Dehydrogenases are enzymes involved in oxidation processes. They occur in the human body in different variants and catalyze, for example, the breakdown of alcohol in the liver.
What are dehydrogenases?
Dehydrogenases are specialized enzymes. These biocatalysts accelerate the natural oxidation of substrates. A substance that oxidizes loses electrons. In biological reactions, dehydrogenases split hydrogen anions from a substrate. Anions are negatively charged particles. In this case, a hydrogen atom accepts an electron and thus acquires a negative electrical charge. The actual reaction takes place at the active site of the enzyme. When the dehydrogenase cleaves the hydrogen anion from a substrate, cofactors accept the electrons and hydrogen. Cofactors are molecules that play a helping role in enzymatic processes but are not involved in the cleavage itself. The cofactors of dehydrogenases include nicotinamide adenine dinucleotide (NAD+) and flavin adenine dinucleotide (FAD). Unlike dehydrogenases, dehydratases cleave whole water molecules from their substrate. Dehydrogenases can also cause the opposite reaction, contributing to reduction rather than oxidation. In reduction, a particle accepts electrons instead of donating them. Biology classifies dehydrogenases as oxide reductases. This type of enzyme exists in every living organism.
Function, action, and tasks
Dehydrogenases form a group composed of numerous specialized enzymes. The individual enzymes have different tasks in the human body. Biology further subdivides the various dehydrogenases into subgroups. Aldehyde dehydrogenases (ALDH), for example, form a group of dehydrogenases found primarily in the liver. As a rule, an ALDH is only responsible for a specific substrate and cannot participate in the oxidation of other substrates. ALDH1A1, -1A2 and -1A3, for example, process retinal, which is found in vitamin A. However, there are exceptions to this rule: ALDH2, for example, can work with different substrates and is not limited to one substance. In the liver, dehydrogenases break down alcohol, for example ethanol. They thereby participate in the purification of blood, which is one of the most important tasks of the liver. The ethanol molecule first docks onto the active site of an alcohol hydrogenase (ADH). With the help of the enzyme, the ethanol oxidizes by splitting off the negatively charged hydrogen atom and releasing it to its cofactor NAD+: ADH converts ethanol into acetaldehyde in this way. Acetaldehyde or ethanal is toxic and triggers a number of health complaints. Normally, food contains little ethanol, which the body can convert quickly. Therefore, the amounts of ethanal are also small. Acetaldehyde, in turn, provides the substrate for ALDH. ALDH catalyzes the conversion of acetaldehyde to acetic acid before the acetic acid can be further cleaved and broken down into water and carbon dioxide. In this form, the molecules are completely harmless.
Formation, occurrence, properties and optimum values
The dehydrogenases are mostly found in the liquid parts of the cell plasma or in the mitochondria. Women’s bodies produce less ADH than men’s bodies. This contributes to the fact that women are on average more sensitive to alcohol. The exact levels of the various dehydrogenases vary not only between different enzyme groups, but also between different individuals and ethnic groups. In East Asia and among the indigenous peoples of the Americas and Australia, levels of ADH are lower on average than among Europeans, for example. The human genome has 19 known genes that determine ALDH. These genes are located on the twelfth chromosome. They determine the sequence of amino acids within protein chains. This sequence in turn determines the properties of protein structures. The shape of the dehydrogenases and thus their function also depends on the sequence of amino acids during synthesis. ALDH2, for example, consists of 500 amino acids. As a rule, cells synthesize dehydrogenases that they also need later; this eliminates the need to transport the substances.
Diseases and disorders
When alcohol is broken down in the human body, acetaldehyde is formed as an intermediate.The substance is toxic; the enzyme ALDH must therefore convert it into acetic acid as quickly as possible. With larger amounts of alcohol, however, this is usually not completely successful. A few hours after alcohol consumption, therefore, the hangover remains. Medicine also refers to it as veisalgia. Typical symptoms are headache, malaise, a sinking feeling in the stomach, vomiting and loss of appetite. The ability to concentrate and react is often impaired. How sensitive people are to alcohol depends, among other things, on how many dehydrogenases the liver cells produce. Dehydrogenases also play a role in the development or maintenance of various diseases. Fatty aldehyde dehydrogenase (FALDH), for example, occupies a central position in the development of Sjögren’s syndrome. The core symptoms of the syndrome are mental retardation and progressive spastic paraplegia. Spastic paraplegia is a neurodegenerative disorder and is characterized by spastic paralysis in the legs. Sjögren-Larsson syndrome also causes the horny layer of the skin to become more pronounced and form clearly visible skin scales (ichthyosis). In addition to these three cardinal symptoms, disorders of the retina are common. The cause of the syndrome lies in the genes that encode FALDH. Due to a mutation, the body does not correctly synthesize the enzyme complex containing FALDH. As a result, the concentration of fatty alcohols and fatty aldehydes in the blood plasma increases.
