Creatine Kinase Activity and Cartilage Energy Metabolism: Creatine Kinase-creatine Phosphate Circuit Activity and Macromolecule Synthesis
نویسنده
چکیده
Earlier studies showed that there is significant creatine kinase activity in the epiphyseal growth cartilage, and there is stage-specific isoform expression. To further explore the role of this enzyme in cartilage development, we disrupted the creatine kinase creatine phosphate (CK-CP) circuit using the creatine analogue, cyclocreatine. We found that while cyclocreatine decreased creatine kinase activity, the drug did not alter the energy status of the cell, nor did it cause a significant loss in adenine nucleotides. However, we noted that the glycolytic pathway was very sensitive to the drug. At high concentrations, cyclocreatine reduced glucose entry into the cell by 100%, and there was almost complete suppression of lactate generation. Surprisingly, there were minimal changes in creatine phosphate concentrations. Although cyclocreatine did not influence mitochondrial energy generation, the possibility existed that it could modulate other maturation-dependent activities of the cell. Indeed, we found that there was decreased expression of type II and X collagen and osteopontin. These results suggest that the circuit is primarily concerned with the transduction of energy rather than the generation or storage of high energy equivalents. In this role, the circuit would serve to facilitate nucleotide transport from sites of generation to sites of utilization.
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تاریخ انتشار 2003