No abstract

AMP deaminase (AMPD; EC 3.5.4.6) is encoded by a multigene family in mammals. The AMPDI gene is expressed at high levels in skeletal muscle, where this enzyme is thought to play an important role in energy metabolism. Deficiency of AMPD activity in skeletal muscle is associated with symptoms of a metabolic myopathy. Eleven unrelated individuals with AMPD deficiency were studied, and each was shown to be homozygous for a mutant allele characterized by a C -. T transition at nucleotide 34 (codon 12 in exon 2) and at nucleotide 143 (codon 48 in exon 3). The C -* T transition at codon 12 results in a nonsense mutation predicting a severely truncated AMPD peptide. Consistent with this prediction, no immunoreactive AMPD1 peptide is detectable in skeletal muscle of these patients. This mutant allele is found in 12% of Caucasians and 19% of African-Americans, whereas none of the 106 Japanese subjects surveyed has this mutant allele. We conclude from these studies that this mutant allele is present at a sufficiently high frequency to account for the 2% reported incidence of AMPD deficiency in muscle biopsies. The restricted distribution and high frequency of this doubly mutated allele suggest it arose in a remote ancestor of individuals of Western European descent.

No abstract

D-ribose was administered orally or intravenously over at least 5 h to eight healthy volunteers and five patients with myoadenylate deaminase deficiency. Intravenous administration rates were 83, 167, and 222 mg/kg/h, which were well tolerated but oral administration of more than 200 mg/kg/h caused diarrhea. The average steady state serum ribose level ranged between 4.8 mg/100 ml (83 mg/kg/h, oral administration) and 81.7 mg/100 ml (222 mg/kg/h, intravenous administration). Serum glucose level decreased during ribose administration. The intestinal absorption rate of orally administered ribose was 87.8%-99.8% of the intake at doses up to 200 mg/kg/h without first pass effect. Urinary losses were 23% of the intravenously administered dose at 222 mg/kg/h. Ribose appeared to be excreted by glomerular filtration without active reabsorption; a renal threshold could not be demonstrated. The amount of ribose transported back from the tubular lumen depended on the serum ribose level. There was no difference in ribose turnover in healthy subjects and patients with MAD deficiency.