Xanthine oxidase is responsible for converting purines into uric acid during their breakdown. Deficiency or inhibition of the enzyme results in lowered uric acid levels in the blood.
What is xanthine oxidase?
Xanthine oxidase is an enzyme that initiates (catalyzes) the reaction of hypoxanthine over xanthine to uric acid. It contains a non-protein moiety as a so-called prosthetic (Greek, prosthetos, attached) group that is responsible for the reactivity. This is a flavin derivative. Xanthine oxidase thus belongs to the flavin enzymes. It also has iron and molybdenum in the active site. In 1902, the enzyme was described for the first time as a component of cow’s milk by the biochemist F. Schardinger, so it used to be called the Schardinger enzyme. Under the action of this enzyme, there is a color change of the dye methylene blue, which can be used as a typical detection reaction for distinguishing raw and heat-treated milk. At high temperature, the enzyme is destroyed. The color change is due to the fact that enzymes present in raw milk (such as xanthine oxidase) decolorize methylene blue in the presence of formaldehyde when exposed to air.
Function, action, and roles
Best known task of xanthine oxidase is the formation of uric acid within purine metabolism. Purines are present in every cell. They are components of the nucleic bases adenosine and guanine, which, together with the pyrimidine bases cytosine and thymine (and uracil, respectively), make up the nucleic acids DNA and RNA. The genetic information in the various cells of the body consists of nucleic acids. This is true for humans and for animals. Thus, humans ingest a large amount in the form of animal foods with meat products. If the body’s own cells perish or animal cells that enter the body through food are broken down, nucleic acids and thus purines are produced. These are converted into uric acid. Under the action of xanthine oxidase, hypoxanthine is formed first and, in a further step, xanthine, which is converted into uric acid, can be largely excreted by the kidneys. Only a small proportion of uric acid leaves the body via the intestine. If large amounts of purine accumulate in the body or if excretion via the urine is limited, the uric acid level in the blood increases. A second enzyme involved in purine breakdown also produces uric acid. It is called xanthine dehydrogenase, uses nicotinamide adenine dinucleotide (NAD), and is the predominant enzyme. Xanthine oxidase, on the other hand, has a flavin adenine dinucleotide (FAD) subunit. In the case of a reduced supply, for example due to a lack of blood circulation, both enzymes can convert into each other. During the conversion under the action of xanthine oxidase, hydrogen peroxide is also formed as a by-product. Hydrogen peroxide is not itself a radical, but it is nevertheless a reactive substance. Therefore, it is rapidly rendered harmless by the action of other enzymes (peroxidase, catalase) in the body.
Formation, occurrence, properties and optimal values
Purine breakdown occurs mainly in the liver. In the mucosa of the small intestine, the enzyme is also involved in the incorporation of iron into the transport protein transferrin. Studies have shown that the enzyme is found in cells located in the inner wall of blood vessels. In this context, its influence on the course of cardiovascular diseases and on damage caused by oxidative stress is discussed. The proportion of oxidase in relation to dehydrogenase as the enzyme system responsible for the conversion of purines to uric acid is 20 percent. The xanthine dehydrogenase form is present at 80 percent. The flavin contained in xanthine oxidase is one of the riboflavins, which is identical to vitamin B2. The molybdenum subunit contained in xanthine oxidase is bound by allopurinol, which strongly resembles purines in structure. In this way, the enzyme is almost completely inhibited. The activity of the enzyme can be determined indirectly by the amount of uric acid formed.
Diseases and disorders
During purine-rich meals or during increased cell death, which occurs during cancer therapy, for example, the xanthine oxidase reaction is activated and larger amounts of uric acid are formed. The uric acid level in the blood increases. If the enzyme is inhibited, the uric acid concentration in the blood decreases. This effect underlies the medication in gout disease.In gout, the elevated uric acid concentrations lead to crystallization and thus to discomfort in the joints. Drugs containing allopurinol are standard preparations for the treatment of gout. In the hereditary form of the enzyme deficiency, the activity is reduced by mutations. This disease is inherited autosomal recessively. The child becomes ill if both parents carry an affected allele. Decreased activity of xanthine oxidase also occurs when the molybdenum cofactor is deficient because it is not formed due to a defect. Xanthine and hypoxanthine accumulate. Significantly elevated xanthine levels in the blood and the appearance of xanthine in the urine (xanthinuria) are conspicuous in affected individuals. When xanthine is determined to detect an enzyme deficiency, foods such as coffee beans, tea, mate or potatoes must be excluded as sources of xanthine. Uric acid levels, on the other hand, are decreased. Since xanthine is not broken down and is poorly soluble, it can form crystals. In most cases, the condition is asymptomatic. In others, however, it can lead to kidney problems, urinary tract infections or blood in the urine. If xanthine stones form in severe cases, they can be deposited in the kidney tissue or in the urinary tract. Affected individuals must be careful to follow a low-purine diet and drink plenty of fluids.