Altered kinetic properties of a mutant adenine phosphoribosyltransferase.
Metabolism
; 35(2): 187-92, 1986 Feb.
Article
em En
| MEDLINE
| ID: mdl-2418331
ABSTRACT
Three siblings in a Japanese family experienced recurrent 2,8-dihydroxyadenine urolithiasis despite the presence of adenine phosphoribosyltransferase (APRT) activities in the hemolysates (19.9% to 28.2% of normal value). However, studies on viable T cells from these patients indicated that APRT was not functional in viable cells. Further analysis of the partially purified enzymes from hemolysates disclosed that patient's APRT had a reduced affinity to 5-phosphoribosyl-1-pyrophosphate (PRPP). Seven healthy members of this family whose APRT functioned normally in viable T cells had the erythrocyte enzyme levels between the patients and normal individuals (38.2% to 65.6%), suggesting that they are carriers of the defective gene. These results indicate that the defective gene code a unique mutant APRT with a reduced affinity to PRPP, and the patients are homozygotes. The mutant enzyme was also shown to be more heat-stable than normal enzyme. However, since mutant enzyme, unlike normal enzyme, was insensitive to the stabilization effect of PRPP, the latter became more heat-stable than the former when the heat treatment was performed in the presence of PRPP. This type of defect with alterations in the kinetic and physical properties of APRT as described here is likely to be a common type of APRT deficiency in Japan.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pentosiltransferases
/
Adenina Fosforribosiltransferase
Limite:
Humans
Idioma:
En
Revista:
Metabolism
Ano de publicação:
1986
Tipo de documento:
Article