means that we need a more “valuable” currency, i.e., a chemical for which ΔGhydrolysis is considerably higher than 20 kJ per mol. The ΔGhydrolysis for ATP is about 50 kJ/mol. It is at the phosphates that the energy-requiring/ releasing processes take place. Being energy rich however, is not the only reason for choosing ATP as the energy currency. The fact that ATP is metabolically available (it’s a RNA building block), kinetically stable (does not undergo hydrolysis unless catalyzed by an enzyme) and chemically versatile (can take part in reactions through many different mechanisms; group transfer reactions) also were reasons for ATP being chosen as the universal energy currency. Page 1 of 4

ATP as cellular energy currency Chemical basis for the large free-energy change associated with ATP hydrolysis Why does hydrolysis of a phosphoanhydride have such a high ΔG value? 1. The components of the phosphoanhydride are very negatively charged; hydrolysis releases this electrostatic repulsion among these charges, as the negatively charged products fly apart. 2. The product inorganic phosphate has greater resonance stabilization than does ATP. 3. The ADP product of hydrolysis rapidly loses another proton (ionizes); by Le Chatelier’s principle, that drives the hydrolysis towards completion. These aspects of ATP chemistry are discussed in N&C - see Fig. 13-11. High-energy bonds: People often refer to the beta and gamma phosphoanhydride linkages of ATP as “high-energy bonds”, and even to draw them as “squiggles”: A—PPP. This shorthand notation is useful, because it reminds us that hydrolysis of the beta and gamma phosphoanhydride bonds releases a lot more energy than hydrolysis of the alpha phosphate, which is just a phosphate ester. But do not be misled into thinking that the phosphoanhydride bonds themselves are unusual (short? long? squiggly?). The energy is not associated with the bond, but with the overall hydrolysis reaction; it is a property of the ATP molecule, not a property of the bond itself. Hydrolysis of ATP There are two “high-energy bonds” (phosphoanhydride linkages) in ATP, the beta and gamma phosphoanhydride linkages. Either could be hydrolyzed, and, indeed, some enzymes catalyze one mode of hydrolysis and some the other. 1. Hydrolysis of the link between gamma and beta phosphate (nucleophilic attack of the gamma phosphate) yields ADP and Pi, as already discussed.

2. Hydrolysis of the alpha-beta linkage nucleophilic attack of the alpha phosphate) yields AMP and pyrophosphate (PPi). This compound is a dimer of phosphoric acid moieties linked by a phosphoanhydride bond, and it is still a “high-energy” compound.

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PPi

ATP as cellular energy currency ATP

AMP + PPi

In the cell, pyrophosphate usually undergoes further hydrolysis to give two moles of P i, in a reaction catalyzed by the enzyme pyrophosphatase. PPi

2 Pi

Pyrophosphatase

Net: ATP

AMP + 2 Pi

So, the hydrolysis of ATP to AMP and PP i is tantamount to the complete hydrolysis of ATP to AMP + 2 Pi, which is to say, the hydrolysis of both of the high-energy bonds in ATP. In effect, the free energy of hydrolysis of ATP to AMP + PP i is twice as large as the free energy of hydrolysis of ATP to ADP + Pi. How does hydrolysis of ATP drive energetically-unfavourable reactions? This is a very important concept. You are going to see, many times, the notation shown on the left, indicating that a reaction (say, a biosynthesis, or a transport process, or some other energy-requiring step) is “driven by the hydrolysis of ATP”. In a thermodynamic sense, this means that the free energy needed to drive the reaction forward (overcoming its positive free energy change) is supplied by ATP hydrolysis. This is true; it is equivalent to saying that the electrical energy supplied through the mains provides the energy needed to turn the blades of a food processor; or, that the chemical energy in gasoline provides the energy needed to drive a car forward. It is a valid thermodynamic statement but it tells us nothing about mechanism. So, whenever you see that “driven by the hydrolysis of ATP” arrow notation, you must ask yourself, “What is the chemical mechanism that allows ATP hydrolysis to drive this reaction forward?” How ATP drives an energy-requiring reaction: an example Glutamine synthetase provides a nice example of the use of ATP energy in biochemistry. Glutamine is one of the twenty amino acid building blocks of proteins. It is chemically similar to glutamate, another of the building blocks. In fact, glutamine is synthesized from glutamate, by the enzyme-catalyzed condensation of ammonia with the gamma-carboxylic acid moiety of glutamate. This condensation gives the corresponding amide: glutamine (top reaction). This reaction is energetically “uphill”; the reverse reaction, hydrolysis of glutamine to glutamate and ammonia, is spontaneous. The cell drives the synthesis of glutamine forward by coupling the reaction to ATP hydrolysis, as illustrated by the ATP  ADP + Pi notation. The mechanism of the enzyme-catalyzed reaction, in which the synthetic reaction is coupled to ATP hydrolysis, is known in Page 3 of 4

ATP as cellular energy currency considerable detail. The reaction occurs in two steps. ATP is a reactant, even though it does not appear in the stoichiometry “glutamate + ammonia  glutamine”. In the first step, ATP reacts with glutamate to produce a covalent intermediate, a mixed anhydride of phosphate and glutamate. In the second step, ammonia, acting as a nucleophile, reacts with the electrophilic carbonyl carbon atom. Pi, the leaving group, is displaced. We have already discussed some of the reasons why ATP is a suitable energy currency for the cell. Now we see another important aspect of ATP biochemistry. Phosphorylated compounds such as ATP are chemically versatile: the phosphate group can participate in a variety of chemical reactions with common organic functional groups. Our currency is accepted wherever we wish to spend it. In addition to the phosphoryl group, ATP can also transfer a pyrophosphoryl (PPi) or an adenylate (AMP) moiety to a substrate or to an amino acid residue of an enzyme helping to drive reactions forward. Therefore, it is obvious that ATP provides energy not by simple hydrolysis but through group transfer. We have said that hydrolyses of phosphoanhydrides have high negative ΔG values. Here is a chart (it’s a simplified version of Fig. 13-19 in N&C) showing the relative ΔG values for hydrolysis of some biochemically-important phosphorylated molecules and for acetyl CoA. (The ΔG scale is flipped, with negative values at the top, so that the “highest-energy” compounds are at the top of the hill.) At the bottom - zero - is inorganic phosphate, which can’t be hydrolyzed at all; it’s the product of hydrolysis. Simple phosphate esters of alcohols, like sugar phosphates are “lowenergy” phosphate bonds; hydrolysis of these compounds is energetically comparable to hydrolysis of simple esters or amides. ATP, as we have said, is a “high-energy” phosphate compound. Above ATP are some “super-high-energy” phosphate compounds, like phosphoenol-pyruvate and creatine phosphate. Creatine phosphate stores energy in muscles. “Super-highenergy” phosphate compounds can generate ATP directly, by the energetically-favourable transfer of the phosphate group to ADP.

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