ADP captures, in the form of high-energy phosphate, a significant proportion of the free energy released by catabolic processes. The resulting ATP has been called the energy “currency” of the cell because it passes on this free energy to drive those processes requiring energy.
There is a net direct capture of two high-energy phosphate groups in the glycolytic reactions . Two more high-energy phosphates per mole of glucose are captured in the citric acid cycle during the conversion of succinyl-CoA to succinate. All of these phosphorylations occur at the substrate level. For each mol of substrate oxidized via Complexes I, III, and IV in the respiratory chain (ie, via NADH), 2.5 mol of ATP are formed per 0.5 mol of O2 consumed, that is, the P:O ratio = 2.5 (see Figure 1). On the other hand, when 1 mol of substrate (eg, succinate or 3-phophoglycerate) is oxidized via Complexes II, III, and IV, only 1.5 mol of ATP are formed, that is, P:O = 1.5. These reactions are known as oxidative phosphorylation at the respiratory chain level. Taking these values into account, it can be estimated that nearly 90% of the high-energy phosphates produced from the complete oxidation of 1 mol glucose is obtained via oxidative phosphorylation coupled to the respiratory chain .
Fig1. The chemiosmotic theory of oxidative phosphorylation. Complexes I, III, and IV act as proton pumps creating a proton gradient across the membrane, which is negative on the matrix side. The proton motive force generated drives the synthesis of ATP as the pro tons flow back into the matrix through the ATP synthase enzyme (Figure 2). Uncouplers increase the permeability of the membrane to ions, collapsing the proton gradient by allowing the H+ to pass across without going through the ATP synthase, and thus uncouple electron flow through the respiratory complexes from ATP synthesis. (cyt, cytochrome; Q, coenzyme Q or ubiquinone.)
Respiratory Control Ensures a Constant Supply of ATP
The rate of respiration of mitochondria can be controlled by the availability of ADP. This is because oxidation and phosphorylation are tightly coupled; that is, oxidation cannot proceed via the respiratory chain without concomitant phosphorylation of ADP. Table 1 shows the five conditions controlling the rate of respiration in mitochondria. Most cells in the resting state are in state 4, and respiration is controlled by the availability of ADP. When work is performed, ATP is converted to ADP, allowing more respiration to occur, which in turn replenishes the store of ATP. Under certain conditions, the concentration of inorganic phosphate can also affect the rate of functioning of the respiratory chain. As respiration increases (as in exercise), the cell approaches states 3 or 5 when either the capacity of the respiratory chain becomes saturated or the PO2 decreases below the Km for heme a3 . There is also the possibility that the ADP/ATP transporter, which facilitates entry of cytosolic ADP into and ATP out of the mitochondrion, becomes rate limiting.
Table1. States of Respiratory Control
Thus, the manner in which biologic oxidative processes allow the free energy resulting from the oxidation of food stuffs to become available and to be captured is stepwise, efficient, and controlled—rather than explosive, inefficient, and uncontrolled, as in many nonbiologic processes. The remaining free energy that is not captured as high-energy phosphate is liberated as heat. This need not be considered “wasted” since it ensures that the respiratory system as a whole is sufficiently exergonic to be removed from equilibrium, allowing continuous unidirectional flow and constant pro vision of ATP. It also contributes to maintenance of body temperature.
