Aldehyde Oxidase: Function & Diseases

Aldehyde oxidase represents an enzyme that degrades aldehydes in vertebrates. It is found in various tissues of mammals and humans. The exact function of aldehyde oxidase is not yet known.

What is aldehyde oxidase?

Aldehyde oxidase (AOX1) helps in the enzymatic breakdown of aldehydes in the body. However, it has also been found to break down nicotine to cotinine. In this process, 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 for 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 that can encode a functional enzyme. In other vertebrates, several AOX genes are active. Aldehyde oxidase is very similar and related to the enzyme xanthine dehydrogenase. Both enzymes can be used to convert hypoxanthine to xanthine with the inclusion of an oxygen atom and water molecule. However, the conversion of xanthine to uric acid is only carried out by xanthine hydrogenase (xanthine oxidase). Aldehyde oxidase consists of 1338 amino acids. Molybdopterin, FAD and 2(2Fe2S) serve as cofactors for its effectiveness. The reaction, already characterized by its name, marks the conversion of aldehydes to carboxylic acids and hydrogen peroxide with the addition of oxygen and water.

Function, action, and tasks

The enzyme aldehyde oxidase catalyzes several reactions. In large part, it is responsible for the conversion of aldehydes to carboxylic acids with the addition of oxygen and water. In general, aldehyde oxidase mediates the addition of an oxygen atom to a substrate. Among other things, it also catalyzes the conversion of nicotine to conitine. Therefore, it also plays a major role in biotransformation and tryptophan metabolism. In these reactions, molybdenum is always necessary as a cofactor. In biotransformation, it converts xenobiotics with aldehyde groups into the corresponding carboxylic acids in the phase I reaction. Glucuronic acid is added to the carboxyl groups in the phase II reaction to increase water solubility and flush 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 addition of oxygen and water is catalyzed 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 (proliferation of fat cells). In this process, it stimulates the release of the tissue hormone adiponectin. Adiponectin in turn increases the effectiveness of insulin. In hepatocytes, adiponectin in turn inhibits the release of aldehyde oxidase. Deficiency of aldehyde oxidase (AOX1) also inhibits lipid export from cells. The exact function of aldehyde oxidase is not fully understood.

Formation, occurrence, properties, and optimal levels

Aldehyde oxidase is found mainly in the cytoplasm of liver cells. However, it is also found in adipose cells, lung tissue, skeletal muscle, and the pancreas. It used to be confused with the homologous xanthine oxidase. Although both enzymes are structurally similar. However, they catalyze partially different reactions. However, both enzymes 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 and disorders

Along 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 results in deficient function of these three enzymes. Xanthine dehydrogenase catalyzes the breakdown of xanthine 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. If this enzyme is deficient, sulfite is no longer converted into sulfate. Due to the cofactor molybdenum, the three enzymes are usually jointly deficient. Of course, isolated defects due to mutations are possible for each of these enzymes. However, no clinical picture with a specific aldehyde oxidase deficiency has been described so far. Molybdenum deficiency induced by an unbalanced diet is again very rare. However, this can occur with more than six months of molybdenum-deficient parenteral nutrition. In such cases, tachypnea, tachycardia, severe headache, nausea, vomiting, central facial deficits, or coma often occur. Furthermore, intolerance to certain amino acids occurs. Increased sulfite concentrations are found in the urine, while decreased uric acid levels occur in the blood. If the molybdenum deficiency persists for a long time, there may be problems with the breakdown of sulfur-containing amino acids, sulfite allergies, hair loss, low uric acid levels in the blood, and fertility problems. However, most symptoms are due to sulfite oxidase and xanthine dehydrogenase deficiency. Tachycardia is probably due to increased levels of epinephrine or norepinephrine (catecholamines), as their breakdown is delayed by aldehyde oxidase deficiency. Molybdenum deficiency can be caused by extremely low molybdenum diets and inflammatory bowel diseases such as Crohn’s disease with malabsorption of food. Hereditary molybdenum cofactor deficiency due to impaired synthesis of molybdopterin is fatal due to complete failure of all three enzymes without treatment.