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Proposed explanation for S-adenosylhomocysteine hydrolase deficiency in purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase-deficient patients.

Publication ,  Journal Article
Hershfield, MS
Published in: J Clin Invest
March 1981

We have examined the basis for the recently reported, but unexplained deficiency of S-adenosylhomocysteine hydrolase (AdoHcyase) in the erythrocytes of patients with genetic deficiencies of purine nucleoside phosphorylase and hypoxanthine-guanine phosphoribosyltransferase. We found that a hemolysate from a patient with purine nucleoside phosphorylase deficiency had only 7% of control AdoHcyase activity, conforming the original observation. Of the purine nucleosides known to accumulate in nucleoside phosphorylase-deficient patients, inosine alone caused the phosphate-dependent, irreversible inactivation of purified human placental AdoHcyase, and of AdoHcyase in intact erythrocytes and cultured lymphoblastoid cells. Hypoxanthine did not inactivate purified AdoHcyase, but potentiated the effect of inosine in intact hypoxanthine-guanine phosphoribosyltransferase-deficient human lymphoblastoid cells. This presumably resulted from the ability of hypoxanthine to shift the equilibrium of the nucleoside phosphorylase reaction, preventing inosine breakdown. This could account for the partial AdoHcyase deficiency reported in hypoxanthine-guanine phosphoribosyltransferase-deficient patients. We have also demonstrated the AdoHycase-catalyzed synthesis of S-inosylhomocysteine from inosine and L-homocysteine, a reaction which may occur in nucleoside phosphorylase-deficient patients.

Duke Scholars

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 1981

Volume

67

Issue

3

Start / End Page

696 / 701

Location

United States

Related Subject Headings

  • Purine-Pyrimidine Metabolism, Inborn Errors
  • Purine-Nucleoside Phosphorylase
  • Purine Nucleosides
  • Placenta
  • Phosphates
  • Pentosyltransferases
  • Lymphocytes
  • Immunology
  • Immunologic Deficiency Syndromes
  • Hypoxanthine Phosphoribosyltransferase
 

Published In

J Clin Invest

DOI

ISSN

0021-9738

Publication Date

March 1981

Volume

67

Issue

3

Start / End Page

696 / 701

Location

United States

Related Subject Headings

  • Purine-Pyrimidine Metabolism, Inborn Errors
  • Purine-Nucleoside Phosphorylase
  • Purine Nucleosides
  • Placenta
  • Phosphates
  • Pentosyltransferases
  • Lymphocytes
  • Immunology
  • Immunologic Deficiency Syndromes
  • Hypoxanthine Phosphoribosyltransferase