TY - JOUR
T1 - Effects of the uricogenic agent, 2-ethylamino-1,3,4-thiadiazole in hypoxanthine-guanine phosphoribosyl transferase deficiency
AU - Nyhan, William L.
AU - Sweetman, Lawrence
AU - Lesch, Michael
N1 - Funding Information:
This investigation was supported by Public Health Service Research Grants HD 02609 from the National Institute of Child Health and Human Development and FR 00261 from the General Clinical Research Centers Branch, Division of Research Facilities and Resources, National Institutes of Health. Received for publication Janua y 17, 1968.
PY - 1968/10
Y1 - 1968/10
N2 - The effects of 2-ethylamino-1,3,4-thiadiazole have been assessed in two patients with a disorder of uric acid metabolism and cerebral function. Patients with this inborn error of metabolism have marked overproduction of purine, and absent activity of hypoxanthine, guanine phosphoribosyl transferase. It was found that this uricogenic thiadiazole increased further, the elevated concentrations of uric acid in blood and urine. Clinical reactions were dramatic, required vigorous therapy, and suggested that the investigation of this compound should not be undertaken lightly in patients with this disease. There was an increase in the cumulative conversion of 14C-labeled glycine into urinary uric acid. These observations indicate that the increased de novo purine synthesis of this condition is capable of further increase. They suggest the possibility that the overproduction of purine found in the disease and that which follows thiadiazoles, are both related to the role of guanine nucleotide in the feedback regulation of purine synthesis.
AB - The effects of 2-ethylamino-1,3,4-thiadiazole have been assessed in two patients with a disorder of uric acid metabolism and cerebral function. Patients with this inborn error of metabolism have marked overproduction of purine, and absent activity of hypoxanthine, guanine phosphoribosyl transferase. It was found that this uricogenic thiadiazole increased further, the elevated concentrations of uric acid in blood and urine. Clinical reactions were dramatic, required vigorous therapy, and suggested that the investigation of this compound should not be undertaken lightly in patients with this disease. There was an increase in the cumulative conversion of 14C-labeled glycine into urinary uric acid. These observations indicate that the increased de novo purine synthesis of this condition is capable of further increase. They suggest the possibility that the overproduction of purine found in the disease and that which follows thiadiazoles, are both related to the role of guanine nucleotide in the feedback regulation of purine synthesis.
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U2 - 10.1016/0026-0495(68)90149-2
DO - 10.1016/0026-0495(68)90149-2
M3 - Article
C2 - 4877987
AN - SCOPUS:0014342462
SN - 0026-0495
VL - 17
SP - 846
EP - 853
JO - Metabolism
JF - Metabolism
IS - 10
ER -