The biocatalyst sulfite oxidase causes the conversion of toxic sulfur compounds from the breakdown of amino acids into nontoxic sulfates. It is essential for life and is therefore found in all organisms. If its function is disturbed by a genetic defect, sulfite oxidase deficiency occurs. Even in otherwise healthy patients, too much sulfite in the blood can have a negative effect.
What is sulfite oxidase?
Sulfite oxidase (gene name: SUOX) is the name of a molybdenum-containing enzyme consisting of 466 amino acids. It belongs to the xanthine dehydrogenase family and is found in almost all organisms. It contains molybdenum, a vital trace element, at its center. The metal occurs there in its bioavailable form as a molybdate anion. Sulfite oxidase uses it as a cofactor (molybdate-molybdopterin compound). The enzyme converts the sulfur-containing amino acids methionine, cysteine, etc., ingested through the diet into harmless sulfur salts (sulfates), which are then excreted in the urine. In mammals, the sulfur-degrading biocatalyst is found primarily in the liver and kidneys. The enzyme sulfite oxidase ensures that the blood oxygen combines with the essential amino acids and other sulfur substances. The electrons released in this process are used to generate ATP (adenosine triphosphate) via the electron transport chain. The enzyme catalyzes 10 times the amount of sulfites contained in a liter of alcohol each day.
Function, action, and tasks
Everyone consumes sulfur-containing proteins and food additives on a daily basis. The latter are contained, for example, in pickled vegetables, grapefruit juice, etc., and are intended to protect food from microbial infestation and discoloration. In wine, they form bouquet substances. The breakdown of cysteine alone produces 1680 mg of toxic sulfite in the body every day, which must be converted immediately by sulfite oxidase to prevent damage to organs and tissue. In this process, the enzyme works together with other biocatalysts. Sulfites are toxic and, even in the smallest amounts, can destroy vital substances in the body and inhibit necessary metabolic processes. In order to carry out the important detoxification of cells, sulfite oxidase requires the trace element molybdenum. A deficiency of this metal can lead to serious consequences. Excessive mercury levels in the body can also inhibit the functionality of sulfite oxidase.
Formation, occurrence, properties, and optimal values
Sulfite oxidase is mainly formed in mitochondria, the “energy centers” of cells. In rats, for example, 80 percent of it occurs in liver cell mitochondria. In addition, it is still strongly present in the cells of the kidneys. The molybdenum oxide necessary for the activity of sulfite oxidase is located in the active site of the enzyme. As scientists recently discovered, it can be replaced by molybdenum trioxide nanoparticles in patients with molybdenum deficiency. They have a similar catalytic effect in the body as the natural enzyme. In this way, previously fatal diseases such as sulfocysteinuria could be treated.
Diseases and disorders
A deficiency of sulfite oxidase can cause asthmatic and even anaphylactic reactions in otherwise healthy people by causing the parasympathetic nervous system to affect the mast cells responsible for causing allergies. In addition, low levels of sulfite oxidase can cause severe fatigue, headaches and low blood sugar levels. However, the genetic deficiency of the vital enzyme has even worse consequences. The newborn is born with physical deformities and mental retardation. This so-called sulfite oxidase deficiency or sulfocysteinuria occurs as a molybdenum cofactor (MoCo) deficiency disease in an estimated one in 100,000 to 500,000 births. Infants suffering from isolated sulfite oxidase deficiency show similar symptoms: severe encephalopathy, barely controllable seizures, spasticity, microcephaly, muscle flaccidity, and progressive brain atrophy. Since the autosomal recessive enzyme deficiency disease cannot yet be effectively treated, the young patients usually die in infancy: the undegraded sulfurous compounds poison neurons and myelin sheaths of the central nervous system and accumulate in the cell tissue. Already after birth, problems with food intake and vomiting of the stomach contents occur.The infants are born with deformed skull (protruding forehead, deep-set eyes, overlong palpebral fissures, thick lips, small nose). In the course of the first months of life, the lens in the eye becomes displaced. About 75 percent of the cases of sulfocysteinuria described to date are due to MoCo deficiency: All three enzymes involved in sulfur degradation in the body, sulfite oxidase, xanthine oxidase and aldehyde oxidase, show greatly reduced activity. A mutation in the SUOX gene (chromosome 12) is to blame for the isolated sulfite oxidase deficiency. It manifests in three variants: Type A (mutation in the MOCS1 gene), Type B (MOCS2 gene), and Type C (MOCS3 gene). The type A mutation is the most common. In this case, the formation of the precursor molecule cPMP is inhibited. However, the substance can now be produced and administered in the laboratory. To improve the survival of the child patient, the deficiency disease should be diagnosed as soon as possible and treated with daily intravenous administrations of molybdate. This can at least curb further damage. The child is given anticonvulsant drugs to counteract the seizures. He also has to follow a low protein diet. Alternatively, MoCo precursor Z can be administered. This reduces the seizures and prevents further brain damage. Medical researchers have high hopes for treating the previously incurable disease with molybdenum trioxide nanoparticles, which take over the role of sulfite oxidase in the body. To find out if the unborn baby has sulfite oxidase deficiency, pregnant women can have their S-sulfocysteine levels tested in amniotic fluid.
