Phosphocreatine shuttle

Cellular adenine nucleotides are compartmentalized by their very low diffusibility (due to their size and charge) with pools in the mitochondria, at the myofibrils, SR, and other sites of energy utilization. CK is located at those sites. Phosphocreatine is much smaller and less charged, and therefore much more mobile in cells than ATP. ATP produced by substrate-level phosphorylation in glycolysis may be used to rephosphorylate creatine in the sarcoplasm  

Phosphocreatine shuttle. A myokinase (adenylate kinase) cascade between oxidative phosphorylation and creatine kinase (CK) has been postulated. A similar myofibrillary cascade may exist at the myofibrillar ATPase site. 

Supplementation with creatine has not been found to enhance aerobic work performance despite measurable increases in muscle creatine and phosphocreatine, suggesting that energy transfer in muscle cells is not normally limited by the total creatine concentration. However, ability to perform intermittent high-intensity work is enhanced, indicating that the energy storage function of PC is increased by creatine supplementation. 

Creatine kinase (also called creatine phosphokinase, or CPK) is a dimer of subunit molecular weight 40,000. The brain isozyme is a dimer of B subunits. In skeletal muscle, the principal form is a homodimer of M subunits. In cardiac muscle, 80-85% of the CK is MM, the balance is MB. These isozymes are electrophoretically distinct, as is mitochondrial CK. Depending on fiber type, 10-30% of CK activity is on the outer side of the inner mitochondrial membrane, 3—4% is at the M-lines, and the remainder is in 

Measurement of serum concentration of total CK and CK-2 (i.e., MB) have long been used to assess the extent of myocardial damage in suspected MI (Chapter 8). Measurement of LDH isozymes has been used similarly. In recent years, however, reliance on cardiac troponin assays has increased and use of CK and LDH assays will probably decrease. 

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Energy transport in the cytosol the creatine/phosphocreatine shuttle... 

In spermatozoa, the phosphocreatine shuttle is present to transfer energy from the mitochondria to the flagellum, which is essential for swimming of the sperm (Figure 9.21) (see also Chapter 19). 

Figure 9.20 The creatine/phosphocreatine shuttle between subsarcolemmal mitochondria and myosin ATPase in muscle. The distance between the mitochondria that reside just below the plasma membrane (sarcolemma) and the myofibrils in which the myosin ATPase results in contraction, is long in such muscles. The advantage of the position of these mitochondria is ready access to oxygen and fuel from blood. Such mitochondria are common in endurance athletes.

Figure 9.21 The creatine/phosphocreatine shuttle in spermatozoa. This shuttle may not be present in all sperm it will depend upon the distance between the mitochondria and the flagellum. Mitochondria are present in the midpiece just below the head. ATP is required for movement of the flagellum which enables the sperm to swim. Dynein ATPase is the specific motor ATPase, similar to myosin ATPase, that transfers energy from ATP to the flagellum. A deficiency of creatine may explain low sperm motility in some infertile men. CK - creatine kinase. Deficiences of enzymes in the pathway for synthesis of creatine are known to occur (see Appendix 8.3).

The midpiece contains the mitochondria which are wrapped around the proximal part of the flagellum. The beating of the flagellum, and hence the swimming of the sperm involves the motor protein known as dynein, which requires ATP hydrolysis. In some species, the diffusion of energy in the spermatozoa is increased by the presence of the creatine/phosphocreatine shuttle (Chapter 9) that is, phosphocreatine and creatine diffuse throughout the cytosol... 

Tombes, R.M. Shapiro, B.M. Enzyme termini of a phosphocreatine shuttle. Purification and characterization of two creatine kinase isozymes from sea urchin sperm. J. Biol. Chem., 262, 16011-16019 (1987)... 

Energy transfer between mitochondria and the myofibrillar ATPases is mediated by phosphocreatine (Chapter 17). The phosphocreatine shuttle is illustrated schematically in Figure 21-13. Synthesis of ATP in mitochondria is closely coupled to that of phosphocreatine. Since the reaction... 

In addition to the processes described above, there still remains one further process which, at least in some cells or tissues, is required prior to the utilisation of ATP in the cytosol that is, the transport of energy within the cytosol, via a shuttle. The transport of ATP out and ADP into the mitochondrion, via the translocase, results in a high ATP/ ADP concentration ratio in the cytosol. However, a high ratio means that the actual concentration of ADP in the cytosol is low, which could result in slow diffusion of ADP from a site of ATP utilisation back to the inner mitochondrial membrane. If sufficiently slow, it could limit the rate of ATP generation. To overcome this, a process exists that transports energy within the cytosol, not by diffusion of ATP and ADP, but by the diffusion of phosphocreatine and creatine, a process known as the phosphocreatine/creatine shuttle. The reactions involved in the shuttle in muscle help to explain the significance of the process. They are ... 

The concentration of phosphocreatine is usually greater than that of ATP and that of creatine greater than that of ADP so that these metabolites diffuse more rapidly. This is because diffusion depends upon the concentrations of participants and the concentration gradient the larger the gradient, the greater is the rate of diffusion. Consequently, the shuttle is important in cells where the distance between the sites of ATP utilisation and the mitochondria is large... 

Bessman, S. and F. Savabi, The role of phosphocreatine energy shuttle in exercise and muscle hypertrophy, in Creatine and Creatine Phosphate Scientific and Clinical Perspectives, M.A. Conway and J.F. Clark, Eds. Academic Press, San Diego, CA,... 

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