BIOCHEMISTRY - L. Stryer - 1984

VOLUME 2

PART II GENERATION AND STORAGE OF METABOLIC ENERGY

CHAPTER 11 METABOLISM: BASIC CONCEPTS AND DESIGN

11.4. ATP Is the Universal Energy Currency of Biological Systems

Living organisms require a continuous input of Free energy to perform three major kinds of work: 1) mechanical work in Muscle contraction and other cellular movements, 2) active Transport of Molecules and ions, and 3) the synthesis of macromolecules and other Biomolecules from simple precursors. The free energy used in these processes, which maintains living systems far from equilibrium, comes from the environment. Chemotrophs obtain this energy by oxidizing foodstuffs, whereas phototrophs capture it from light. The free energy released in nutrient oxidation or captured from light is partially converted into a special form before being utilized in movement, Active Transport, and Biosynthesis. This specialized free-energy carrier, a cellular energy currency of sorts, is adenosine triphosphate (ATP). The Central Role of ATP in biological energy exchange was elucidated by Fritz Lipmann and Herman Kalkar in 1941.

ATP is a nucleotide consisting of adenine, ribose, and a triphosphate unit (Fig. 11.2; for a Structure/133.html">Discussion of nucleotide nomenclature, see Section 22.1). The active form of ATP is usually a complex of ATP with Mg^{2 +} or Мn²⁺. In considering The Role of ATP as an energy carrier, we focus primarily on its triphosphate moiety. ATP is an energy-rich molecule because its triphosphate unit contains two phosphoanhydride bonds. The Hydrolysis of ATP to adenosine diphosphate (ADP) and orthophosphate (Pi), or to adenosine monophosphate (AMP) and pyrophosphate (PPi), is accompanied by the release of a large amount of free energy. ∆G⁰ for these reactions depends on the Ionic strength of the medium and the concentrations of Mg²⁺ and Са²⁺. We will use the value of -7.3 kcal/mol. Under normal intracellular conditions, the actual value of ∆G for these hydrolysis processes is approximately -12 kcal/mol.

Class="center">Fig. 11.2. Adenosine triphosphate consists of an adenine unit (blue), a ribose unit (yellow), and a triphosphate unit (red)

АТР + Н₂O ⇄ ADP + Рi + Н⁺

∆G⁰ = - 7,3 kcal/mol,

АТР + H₂O ⇄ АМР + РРi + Н⁺

∆G⁰ = - 7,3 kcal/mol.

ATP, AMP, and ADP are interconvertible. The enzyme adenylate kinase (also called myokinase) catalyzes the reaction

АТР + AMP ⇄ ADP + ADP.

Fig. 11.3. Structures of ATP, ADP, and AMP. (Adenosine consists of adenine linked to ribose.)

The free energy released in the hydrolytic Cleavage of the anhydride bond of ATP is used to drive reactions that require an input of free energy, such as muscle contraction. ATP, in turn, is formed from ADP and Pi during The oxidation of fuel molecules in chemotrophs or the Utilization of Light in phototrophs. This ATP-ADP cycle represents the fundamental mechanism of energy exchange in biological systems.

Certain biosynthetic reactions are driven by NUCLEOTIDES analogous to ATP, namely guanosine triphosphate (GTP), uridine triphosphate (UTP), and cytidine triphosphate (CTP). The diphosphate forms of these nucleotides are designated as GDP, UDP, and CDP, respectively. Enzymes catalyze The transfer of a terminal phosphoryl group from one nucleotide to another:

АТР + GDP ⇄ ADP + GTP,

АТР + GMP ⇄ ADP + GDP.

