Biochemistry and Molecular Biology - Belyasova, N. A. 2002

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

Cofactors that act 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 can 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 reactions of type 7.1, thus providing grounds for classifying adenosine diphosphate as a cofactor.

In a type 7.1 reaction, ATP is formed—an energy-rich substance and the primary supplier of energy in cellular processes. In a type 7.2 reaction, ATP acts as a phosphate group donor, whereas in a type 7.3 reaction, it serves 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 about four negative charges that are located in close proximity to one another and experience strong mutual repulsion. Electrostatic repulsion between the charged groups is diminished upon ATP Hydrolysis. Furthermore, ATP exhibits lower Resonance stabilization than its hydrolysis products, ADP and P_i. Consequently, ATP is a thermodynamically unstable molecule and undergoes hydrolysis to yield ADP or AMP. This process involves the Cleavage of high-energy bonds (denoted by the symbol ~) and the release of a large amount of energy.

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 requiring an energy input or to activate molecules (certain substances can undergo transformations only in an activated state). As a result, 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 serves as a directly utilized donor of free energy rather than a form of energy storage: an ATP molecule is typically consumed within 1 minute of its formation. It is known that a resting human expends up to 40 kg of ATP over 24 hours, and during intense physical activity, The rate of ATP utilization can reach 0.5 kg/min. Such vital processes as locomotion, active Transport of substances across membranes, Biosynthesis, maintenance of body Temperature, osmoregulation, Generation and Conduction of nerve impulses, Bioluminescence, and Muscle contraction require continuous ATP regeneration. How is ATP generated?

ATP generation. Adenosine triphosphate—the "cellular energy currency"—can be produced through several processes involving the following mechanisms.

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

2. Photophosphorylation, a mechanism for converting light energy into the energy of ATP high-energy bonds, which occurs during Photosynthesis. This process also requires the involvement of Introduction/36.html">Biological Membranes, since the driving force for ATP synthesis here 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 membrane participation and takes place in Catabolic pathways and during certain Types of Fermentation.

In all these processes, ATP is formed from ADP and inorganic phosphate. In turn, ADP can be produced from ATP and AMP via 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 (such as acetyl phosphate, creatine phosphate, phosphoenolpyruvate, 1,3-diphosphoglycerate, carbamoyl phosphate, and several others) also contain high-energy bonds and are referred to as high-energy compounds.

The primary characteristic of a high-energy bond is that its cleavage or formation is accompanied by a much larger change in free energy (on average 25–50 kJ/mol) than the Transformation of a standard bond (around 12.5 kJ/mol). High-energy bonds are predominantly ester bonds, including thioester bonds, anhydride bonds (as in the ATP molecule), and phosphoamide bonds. Virtually all known high-energy compounds contain sulfur and phosphorus atoms at the sites where these bonds are localized. Adenosine diphosphate, acting as a cofactor for kinases, 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, though such reactions are relatively uncommon.