In an automobile engine, hydrocarbon fuel is oxidatively and explosively converted in an essentially one-step process to mechanical work (i.e., driving a piston) plus the products CO2 and H2O. The process is relatively inefficient in that substantial amounts of the chemical energy stored in the fuel are wasted, as they are converted to unused heat, and substantial amounts of fuel are only partially oxidized and are released as carbonaceous, sometimes toxic, exhaust. In the competition to survive, organisms cannot afford to squander their sometimes limited energy sources on an equivalently inefficient process and have therefore evolved a more efficient mechanism for converting fuel into work. That mechanism, known as aerobic oxidation, pro vides the following advantages:
● By dividing the energy conversion process into multiple steps that generate several energy-carrying intermediates, chemical bond energy is efficiently channeled into the synthesis of ATP, with little energy lost as heat
● Different fuels (sugars and fatty acids) are reduced to common intermediates that can then share subsequent pathways for combustion and ATP synthesis.
● Because the total energy stored in the bonds of the initial fuel molecules is substantially greater than that required to drive the synthesis of a single ATP molecule (~7.3 kcal/mol), many ATP molecules are produced.
An important feature of ATP production from the breakdown of nutrient fuels into CO2 and H2O (see Figure 1, top) is a set of reactions, called respiration, in volving a series of oxidation and reduction reactions called an electron-transport chain. The combination of these re actions with phosphorylation of ADP to form ATP is called oxidative phosphorylation and occurs in mitochondria in nearly all eukaryotic cells. When oxygen is available and is used as the final recipient of the electrons transported via the electron-transport chain, the respiratory process that converts nutrient energy into ATP is called aerobic oxidation or aerobic respiration. Aerobic oxidation is an especially efficient way to maximize the conversion of nutrient energy into ATP because O2 is a relatively strong oxidant. If some molecule other than O2—for example, the weaker oxidants sulfate (SO42−) or nitrate (NO3−)—is the final recipient of the electrons in the electron-transport chain, the process is called anaerobic respiration. Anaerobic respiration is typical of some prokaryotic microorganisms. Although there are exceptions, most known multicellular (metazoan) eukaryotic organisms use aerobic oxidation to generate most of their ATP.
Fig1. Overview of aerobic oxidation and photosynthesis. Eukaryotic cells use two fundamental mechanisms to convert external sources of energy into ATP. (Top) In aerobic oxidation, “fuel” molecules [primarily sugars and fatty acids (lipids)] undergo preliminary processing in the cytosol, such as breakdown of glucose to pyruvate (stage I), and are then transferred into mitochondria, where they are converted by oxidation with O2 to CO2 and H2O (stages II and III) and ATP is generated (stage IV). (Bottom) In photosynthesis, which occurs in chloroplasts, the radiant energy of light is absorbed by specialized pigments (stage 1); the absorbed energy is used both to oxidize H2O to O2 and to establish conditions (stage 2) necessary for the generation of ATP (stage 3) and of carbohydrates from CO2 (carbon fixation, stage 4). Both mechanisms involve the production of reduced high-energy electron carriers (NADH, NADPH, FADH2) and the movement of electrons down an electric potential gradient in an electron-transport chain through specialized membranes. Energy released from these electrons is captured as a pro ton electrochemical gradient (proton-motive force) that is then used to drive ATP synthesis. Bacteria use comparable processes.
In our discussion of aerobic oxidation, we will be tracing the fate of the two main cellular fuels: sugars (principally glucose) and fatty acids. Under certain conditions—for example, starvation conditions—amino acids also feed into these metabolic pathways. We first consider glucose oxidation, then turn to fatty acids.
The complete aerobic oxidation of one molecule of glucose yields 6 molecules of CO2, and the energy released is coupled to the synthesis of as many as 30 molecules of ATP. The overall reaction is
C6H12O6 + 6 O2 + 30 Pi2− + 30 ADP3− + 30 H+ → 6 CO2 + 30 ATP4− + 36 H2O
Glucose oxidation in eukaryotes takes place in four stages (see Figure 1, top): Stage I: Glycolysis In the cytosol, one 6-carbon glucose molecule is converted by a series of reactions to two 3-carbon pyruvate molecules; a net of 2 ATPs are produced for each glucose molecule.
Stage II: Citric Acid Cycle In the mitochondrion, pyruvate oxidation to CO2 is coupled to the generation of the high energy electron carriers NADH and FADH2, which store the energy for later use. These two carriers can be considered the sources of high-energy electrons.
Stage III: Electron-Transport Chain High-energy electrons flow down their electric potential gradient from NADH and FADH2 to O2 via membrane proteins that convert the energy released into a proton-motive force (H+ gradient). The energy released from the electrons pumps protons across a membrane, thus generating the gradient.
Stage IV: ATP Synthesis The proton-motive force powers the synthesis of ATP as protons flow down their concentration and voltage gradients through the ATP-synthesizing enzyme ATP synthase, which is embedded in a mitochondrial membrane. For each original glucose molecule, an estimated 28 additional ATPs are produced by this mechanism of oxidative phosphorylation.
