Use of phytohaemagglutinin stimulated lymphocytes to study effects of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency on polynucleotide and protein synthesis in the Lesch-Nyhan syndrome.
AUTOR(ES)
McKeran, R O
RESUMO
The incorporation of [14C]thymidine and [14C]uridine into the nucleoprotein, and [14C]phenylalanine into the protein by phytohaemagglutinin (PHA) stimulated lymphocytes from a patient with the Lesch-Nyhan syndrome [hypoxanthine-guanine phosphoribosyl transferase (EC 2.4.2.8 HGPRT) deficiency] and controls, was studied over 72 hours of incubation, with and without azaserine to block de novo purine biosynthesis. No difference was observed between the values obtained for Lesch-Nyhan and control lymphocytes, when PHA-stimulated without added azaserine. The percentage reduction in the incorporation of precursors into nucleoprotein and protein after PHA stimulation in the presence of azaserine was more obvious in the lymphocytes of the patient with the Lesch-Nyhan syndrome than in the controls after the shorter incubation periods at the lower rates of synthesis. Blocking the de novo purine biosynthetic pathway, in control PHA stimulated lymphocytes, inhibited transformation, whereas loss of the purine salvage enzyme HGPRT did not have this effect. These results are compatible with the view that the brain and bone-marrow damage that occur in the Lesch-Nyhan syndrome are the result of lack of HGPRT in tissues with little de novo purine biosynthetic capability. Other tissues with both pruine biosynthetic and salvage pathways are less vulnerable to the enzyme defect. Some possible mechanisms by which HGPRT deficiency could act are discussed. We suggest that inability to increase the supply of guanylic acid (GMP) in response to a mitotic stimulus may mediate the effect of HGPRT deficiency.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1013367Documentos Relacionados
- Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in a patient with the Lesch-Nyhan syndrome.
- Identification of a single nucleotide change in the hypoxanthine-guanine phosphoribosyltransferase gene (HPRTYale) responsible for Lesch-Nyhan syndrome.
- Hypoxanthine-guanine phosphoribosyltransferase: characteristics of the mutant enzyme in erythrocytes from patients with the Lesch-Nyhan syndrome
- THE PURINE REQUIREMENT OF CELLS CULTURED FROM HUMANS AFFECTED WITH THE LESCH-NYHAN SYNDROME (HYPOXANTHINE-GUANINE PHOSPHORIBOSYLTRANSFERASE DEFICIENCY)*
- Dietary-Induced Variation of Hypoxanthine-Guanine Phosphoribosyl Transferase Activity in Patients with the Lesch-Nyhan Syndrome