11.5. ATP Is Continuously Formed and Consumed

ATP serves as the primary immediate donor of free energy in biological systems rather than as a long-term energy storage form. In a typical Cell, an ATP molecule is consumed within one minute of its formation. The turnover rate of ATP is extremely high. For example, a resting human uses about 40 kg of ATP over 24 hours. During intense exercise, The rate of ATP utilization can reach 0.5 kg/min. Movement, active transport, signal Amplification, and biosynthetic processes can proceed only if ATP is continuously regenerated from ADP (Fig. 11.4). Phototrophs derive free energy from sunlight to generate ATP from ADP, whereas chemotrophs generate ATP through the oxidation of fuel molecules.

Fig. 11.4. The ATP-ADP cycle is the fundamental mechanism of energy exchange in biological systems

11.6. Structural Basis of ATP, Determining Its High Group-Transfer Potential

Let us compare the Standard Free Energy of ATP hydrolysis with that of a typical phosphate ester such as glycerol 3-phosphate:

АТР + Н₂О ⇄ ADP + Рi + Н⁺

∆G⁰' = — 7,3 kcal/mol,

Glycerol 3-phosphate + Н₂O ⇄ Glycerol + Рi

∆G⁰' = - 2,2 kcal/mol.

The value of ∆G⁰ for the hydrolysis of glycerol 3-phosphate is significantly lower than that for ATP hydrolysis. This means that ATP has a much stronger tendency to transfer its terminal phosphoryl group to a Water molecule than does glycerol 3-phosphate. In other words, ATP possesses a higher phosphate-group transfer potential than glycerol 3-phosphate.

What is the structural basis for the high phosphate-group transfer potential inherent in ATP? To answer this question, we must analyze the structures of ATP and its hydrolysis products, ADP and Pi, because ∆G⁰ depends on the difference in free energy between the reaction products and the reactant compounds. Two factors have been proven to play an important role in this aspect: electrostatic repulsion and Resonance stabilization. At pH 7, the triphosphate moiety of ATP carries about four negative charges. These charges strongly repel one another because they are in close proximity. Electrostatic repulsion among these negatively charged groups is alleviated upon the hydrolysis of ATP. Another factor contributing to the high group-transfer potential of ATP is the greater resonance stabilization of ADP and Pi compared with that of ATP. For example, orthophosphate has a certain number of resonance structures of equal energy (Fig. 11.5). In contrast, the terminal portion of ATP has fewer significant resonance forms per phosphate group. Resonance forms of the type shown in Fig. 11.6 are unlikely to exist, because in this case two phosphorus atoms would compete for the electron pairs on oxygen. Furthermore, placing a positive charge on oxygen in close proximity to a positively charged phosphorus atom is electrostatically unfavorable.

Fig. 11.5. Significant resonance forms of orthophosphate

Fig. 11.6. Unlikely resonance form of the terminal part of ATP

Various Other Compounds in biological systems exhibit a high phosphate-group transfer potential. Some of them, such as phosphoenolpyruvate, acetyl phosphate, and creatine phosphate (Fig. 11.7), have an even higher group-transfer potential than ATP. This means that phosphoenolpyruvate can transfer its phosphoryl group to ADP to yield ATP. Indeed, this is one of the pathways for ATP synthesis during carbohydrate breakdown. Importantly, in terms of its phosphate-group transfer potential, ATP occupies an intermediate position among biologically important phosphorylated molecules (Table 11.2). Because of this intermediate status, ATP Functions efficiently as a carrier of phosphoryl groups.

Table 11.2. Free energy of hydrolysis for various phosphorylated compounds

ATP is frequently referred to as a high-energy phosphate compound, and its phosphoanhydride bonds are often called high-energy bonds. It should be noted that these bonds do not possess any special properties in themselves. They are termed "high-energy" in the sense that their hydrolysis releases a large amount of free energy (for the reasons outlined above). The term "high-energy bond," introduced by Lipmann, along with his proposed symbol ~ P to designate compounds with a high phosphate-group transfer potential, provides a vivid, concise, and convenient notation. Lipmann's concepts played a major role in stimulating interest in Bioenergetics.

Fig. 11.7. Compounds with a higher phosphate-group transfer potential than ATP