Myoadenylate deaminase deficiency studies on normal and deaminase-deficient skeletal muscle

Abstract Two kinetically and regulatory similar isoforms of AMP-deaminase were demonstrated in adult human skeletal muscle. In an extract from normal muscle, 5–10% of the AMP-deaminase activity was released from a phosphocellulose column in the 0.75 mol/l potassium chloride eluate, the remaining activity being eluted with 2.0 mol/l potassium chloride. In a muscle extract from a patient with myoadenylate deaminase deficiency the total AMP-deaminase activity was only 2% of the control, and it eluted mainly in 0.75 mol/l KCl fraction. The AMP-deaminase variant, which eluted with 2.0 mol/l KCl from the deficient muscle extract displayed kinetic properties distinctly different from those of normal muscle and resembled in this respect the isoform from fetal tissue. The experiments presented suggest that disturbances in the mechanisms regulating an alternative splicing of the primary transcript of skeletal muscle AMP-deaminase gene might be the molecular basis of the defect.