Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.7 (adenine phosphoribosyltransferase)
 692 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reports the detection of five inherited disorders of purine and one of pyrimidine metabolism using intact red blood cells (RBCs) and compares the findings with those from RBC lysate activity. Two different phosphate levels (1 and 18 mmol L-1 Pi) were used to evaluate endogenous PP-ribose-P levels and their generation by PP-ribose-P synthetase. The importance of this dual approach is demonstrated by the following evidence: (a) Six out of eight patients with no detectable hypoxanthine-guanine phosphoribosyltransferase (HGPRT) RBC lysate activity had up to 25% of normal activity in their intact RBCs. Two Lesch-Nyhan patients showed no detectable activity in intact or lysed RBCs. (b) RBC lysates from two heterozygotes for adenosine deaminase (ADA) deficiency also showed no detectable activity, but up to 60% of normal activity using intact RBCs. (c) The existence of an aberrant enzyme in a kindred with a superactive PP-ribose-P synthetase was evident from the fact that intact RBCs failed to respond normally to phosphate activation, despite normal HGPRT and adenine phosphoribosyltransferase (APRT) RBC lysate activity. (d) Raised endogenous PP-ribose-P levels in intact RBCs were demonstrable only in purine nucleoside phosphorylase (PNP) and HGPRT deficiency; levels were normal in APRT deficiency and hereditary oroticaciduria (OPRT/ODC) deficiency. The results indicate that diagnosis from RBC lysate activity alone may be misleading. Intact RBC studies clearly provide a better indication of the functional capacity of the enzyme in vivo. They also show a closer correlation with the clinical phenotype and allow further insight into the associated biochemical abnormalities in some cases.
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PMID:Use of intact erythrocytes in the diagnosis of inherited purine and pyrimidine disorders. 244 57

Elevated levels of APRT activity are found in erythrocytes from most patients with a primary deficiency of HPRT. A twofold elevation of APRT activity has also been measured in hemolysate from one patient with a deficiency of both OPRT and ODC activity. In an attempt to further define the mechanisms responsible for these apparent alterations in APRT expression, we have studied the catalytic, immunochemical, and electrophoretic properties of APRT in erythrocytes from patients with these inborn errors of purine and pyrimidine metabolism. We have found that the elevated activity of APRT in HPRT-deficient erythrocytes results from an increased amount of a catalytically normal APRT protein. Immunochemical and electrophoretic studies that this APRT protein is structurally normal. One patient with a deficiency of OPRT-ODC demonstrated a fourfold increase in APRT protein; this enzyme was catalytically less efficient than APRT from normal controls.
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PMID:Adenine phosphoribosyltransferase in patients with disorders of purine and pyrimidine metabolism. 706 17