Regulation of nicotinamide-adenine dinucleotide synthesis in erythrocytes of patients with hypoxanthine-guanine phosphoribosyltransferase deficiency and a patient with phosphoribosylpyrophosphate synthetase superactivity.

Abstract

1. The synthesis of nicotinamide-adenine dinucleotide from nicotinamide and nicotinic acid was compared over different time scales at both physiological (0.7 mumol/l) and high (0.2-3 mmol/l) substrate concentrations in erythrocytes from three patients with hypoxanthine-guanine phosphoribosyltransferase (hypoxanthine phosphoribosyltransferase, EC 2.4.2.8) deficiency (including one Lesch-Nyhan patient) and from one patient with phosphoribosylpyrophosphate synthetase superactivity. The above disorders are associated with grossly altered erythrocyte nicotinamide-adenine dinucleotide levels. 2. At the physiological substrate concentration and incubation times up to 2 h, nicotinamide proved the most efficient nicotinamide-adenine dinucleotide precursor for erythrocytes from both patients and control subjects. The conversion of nicotinamide to its mononucleotide, but not further metabolism, was impaired in phosphoribosylpyrophosphate synthetase-mutant cells. The Lesch-Nyhan and phosphoribosylpyrophosphate synthetase-mutant cells were unusual in that both showed no further stimulation of nucleotide synthesis at 18 mmol/l Pi compared with 1 mmol/l. 3. At the high substrate concentrations, using 18 mmol/l Pi, nicotinamide was a poor precursor in all instances. Using nicotinic acid, nucleotide formation was 30-fold that from nicotinamide, reaching its maximum at 0.2 mmol/l. Conversion of nicotinic acid to nicotinamide-adenine dinucleotide in the phosphoribosylpyrophosphate synthetase-mutant cells was again grossly impaired. 4. There was no evidence for increased nicotinamide-adenine dinucleotide breakdown in the phosphoribosylpyrophosphate synthetase-mutant cells under any of the above conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: V Micheli, H A Simmonds, C Ricci
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 78 Issue 2 Pg. 239-45 (Feb 1990) ISSN: 0143-5221 [Print] England
• PMID: 2155755 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nicotinic Acids
• NAD
• Niacinamide
• Hypoxanthine Phosphoribosyltransferase
• Phosphotransferases
• Ribose-Phosphate Pyrophosphokinase

Topics

• Adult
• Cells, Cultured
• Child
• Chromatography, High Pressure Liquid
• Erythrocytes (metabolism)
• Female
• Humans
• Hypoxanthine Phosphoribosyltransferase (deficiency)
• Lesch-Nyhan Syndrome (metabolism)
• Male
• Metabolism, Inborn Errors (metabolism)
• NAD (biosynthesis)
• Niacinamide (metabolism)
• Nicotinic Acids (metabolism)
• Phosphotransferases (metabolism)
• Ribose-Phosphate Pyrophosphokinase (metabolism)