BIOCHEMISTRY - L. Stryer - 1984

VOLUME 2

PART II GENERATION AND STORAGE OF METABOLIC ENERGY

CHAPTER 14. OXIDATIVE PHOSPHORYLATION

14.12. Complete Oxidation of Glucose Yields 36 ATP

We can now calculate The amount of ATP formed during the complete oxidation of glucose (Table 14.4). The overall reaction is:

Glucose + 36ADP + 36Pi + 36Н⁺ + 6O₂ → 6СO₂ + 36АТР + 42Н₂O.

Class="center">Table 14.4. ATP Yield from the Complete Oxidation of Glucose

The P:O ratio is 3, since 36 ATP molecules are formed while 12 oxygen atoms are consumed. The majority of the ATP—32 out of 36 molecules—is generated via Oxidative Phosphorylation.

The overall efficiency of ATP generation reaches a high level. The oxidation of glucose under standard conditions releases 686 kcal:

Glucose + 6O₂ → 6СO₂ + 6Н₂O

∆G⁰' = - 686 kcal.

The Free energy stored in 36 ATP molecules amounts to 263 kcal, given that ∆G⁰' for ATP Hydrolysis is –7.3 kcal. Hence, the thermodynamic efficiency of ATP formation from glucose under standard conditions reaches 263/686, or 38%.

The respiratory quotient (RQ), a frequently used indicator in whole-Organism METABOLISM studies, is defined as follows:

For the complete oxidation of CARBOHYDRATES, the RQ is 1. For fats and Proteins, it is 0.71 and 0.80, respectively. Thus, the RQ can serve as an indicator of the relative utilization of carbohydrates, fats, and proteins by the organism.

14.13. The Rate of Oxidative Phosphorylation is Determined by ATP Demand

Under most physiological conditions, Electron transport is tightly coupled to phosphorylation. Electrons are typically transferred along the Electron Transport Chain only when accompanied by the simultaneous phosphorylation of ADP to ATP. Oxidative phosphorylation requires a supply of NADH (or another high-potential electron source), O₂, ADP, and Pi. The most critical factor in determining The rate of Oxidative phosphorylation is the ADP concentration. Upon The addition of ADP, the rate of oxygen consumption by a tissue homogenate increases significantly and then returns to baseline once all the added ADP has been converted into ATP (Fig. 14.12).

Fig. 14.12. Respiratory Control. Electrons are transferred to O₂ only when ADP is phosphorylated to ATP

The Regulation of the rate of oxidative phosphorylation by ADP levels is known as respiratory control. The physiological significance of this regulatory mechanism is obvious. ADP levels rise when ATP is consumed, thereby tightly coupling oxidative phosphorylation to ATP utilization. In the absence of a demand for ATP synthesis, no Electron transfer from fuel molecules to O₂ takes place.

14.14. Dinitrophenol Uncouples Oxidative Phosphorylation by Disrupting the Proton Gradient

The tight coupling between Electron Transport and phosphorylation is disrupted by 2,4-dinitrophenol (DNP) and certain other acidic Aromatic Compounds (Fig. 14.13). These compounds shuttle protons across The inner mitochondrial membrane. Electron transfer from NADH to O₂ proceeds normally in the presence of such uncouplers, but ATP formation by mitochondrial ATPase fails to occur because the proton-motive force driving protons across the inner mitochondrial membrane is abolished. The loss of respiratory control leads to an increase in both O₂ consumption and NADH oxidation. At the same time, DNP has no effect on substrate-level phosphorylation. Due to their specific action on the Respiratory Chain, DNP and other uncouplers serve as valuable tools in metabolic research.

Fig. 14.13. Chemical structures of two uncouplers of oxidative phosphorylation. These lipid-soluble compounds can transport protons across the inner mitochondrial membrane. The dissociable proton is highlighted in red

The uncoupling of oxidative phosphorylation can be biologically beneficial. It serves as a mechanism for generating heat to maintain body Temperature in hibernating animals, certain newborn mammals, and cold-adapted mammals. Brown adipose tissue, which is exceptionally rich in Cell/35.html">Mitochondria, is specialized for this thermogenic process. Fatty acids act as uncouplers in this tissue, with their release regulated by norepinephrine. Consequently, the degree of oxidative phosphorylation uncoupling in brown Adipose tissue is under hormonal control. The mitochondria in this tissue can function either as ATP generators or as miniature heating units.

An interesting case has been reported of a 38-year-old woman who was unable to perform sustained physical work. Her basal metabolic rate was more than twice the normal level, yet her thyroid function was completely normal. Muscle biopsy revealed that her mitochondria were highly pleomorphic and structurally atypical. Biochemical analysis demonstrated that these mitochondria were not subject to respiratory control; they oxidized NADH independently of the presence of ADP. In other words, there was a loss of tight coupling between oxidation and phosphorylation. The P : O ratio was lower than normal. Thus, in this patient, a significant portion of the energy derived from fuel molecules was dissipated as heat rather than being captured as ATP. The Nature of the molecular defect in such mitochondria remains to be elucidated.