4.2Role of ATP and NADH/NADPH as Energy Currencies

ATP is often referred to as the energy currency of the cell because energy obtained through its metabolism is used for biomolecule synthesis, movement, and cell division. Latest research has led to the realization that synthesis and use of ATP and other related intracellular compounds (see Chapter 6) are often associated with movement of molecules. These compounds include ATP synthase (see Chapter 16), motor proteins (see Chapter 17), and DNA/RNA polymerases (see Chapters 7 and 8). Structurally, ATP consists of the purine base adenine (see Chapter 6), pentose sugar ribose, and three phosphate groups (Fig. 4-1A). The anhydride bonds of the three phosphates make ATP a high-energy molecule. Hydrolysis of the phosphate groups at the ends of ATP produces more free energy than that of other phosphate compounds and common phosphate esters. ATP hydrolysis can be represented as follows:

ATP + H20 → ADP + inorganic phosphate
ΔG°′ = −30.5 kJ mol−1

In the description below, when mentioning ATP synthesis, it is indicated that ATP is generated by binding of an inorganic phosphate to ADP.

This free energy change generated in ATP hydrolysis is larger than that of hydrolysis of common phosphate esters. One of the reasons to explain this is probably that repulsion of the four negative charges in ATP is released in adenosine diphosphate (ADP) under neutral conditions. ATP is used in various reactions such as phosphorylation of the hydroxyl group*1 in a compound (phosphoester synthesis). In cases where a protein is the target of phosphorylation (see Chapter 14), ATP is used as a part of the signal.

Intracellular reducing power is stored in the form of coenzymes such as NADH or NADPH, which are also considered the biological energy currency (Fig. 4-1B). NADPH is generated when phosphoric acid binds to NADH. NADH and NADPH have characteristics that closely resemble redox reactions and are functionally differentiated within organisms. The two are combined here and represented as NAD(P)H. Although the oxidized form (NAD(P)) and reduced form (NAD(P)H) are both present in nature, in the following description, synthesis of the reduced form from the oxidized form is represented by NAD(P)H synthesis. NAD(P)H has considerable reducing power. Its electromotive force*2 when catalyzing a redox reaction between oxygen molecules is 1.13 V, and its standard free energy change is ΔG°′ = −218 jK mol−1 (for every two electrons). In fact, NADH synthesizes several ATP molecules in mitochondria (see Fig. 4-2). This will be described in detail in Chapter 16. The reducing power of NAD(P)H is also used to catalyze oxidation–reduction of various metabolic substances in the metabolic pathways.

*1 Also written as -OH.
*2 The oxidation potential of a substance is based on its standard redox potential that is measured using a standard hydrogen electrode (0 V). In metals, this ranking corresponds to their tendency to ionize, e.g., the standard potential of lithium (Li) is−3.04 V. In biochemistry, a pH value of 7.0 represents the neutral state, and the standard potential of hydrogen is−0.42 V, whereas in chemistry different values are used. The standard potential of oxygen is +0.82 V and that of NADH is−0.32 V. A battery is made by combining substances with different standard redox potentials (Fig. 4-2), and electromotive force is represented by the difference in the standard redox potentials of substances.

Figure 4-1 Structural formulae and reactions of ATP (A) and NAD(P)H (B)


ATP, the Basis for Taste

A lot is written about ATP at various instances in this textbook, and the role of ATP synthesis and hydrolysis is best understood as serving the function of a cogwheel, facilitating cyclic metabolism of intracellular substances. In fact, ATP is abundant in cells and occurs frequently as a biomolecule. When ATP is extracted by pulverizing rabbit muscle, it can be obtained as a clear crystal through a simple purification process. ATP is a phosphate compound, first isolated in 1929, although its function as a biological energy currency was confirmed through studies of muscles. When ATP is added to a complex of myosin and actin, two proteins extracted from muscles, contraction occurs. Muscles of living organisms contain considerable amount of ATP and expand and contract using a very complicated control mechanism. This control mechanism breaks down shortly after death, but the muscles are still capable of contraction using existing ATP. This is called rigor mortis. As time elapses, all ATP is consumed and the muscles eventually relax. Refer to Chapter 17 for further details on this mechanism of muscle contraction.

Muscular ATP is closely related to seasonings that are indispensable in daily life. Monosodium glutamate and disodium inosinate are well-known flavor enhancers. The former was discovered in kelp and the latter in dried bonito. Monosodium glutamate and disodium inosinate are currently produced by the fermentation industry. Inosic acid (IMP) is formed from ATP by removing two phosphoric acid molecules followed by the removal of the amino group at the 6′ site of ATP by deaminase. Conversely, it is also an intermediate in the pathway of ATP synthesis in organisms. In case of meat, the flavor does not develop immediately after slaughter, but only after it has been left for some time. Apart from fresh-tasting sashimi, dead fish taste delicious after some time during which the flavor is developed. During this time, ATP is converted to IMP. Bonito is a fish that has an extremely high capacity for movement and therefore contains considerable amount of ATP. During the preparation of katsuobushi, which is aided by the growth of surface mold, IMP is formed from ATP. In dashi prepared from bonito, IMP dissolves bringing out the complete flavor.

The basis of energy currency and flavors—it appears that organisms have been using ATP because it is integral to both. What a great thing ATP is—an endless mystery!

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