Tullson P C, Rush J W, Wieringa B, Terjung R L
Department of Physiology, State University of New York, Health Science Center at Syracuse 13210, USA.
Am J Physiol. 1998 May;274(5):C1411-6. doi: 10.1152/ajpcell.1998.274.5.C1411.
Alterations in the competency of the creatine kinase system elicit numerous structural and metabolic compensations, including changes in purine nucleotide metabolism. We evaluated molecular and kinetic changes in AMP deaminase from skeletal muscles of mice deficient in either cytosolic creatine kinase alone (M-CK-/-) or also deficient in mitochondrial creatine kinase (CK-/-) compared with wild type. We found that predominantly fast-twitch muscle, but not slow-twitch muscle, from both M-CK-/- and CK-/- mice had much lower AMP deaminase; the quantity of AMP deaminase detected by Western blot was correspondingly lower, whereas AMP deaminase-1 (AMPD1) gene expression was unchanged. Kinetic analysis of AMP deaminase from mixed muscle revealed negative cooperativity that was significantly greater in creatine kinase deficiencies. Treatment of AMP deaminase with acid phosphatase abolished negative cooperative behavior, indicating that a phosphorylation-dephosphorylation cycle may be important in the regulation of AMP deaminase.
肌酸激酶系统活性的改变引发了许多结构和代谢补偿，包括嘌呤核苷酸代谢的变化。我们评估了单独缺乏胞质肌酸激酶（M-CK-/-）或同时缺乏线粒体肌酸激酶（CK-/-）的小鼠骨骼肌中AMP脱氨酶的分子和动力学变化，并与野生型小鼠进行比较。我们发现，M-CK-/-和CK-/-小鼠的主要快肌而非慢肌中，AMP脱氨酶含量低得多；通过蛋白质印迹法检测到的AMP脱氨酶量相应较低，而AMP脱氨酶-1（AMPD1）基因表达未发生变化。对混合肌肉中AMP脱氨酶的动力学分析显示存在负协同性，在肌酸激酶缺乏时这种负协同性显著增强。用酸性磷酸酶处理AMP脱氨酶消除了负协同行为，这表明磷酸化-去磷酸化循环可能在AMP脱氨酶的调节中起重要作用。
