Question

Gout is a disease characterized by hyperuricemia from an overproduction of purine nucleotides via the de novo pathway. The specific cause of Lesch-Nyhan syndrome is a severe deficiency of HGPRTase. Allopurinol is used in the treatment of gout to reduce the production of uric acid. In Lesch-Nyhan syndrome, the decrease in uric acid is balanced by an increase in xanthine plus hypoxanthine in blood. In the other forms of gout, the decrease in uric acid is greater than the increase in xanthine plus hypoxanthine. The explanation for this difference in the two forms of gout is A. it is an experimental artifact and the decrease in uric acid and increase in xanthine plus hypoxanthine in non-Lesch-Nyhan gout is the same. B. allopurinol is less effective in non-Lesch-Nyhan gout. C. there is an increased excretion of xanthine and hypoxanthine in non-Lesch- Nyhan gout. D. PRPP levels are reduced in Lesch-Nyhan. E. in non-Lesch-Nyhan gout hypoxanthine and xanthine are salvaged to IMP and XMP and inhibit PRPP amidotransferase.

Short answer

Question: Explain the difference in the effects of allopurinol in the cases of Lesch-Nyhan syndrome and non-Lesch-Nyhan gout. Answer: The difference in the effects of allopurinol in the two forms of gout is due to the difference in purine salvage. In non-Lesch-Nyhan gout, hypoxanthine and xanthine are salvaged to IMP and XMP, which inhibit PRPP amidotransferase, leading to a greater decrease in uric acid levels compared to Lesch-Nyhan syndrome.

Step-by-step solution

Understand the role of allopurinol in treating gout

Allopurinol is a drug used to decrease the production of uric acid, which is the primary cause of gout. It works by inhibiting the enzyme xanthine oxidase, responsible for the conversion of hypoxanthine to xanthine, and xanthine to uric acid. As a result, the conversion of these compounds is reduced, and the production of uric acid decreases.

Understand Lesch-Nyhan syndrome

Lesch-Nyhan syndrome is characterized by a severe deficiency of HGPRTase (hypoxanthine-guanine phosphoribosyltransferase), an enzyme involved in the purine salvage pathway. This deficiency leads to increased de novo purine synthesis and a higher production of uric acid, resulting in hyperuricemia.

Compare Lesch-Nyhan and non-Lesch-Nyhan gout

In both Lesch-Nyhan and non-Lesch-Nyhan gout, allopurinol is used to reduce the production of uric acid. However, there are differences in their responses to the treatment. In Lesch-Nyhan syndrome, the decrease in uric acid is balanced by an increase in xanthine and hypoxanthine, while in other forms of gout, the decrease in uric acid is greater than the increase in xanthine and hypoxanthine. Now let's analyze the possible explanations (A to E) for this difference:

Evaluate answer choices

A. The fact that Lesch-Nyhan syndrome is caused by a severe deficiency of HGPRTase provides evidence that it is not just an experimental artifact, and the difference between the two responses exists. B. Allopurinol inhibits xanthine oxidase in both cases, so there is no reason to believe that it would be less effective in non-Lesch-Nyhan gout. C. This statement is consistent with the observed data, as an increased excretion of xanthine and hypoxanthine in non-Lesch-Nyhan gout would lead to higher blood levels of these compounds. D. PRPP levels could be reduced in Lesch-Nyhan, but that wouldn't explain the difference in the response to allopurinol treatment. E. This statement suggests that, in non-Lesch-Nyhan gout, hypoxanthine and xanthine are salvaged to IMP and XMP, which inhibit PRPP amidotransferase, a key enzyme in purine synthesis. This could potentially lead to decreased purine synthesis and a greater decrease in uric acid levels compared to Lesch-Nyhan syndrome. From the evaluation of answer choices, statement E is the most reasonable explanation for the observed difference between Lesch-Nyhan and non-Lesch-Nyhan gout in their response to allopurinol treatment. Conclusion: The best explanation for the difference in the two forms of gout is option E. In non-Lesch-Nyhan gout, hypoxanthine and xanthine are salvaged to IMP and XMP, which inhibit PRPP amidotransferase, leading to a greater decrease in uric acid levels compared to Lesch-Nyhan syndrome.