physiology

The creatine / creatine phosphate system

By Fabrizio Felici

In resting conditions the ATP demands are modest but, when the fibers are stimulated to contract, this request increases immediately.

In a muscle cell, at rest, modest amounts of ATP are stored, but it cannot rely on it for long, once it has begun to contract. So to avoid the decrease in ATP supply, the muscle cell must increase its production rate in order to keep up with the increase in speed of use. The ATP that provides the energy needed for the contraction is produced in the muscle cells by phosphorylation at the substrate level and by oxidative phosphorylation. When energy consumption increases in a cell, there is a reduction in the concentration of ATP and an increase in that of ADP. These variations lead to an increase in the activity of the enzymes responsible for ATP formation, with the consequence that ATP is produced at a higher rate. Although this occurs as soon as the cell begins to contract, these reactions take a few seconds to reach the necessary speed. So to ensure the availability of the required ATP meanwhile, the muscles rely on a high-energy and immediately available phosphate reserve, creatine phosphate (CP), which transfers its phosphate group to ADP (which is always present) for form ATP. The resting cell contains an amount of creatine phosphate sufficient to provide an amount of ATP equal to 4-5 times that normally present, which allows the cell to maintain its activity, until the other reactions capable of producing come into play. ATP.

The reaction of creatine phosphate with ADP is catalyzed by the enzyme creatine kinase and is reversible:

When this reaction proceeds from left to right, it generates ATP and creatine; when it goes from right to left, it generates ADP and creatine phosphate. In the resting muscle cell, the reaction is in equilibrium, and for each creatine phosphate molecule that forms, another is converted to creatine. When muscle activity starts instead, the concentration of ATP decreases, that of ADP increases, and the reaction proceeds to the right for the law of mass action. As a result, a certain amount of ADP is transformed into ATP, which can be used in the cycle of cross bridges at the expense of creatine phosphate, which is consumed. Since the stocks of CP are limited, this reaction can produce ATP only for a short time, but sufficient for the other metabolic reactions that supply ATP to be activated in the meantime. When the muscle cell ends the contraction, the creatine phosphate supply is restored because the reduced ATP demand causes an increase in the ATP concentration and a decrease in the ADP, causing a shift of the reaction to the left, so that creatine phosphate is again synthesized from creatine. In this way the CP reserves are preserved due to a sudden increase in activity at a later time.

The restoration of creatine phosphate reserves in the rapid restoration phase

A series of experiments highlighted important indications in this regard. In one of these experiments a muscle tissue sample was taken by needle biopsy before the beginning of physical exercise and, subsequently, periodically throughout the restoration phase following the exhaustive maximal effort. The test was performed in two different ways:

  • Muscle with normal blood flow
  • Muscle with occluded blood flow

In the first case it was observed that after only 2 minutes about 85% of the CP had been restored, while at the 4th minute of restoration the percentage reached 90%, to arrive at the almost complete restoration of the initial value after about 8 minutes.

In the second case, on the other hand, with occluded blood flow, the resynthesis of creatine phosphate does not occur: this has led to the confirmation that the regeneration cycle takes place thanks to the restoration oxygen transported in the blood by hemoglobin.

CP recovery (%)

Time (min.)

85

2

90

4

100

8

Naturally the greater the depletion of creatine phosphate due to exercise and the greater the amount of oxygen required for its resynthesis.