Respiratory Chain: Function, Role & Diseases

The respiratory chain is the name given to a cascade of electron transfer steps (redox reactions) in the metabolism of the cells of almost all living organisms. At the end of the respiratory chain, which occurs in the mitochondria, the powerhouses of cells, ATP (adenosine triphosphate) and water (H2O) are produced. ATP contains the conserved energy that can be transported over short distances, which comes from the respiratory chain and is available for endothermic, or energy-requiring, metabolic processes.

What is the respiratory chain?

ATP and water are produced at the end of the respiratory chain, which occurs in mitochondria, the powerhouses of cells. As part of cellular respiration, the respiratory chain involves a chain of sequential redox reactions, electron-donating and electron-accepting reactions that are catalytically controlled by enzymes. The overall highly exothermic process, which corresponds to the combustion of hydrogen to water (oxyhydrogen reaction), would otherwise thermally destroy the cells or even cause them to explode. The respiratory chain takes place in the inner membrane of the mitochondria in four successive redox complexes: The electrons transferred to the next stage each release part of their energy. At the same time, due to the protons (H+) released into the space between the inner and outer membrane (intermembrane space) of the mitochondria, a proton gradient builds up. The protons try to migrate from the area of high concentration to the area of low concentration – in this case the inner membrane. This only works in conjunction with the enzyme ATP synthase, a tunnel protein. During passage through the tunnel protein, the protons release energy, which is converted into ATP in the course of oxidative phosphorylation of ADP (adenosine diphosphate) and inorganic phosphate. ATP serves as an omnipotent energy carrier for almost all energy-consuming metabolic processes in the body. When energy is used in metabolic processes, it is converted back to ADP with exothermic cleavage of a phosphate group.

Function and task

The respiratory chain has the task and function, in conjunction with the citrate cycle that also occurs in the mitochondria, of providing the body with usable energy in sufficient quantities. Ultimately, degradation processes of food components of the substance groups carbohydrates, fats and proteins lead in the last part of the degradation processes to the respiratory chain, in which the energy contained in the food components is made available to the body in the form of energetically usable ATP. The main benefit for the human metabolism is that the chemical energy contained in the food components is not exclusively and uncontrollably converted into heat energy, but is stored in the form of ATP. The ATP allows the body to use the stored energy in a temporally and spatially staggered manner as needed. Almost all energy-consuming metabolic processes rely on ATP as an energy supplier. The respiratory chain comprises four so-called complexes (I, II, III, IV) and additionally as the last step the phosphorylation of ADP to ATP, which is also called complex V by some authors. In both electron transfer chains I and II, enzyme complexes related to ubiquinone, NAD/NADH (nicotinamide adenine dinucleotide) and FAD (flavin adenine dinucleotide) play an important role. The processes at complexes III and IV also occur with the participation of ubiquinol or the oxidized ubiquinone and cytochrome c oxidase, which oxidizes to cytochrome c. At the same time, oxygen is reduced to water (H2O) with the addition of 2 H+ ions. The respiratory chain can be regarded as a kind of open cycle in which the enzymatic catalysts involved are constantly regenerating and intervening anew in the metabolic cycle. This turns out to be particularly energy-efficient for the body’s metabolism and particularly efficient with regard to the use of resources, due to the perfect recycling of the biocatalysts (enzymes) involved.

Diseases and ailments

The respiratory chain involves a cascade of electron transfers involving many substances and, above all, complex enzymatic processes in a kind of biocatalytic process. If any one of these processes is disturbed, the respiratory chain itself can be disrupted or, in extreme cases, completely shut down.In principle, a number of genetic defects can also occur in the chromosome set or as well as genetic defects exclusively in the separate mitochondrial DNA. If there is a mitochondrial genetic defect, it may originate exclusively from the mother, because the separate mitochondrial DNA of the male is located exclusively in the tail of the sperm, which, however, is rejected and excreted before the sperm penetrates the egg. Beyond genetically determined disturbances in the course of the respiratory chain, acquired disturbances are also possible, caused, for example, by natural or artificial inhibitors of the respiratory chain. A number of substances are known that inhibit the respiratory chain at a defined site, so that the respiratory chain is completely interrupted or functions only inadequately. Other substances act as so-called uncouplers (protonophores), which cause the oxidation steps to proceed much faster and lead to an increased oxygen demand. Here, too, there are natural and artificial decouplers. Some antibiotics and fungicides, for example, act as inhibitors, some of which attack complexes I, II or III. The antibiotic oligomycin directly inhibits the ATP synthase process, resulting in reduced ATP synthesis with reduced oxygen consumption. Brown adipose tissue also acts as a natural uncoupler, which is able to convert energy directly into heat without a detour via ATP. Dysfunction in the respiratory chain is usually manifested by decreased performance, as well as frequent or constant fatigue and fatigue.