Fasting-induced inhibition of collagen biosynthesis in rat skin. A possible role for phosphoenolpyruvate in this process.

Fasting is accompanied by a decrease in collagen biosynthesis. The mechanism of this phenomenon involves inhibition of prolidase activity, an enzyme that plays a key role in upregulation of collagen metabolism. The mechanism of fasting-induced inhibition of prolidase activity is not known. Phosphoenolpyruvate (PEP) is known as a strong inhibitor of prolidase activity. It exerts this effect by inhibition of the enzyme phosphorylation. Unphosphorylated prolidase is inactive. One may expect that fasting-associated increase in posphoenolpyruvate content in animal tissues may be a factor which inactivates prolidase and makes it inactive in collagen biosynthesis. We measured the levels of phosphoenolpyruvate, pyruvate, and pyruvate kinase in the skin of control and fasted rats and correlated these parameters with prolidase expression, prolidase activity and collagen biosynthesis in this tissue. Significant increase of PEP concentration (about 30%) was found in the skin of fasted rats. In the same time prolidase activity and collagen biosynthesis decreased by about 50% and 30%, respectively, compared to controls. It is known that phosphoenolpyruvate is converted to pyruvate by the action of pyruvate kinase. Since fasting significantly decreases the activity of this enzyme, one may suggest that the accumulation of PEP is caused by a reduced utilisation of this metabolite. As demonstrated by Western immunoblot analysis the decrease in prolidase activity was not accompanied by a decrease in the amount of the enzyme protein. Instead, a decrease in the enzyme phosphorylation was observed. The reduction in phosphorylation seems to be responsible for the decrease in prolidase activity. These data suggest that fasting-evoked accumulation of PEP reduces the activity of prolidase, providing a mechanism for inhibition of collagen biosynthesis in the skin.