Biochemistry and Molecular Biology - Belyasova N.A. 2002

Structure and Functions of Cellular Components
Cofactors
Phosphate Group Carriers. Energy Transduction in the Cell

Cofactors that serve as phosphate group carriers are essential components of at least 225 Enzymes. The vast majority of these enzymes are specific to adenosine diphosphate (ADP) and are referred to as Kinases. A typical kinase reaction can be represented schematically as follows:

Class="center">x-P_i + ADP → x + ATP,      (7.1)

where x-P_i is a phosphorylated substrate acting as a donor of inorganic phosphate (P_i); ADP is the phosphate group acceptor; x is the dephosphorylated donor; and ATP is adenosine triphosphate.

This reaction may be followed by another kinase reaction (Equation 7.2) or a synthetase reaction (Equation 7.3):

y + ATP → y-P_i + ADP      (7.2)

y + z + ATP → y-z + ADP + P_i      (7.3)

It is easy to see that reactions of types 7.2 and 7.3 release ADP, which can then participate once again in a type 7.1 reaction, providing the rationale for classifying adenosine diphosphate as a cofactor.

In type 7.1 reactions, ATP is formed—an energy-rich molecule that serves as the primary energy supplier in cellular processes. In type 7.2 reactions, ATP acts as a phosphate group donor, while in type 7.3 reactions, it acts as an energy donor for the interaction between substance "y" and substance "z". Essentially, however, ATP Functions as a coupling agent that enables reactions 7.2 and 7.3 to proceed at the expense of The breakdown of substance x-P_i (reaction 7.1).

Structural Features of the ATP molecule. Adenosine triphosphate has a unique Structure (Fig. 7.6): at pH values close to 7, the triphosphate moiety carries approximately four negative charges that are in close proximity to one another and experience strong mutual repulsion. Electrostatic repulsion between the charged groups is alleviated upon ATP Hydrolysis. Furthermore, ATP is characterized by lower Resonance stabilization than the products of its hydrolysis, ADP and P_i. Thus, ATP is a thermodynamically unstable molecule and undergoes hydrolysis to yield ADP or AMP. In the process, high-energy bonds (denoted by the symbol ~) are cleaved, and a large amount of energy is released.

During the hydrolysis of ATP high-energy bonds at pH 7 under standard conditions, The change in Free energy ranges from -30 to -35 kJ/mol, regardless of which of the ATP anhydride bonds is cleaved. This energy can be utilized to drive endergonic reactions or to activate molecules (certain substances can undergo transformations only in their activated form). Consequently, a thermodynamically unfavorable reaction can be rendered thermodynamically favorable by coupling it with ATP hydrolysis.

The active form of ATP is a complex with a Mg²⁺ ion coordinated to the α- and β-phosphates.

Fig. 7.6. STRUCTURE OF THE ATP molecule

Strictly speaking, ATP is a directly utilized donor of free energy rather than a storage form: an ATP molecule is typically consumed within 1 minute of its formation. It is known that a resting human consumes up to 40 kg of ATP per 24 hours, and during intense physical exertion, The rate of ATP utilization can reach 0.5 kg/min. Vital processes such as movement, active Transport of substances across membranes, Biosynthesis, maintenance of body Temperature, osmoregulation, Generation and Conduction of nerve impulses, Bioluminescence, and Muscle contraction all require continuous ATP regeneration. How is ATP generated?

ATP formation. Adenosine triphosphate—the "primary energy currency of The Cell"—can be generated through several processes involving the following mechanisms.

1. Oxidative Phosphorylation, which takes place during Respiration (aerobic or anaerobic) and requires the obligatory involvement of membranes. The driving force for ATP synthesis is the energy of the proton gradient across the membrane.

2. Photophosphorylation, a mechanism of transforming light energy into the energy of high-energy ATP bonds during Photosynthesis. This process also requires the participation of Introduction/36.html">Biological Membranes, as the driving force for ATP synthesis is likewise the energy of the proton gradient across the membrane.

3. Substrate-level phosphorylation. In this case, ATP is synthesized during the breakdown of high-energy bonds in certain metabolites. The process does not require membranes and occurs in Catabolic pathways as well as during certain Types of Fermentation.

In all of the aforementioned processes, ATP is formed from ADP and inorganic phosphate. In turn, ADP can be generated from ATP and AMP through interconversions catalyzed by the enzyme adenylate kinase in accordance with the following reaction equation:

АТР + АМР ↔ АDP + АDP      (7.4)

It is important to note that in terms of its Phosphate group transfer potential, ATP occupies an intermediate position among biologically important phosphorylated molecules, functioning as both an energy donor and acceptor in METABOLISM. This implies that there must exist compounds characterized by a higher inorganic phosphate transfer potential than ATP. These compounds (acetyl phosphate, creatine phosphate, phosphoenolpyruvate, 1,3-bisphosphoglycerate, carbamoyl phosphate, and several others) also contain high-energy bonds and are referred to as high-energy compounds.

The principal hallmark of a high-energy bond is that its Cleavage or formation is accompanied by A change in Free energy of a much greater magnitude (averaging 25–50 kJ/mol) than that associated with the Transformation of a standard bond (on the order of 12.5 kJ/mol). High-energy bonds are represented mainly by ester bonds (including thioester bonds), anhydride bonds (as found in the ATP molecule), and phosphoamide bonds. Practically all known high-energy compounds contain sulfur and phosphorus atoms at the sites where these bonds are localized. Adenosine diphosphate, acting as a kinase cofactor, serves as a mobile phosphate group carrier and can be classified as a coenzyme.

Certain enzymes utilize other nucleoside diphosphates—such as GDP, UDP, or CDP—as phosphate group carriers, although such reactions are relatively uncommon.