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Partial deficiency of hypoxanthine‐phosphoribosyltransferase:evidence for a structural mutation in a patient with gout
Author(s) -
GUTENSOHN W.,
JAHN H.
Publication year - 1979
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1979.tb01665.x
Subject(s) - hypoxanthine guanine phosphoribosyltransferase , hypoxanthine phosphoribosyltransferase , phosphoribosyltransferase , hypoxanthine , mutant , chemistry , biochemistry , enzyme , gout , lesch–nyhan syndrome , enzyme assay , adenine phosphoribosyltransferase , microbiology and biotechnology , biology , purine , gene
. A mutant hypoxanthine‐phosphoribosyltransferase (EC 2.4.2.8) from a patient with gout is examined. The activity of the erythrocyte enzyme is about 5% of normal in this case. Immunoprecipitation studies using antiserum against highly purified human hypoxanthine‐phosphoribosyltransferase reveal that the patient's erythrocytes contain a normal amount of cross‐reacting material. The mutant enzyme has an altered net charge as shown by preparative isoelectric focusing (pI values of 5.75 and 4.55). The influence of chemical modification on enzymic activity was studied using a number of different reagents directed against sulfhydryl‐, amino‐, and guanidino‐groups. Compared with normal hypoxanthine‐phosphoribosyltransferase the mutant enzyme shows a generally lowered susceptibility to active site‐directed inhibition. It is concluded that the patient's enzyme is the product of a structural mutation.