Functional study on muscle nucleotide metabolism and AMP-activated protein kinase

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Adenine nucleotide metabolism has many functions including maintenance of ATP, regulation of DNA or RNA synthesis and production of cAMP or adenosine. AMPD, which catalyzes AMP to IMP, is thought to play an important role in this metabolism, though detailed function of AMPD in vivo has not been well understood. In this study, we studied gene knock-out mice for each AMPD gene or combined AMPD genes. First, we investigated those model mice for skeletal muscle function, since we successfully established skeletal muscle AMPD deficiency as seen in patients with myoadenylate deaminase deficiency. In skeletal muscle, AMPD deficiency did not cause dramatic changes in ATP/AMP ratio or AMPK phophorylation status. However, AMPD2 gene defect caused dramatic changes of glucose and lipid metabolism in liver through changes of AMPK phosphorylation status. These studies revealed the functional relevance of AMPD in mabolism and further studies are awaited.