What is aldehyde oxidase?
The aldehyde oxidase (AOX1) helps in the enzymatic degradation of aldehydes in the body. However, it has been found that it also breaks down nicotine to cotinine. In this case, an oxygen atom is incorporated into the oxygen-free nicotine to form an aldehyde structure.
Due to this fact, aldehyde oxidase is also important for tryptophan metabolism and, at the same time, biotransformation. It is mainly found in the cytosol of liver cells, pancreas, lung, skeletal muscle or fat cells. For the activity of the enzyme, the cofactor molybdenum is very important. In human DNA, there is only one AOX gene which can encode a functional enzyme. In other vertebrates several AOX genes are active. Aldehyde oxidase is very similar to and related to the enzyme xanthine dehydrogenase.
With both enzymes hypoxanthine can be converted to xanthine by absorbing an oxygen atom and a water molecule. However, the conversion of xanthine to uric acid is only by xanthine hydrogenase (xanthine oxidase). The aldehyde oxidase consists of 1338 amino acids. The cofactors for their efficacy are molybdopterin, FAD and 2 (2Fe2S). The already characterized by the name reaction characterizes the conversion of aldehydes under supply of oxygen and water to carboxylic acids and hydrogen peroxide.
Function, effect & tasks
The enzyme aldehyde oxidase catalyses several reactions. For the most part, it is responsible for the conversion of aldehydes to carboxylic acids with the supply of oxygen and water. Generally, aldehyde oxidase mediates the addition of an oxygen atom to a substrate.
It catalyzes, among other things, the conversion of nicotine to conitin. Therefore, it also plays a major role in biotransformation and tryptophan metabolism. In these reactions, molybdenum is always necessary as a cofactor. In the context of biotransformation, it converts xenobiotics with aldehyde groups into the corresponding carboxylic acids in the phase I reaction. In the phase II reaction, glucuronic acid is added to the carboxyl groups to increase the water solubility in order to leach the foreign molecule out of the body.
Structurally and chemically, aldehyde oxidase is closely related to the homologous enzyme xanthine hydrogenase (xanthine oxidase). However, why the conversion of xanthine to uric acid with the supply of oxygen and water is catalysed only by xanthine oxidase is not known. The conversion of hypoxanthine to xanthine is still catalyzed by both enzymes. Furthermore, aldehyde oxidase is also responsible for adipogenesis (increase in fat cells).
It stimulates the release of the tissue hormone adiponectin. Adiponectin in turn increases the effectiveness of insulin. In the hepatocytes, adiponectin inhibits the release of aldehyde oxidase. Lack of aldehyde oxidase (AOX1) also inhibits lipid export from the cells. The exact function of aldehyde oxidase is not fully understood.
Education, occurrence, properties & optimal values
Aldehyde oxidase occurs mainly in the cytoplasm of liver cells. However, it is also found in fat cells, lung tissue, skeletal muscle and the pancreas. It used to be confused with homologous xanthine oxidase.
Both enzymes are structurally similar. However, they partially catalyze different reactions. Both enzymes, however, require the same cofactors for their function. These are molybdopterin, FAD and 2 (2Fe2S). However, aldehyde oxidase not only degrades aldehydes, but is also responsible for the oxidation of N-heterocyclic compounds such as nicotine to cotinine.
Diseases & Disorders
Together with xanthine dehydrogenase (xanthine oxidase) and sulfite oxidase aldehyde oxidase is dependent on the cofactor molybdenum. The molybdenum is incorporated as a complex atom in a molybdopterin and forms the molybdenum cofactor. Molybdenum deficiency leads to a defective function of these three enzymes.
Xanthine dehydrogenase catalyzes xanthine degradation to uric acid. The enzyme aldehyde oxidase is only partially involved in this process, for example in the degradation of hypoxanthine to xanthine. Here it even competes with xanthine oxidase. Therefore, there is no isolated aldehyde oxidase deficiency. However, aldehyde oxidase supports the degradation of catecholamines. Sulfite oxidase is responsible for the degradation of sulfur-containing amino acids such as cysteine, taurine or methionine. In the absence of this enzyme, sulfite is no longer converted to sulfate. Due to the cofactor molybdenum, the three enzymes usually have a common deficiency.
Of course isolated mutations are possible by mutations for each of these enzymes. However, so far no disease has been described with a specific aldehyde oxidase deficiency. Again, a one-sided diet-induced molybdenum deficiency is very rare. However, this can happen with a molybdenum-poor parenteral nutrition lasting more than six months. Tachypnea, tachycardia, severe headache, nausea, vomiting, central facial loss, or coma are common in such cases. Furthermore, there are intolerances to certain amino acids. Increased sulfite concentrations are found in the urine, while decreased uric acid levels occur in the blood.
If the molybdenum deficiency lasts for a long time, it can lead to degradation problems of sulfur-containing amino acids, sulfite allergies, hair loss, low uric acid levels in the blood and fertility disorders. However, most of the symptoms are due to sulfite oxidase and xanthine dehydrogenase deficiency. Tachycardia is likely due to increased levels of epinephrine or norepinephrine (catecholamines) as their degradation is delayed by the aldehyde oxidase deficiency. Molybdenum deficiency may be associated with malabsorption of food in extremely low-molybdenum diets and in inflammatory bowel disease such as Crohn's disease.
A hereditary molybdenum cofactor deficiency due to impaired synthesis of molybdopterin is lethal by the complete failure of all three enzymes without treatment.