Causes of purine metabolism disorders

The disease of purine metabolism disorder is still very complicated. Many people are not clear about the reasons why they have this problem, so there is no way to achieve good treatment effects in the first time. When necessary, it may also cause increased uric acid. Although it will not immediately cause a series of symptoms to the body, it will gradually damage the inside of the body, which will lead to more diseases. Relevant treatment measures must be taken as soon as possible.

reason:

Excessive uric acid in the blood

Defects in certain enzymes involved in purine metabolism can cause increased uric acid levels, such as:

① Abnormalities in PRPP synthase can lead to increased PRPP synthesis and uric acid production.

②HGPRT enzyme deficiency can be complete deficiency (such as Lesch-Nyhan syndrome, see gout) or incomplete deficiency. This enzyme catalyzes the recycling of guanine, hypoxanthine and PRPP into corresponding nucleotides, thereby controlling the conversion of guanine and hypoxanthine into xanthine and then the amount of uric acid produced. When the activity of this enzyme decreases, this control is lost and uric acid is produced in large quantities. Clinical manifestations are hyperuricemia and gout.

③6-phosphoglucose deficiency is seen in glycogen storage disease type I, with severe hypoglycemia and acidosis, causing hyperuricemia and increased uric acid. Congenital hyperactivity of all or part of the enzyme reactions in the purine metabolic pathway (such as structural variation of PRPP synthase, which increases its activity by 3 times) also leads to the massive production of uric acid, the final product. Patients not only have hyperuricemia, but also hyperuricosuria. The clinical manifestations are uric acid excess gout, paroxysmal joint pain, arthritis, joint deformity, kidney damage, and gouty nodule formation.

Too little uric acid in the blood

It is caused by excessive excretion or reduced production of urate and uric acid. Genetic defects or severe liver disease cause xanthine oxidase deficiency, which impairs the metabolism of hypoxanthine into xanthine or xanthine into uric acid, resulting in insufficient formation of uric acid in the blood and increased excretion of hypoxanthine and xanthine. Severe patients may develop xanthineuria and xanthine stones. Purine nucleotide phosphorylase deficiency prevents inosine and guanine from being converted into hypoxanthine and guanine. As a result, excessive purine nucleosides are excreted in the urine, which may cause kidney stones.

There is another important step in purine metabolism, which is the purine recycling synthesis pathway. The purines produced by the decomposition of nucleotides can be recycled. Adenine and PRPP can synthesize AMP under the action of adenine phosphoribosyltransferase (APRT, E in the figure). Hypoxanthine, guanine and PRPP can be recycled and synthesized into IMP and GMP respectively under the action of hypoxanthine guanine phosphoribosyltransferase (HGPRT, E in the figure). This can also control the production of uric acid. When these enzymes are deficient, this control is lost and a large amount of uric acid is produced (see Figure [Purine synthesis and decomposition pathways and synthesis feedback regulation]). The clinical manifestations of purine metabolism disorders can be manifested as excessive or low blood uric acid.