Metabolic interaction between purine nucleotide cycle and oxypurine cycle during skeletal muscle contraction of different intensities: a biochemical reappraisal
A substrate cycle is a metabolic transformation in which a substrate A is phosphorylated to A−P at the expense of ATP (or another “high energy” compound), and A−P is converted back to A by a nucleotidase or a phosphatase. Many biochemists resisted the idea of such an ATP waste. Why a non-phosphorylated metabolite should be converted into a phosphorylated form, and converted back to its non-phosphorylated form through a “futile cycle”?
Aim of review
In this Review we aim at presenting our present knowledge on the biochemical features underlying the interrelation between the muscle purine nucleotide cycle and the oxypurine cycle, and on the metabolic responses of the two cycles to increasing intensities of muscle contraction.
Key scientific concepts of review
Nowadays it is widely accepted that the substrate cycles regulate many vital functions depending on the expense of large amounts of ATP, including skeletal muscle contraction, so that the expense of some extra ATP and “high energy” compounds, such as GTP and PRPP via substrate cycles, is not surprising. The Review emphasizes the strict metabolic interrelationship between the purine nucleotide cycle and the oxipurine cycle.
KeywordsTheoretical basis of substrate cycles The purine nucleotide cycle The oxypurine cycle The interaction between the purine nucleotide cycle and the oxypurine cycle The overall equation of the aerobic glycogen catabolism
Purine nucleotide cycle
Purine nucleoside phosphorylase
Glycolysis starting from glycogen
This work was supported by local funds of the University of Pisa. Authors are grateful to Prof. Umberto Mura for precious advice.
- Barsotti, C., Pesi, R., Felice, F., & Ipata, P. L. (2003). The purine nuclesoside cycle in cell-free extrats of rat brain: Evidence for the occurrence of an inosine and a guanosine cycle with distinct metabolic roles. Cellular and Molecular Life Sciences CMLS, 60(4), 786–793CrossRefPubMedGoogle Scholar
- Kammen, H. O., & Koo, R. (1969). Phosphopentomutase. Identification of two activities in rabbit tissues. Journal of Biological Chemistry, 244, 488–493.Google Scholar
- Lehninger, A., Nelson, D. L., & Cox, M. M. (1993). Futile cycles in carbohydrate metabolism consume ATP. In Principles of biochemistry (2nd ed.). (pp. 606–607). New York: Worth Publishers.Google Scholar
- Newsholme, E. A., & Leech, A. R. (1988). Substrate cycles. In Biochemistry for the medical sciences, Reprinted with corrections pp. 306–308. Great Britain: Wiley.Google Scholar
- Robergs, R. A., Ghiasvand, F., & Parker, F. (2004). Biochemistry of exercise induced metabolic acidosis. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 267, R502–R516.Google Scholar
- Stryer, L. (1995). Substrate cycles amplify metabolic signals and produce heat. In: Biochemistry (4th ed., p. 576). New York: Freeman and Company.Google Scholar
- Voet, D., Voet, J. G., & Pratt, C. W. (2013). Il ciclo del substrato regola finemente il flusso. In: Fondamenti di Biochimica (3rd Italian Edition based on the 4th American edition, pp. 528–529). Zanichelli Editore: Bologna.Google Scholar
- Zielinski, J., & Kusy, K. (2015). Pathways of purine metabolism: Effects of exercise and training in competitive athletes. Trends in Sport Sciences, 3, 103–215.Google Scholar