∆Gs of a pathway: The additive property of ∆G is very important in biochemical pathways through which substrates (reactants) must pass in a particular direction (for example, A → B → C → D → …). As long as the sum of the ∆Gs of the individual reactions is negative, the pathway can proceed as written, even if some of the individual reactions of the pathway have a positive ∆G. However, the actual rates of the reactions depend on the lowering of activation energies (Ea) by the enzymes that catalyze the reactions (see p. 55).
IV. ATP: AN ENERGY CARRIER
Reactions or processes that have a large positive ∆G, such as moving ions against a concentration gradient across a cell membrane, are made possible by coupling the endergonic movement of ions with a second, spontaneous process with a large negative ∆G such as the exergonic hydrolysis of ATP (see p. 87). [Note: In the absence of enzymes, ATP is a stable molecule because its hydrolysis has a high Ea.] Figure 6.4 shows a mechanical model of energy coupling. The simplest example of energy coupling in biologic reactions occurs when the energy-requiring and the energy-yielding reactions share a common intermediate.
A. Common intermediates
Two chemical reactions have a common intermediate when they occur sequentially in that the product of the first reaction is a substrate for the second. For example, given the reactions
D is the common intermediate and can serve as a carrier of chemical energy between the two reactions. [Note: The intermediate may be linked to an enzyme.] Many coupled reactions use ATP to generate a common intermediate. These reactions may involve the transfer of a phosphate group from ATP to another molecule. Other reactions involve the transfer of phosphate from an energy-rich intermediate to adenosine diphosphate (ADP), forming ATP.
B. Energy carried by ATP
ATP consists of a molecule of adenosine (adenine + ribose) to which three phosphate groups are attached (Fig. 6.5). Removal of one phosphate produces ADP, and removal of two phosphates produces adenosine monophosphate (AMP). For ATP, the ∆G0 of hydrolysis is approximately – 7.3 kcal/mol for each of the two terminal phosphate groups. Because of this large negative ∆G0 of hydrolysis, ATP is called a high-energy phosphate compound. [Note: Adenine nucleotides are interconverted (2 ADP ⇄ ATP + AMP) by adenylate kinase.]
V. ELECTRON TRANSPORT CHAIN
Energy-rich molecules, such as glucose, are metabolized by a series of oxidation reactions ultimately yielding carbon dioxide and water (H2O), as shown in Figure 6.6. The metabolic intermediates of these reactions donate electrons to specific coenzymes, nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD), to form the energy-rich reduced forms, NADH and FADH2. These reduced coenzymes can, in turn, each donate a pair of electrons to a specialized set of electron carriers, collectively called the electron transport chain (ETC), described in this section. As electrons are passed down the ETC, they lose much of their free energy. This energy is used to move H+ across the inner mitochondrial membrane, creating a H+ gradient that drives the production of ATP from ADP and inorganic phosphate (Pi), described on p. 77. The coupling of electron transport with ATP synthesis is called oxidative phosphorylation, sometimes denoted as OXPHOS. It proceeds continuously in all tissues that contain mitochondria. [Note: The free energy not trapped as ATP is used to drive ancillary reactions such as transport of calcium ions into mitochondria and to generate heat.]
A. Mitochondrial electron transport chain