Because
creatine and
creatine phosphate are irreversibly converted to
creatinine, there is a continuous need for their replacement. This occurs by means of diet and de novo synthesis. Dietary
creatine is provided in animal products and can amount to about half of the required amount. Synthesis provides the remainder.
Creatine synthesis is a major component of
arginine metabolism, amounting to more than 20% of the dietary intake of this
amino acid.
Creatine metabolism is of importance to patients with
urea cycle disorders in two ways, both related to
arginine levels. In patients with
arginase deficiency, markedly elevated
arginine levels may result in higher concentrations of
guanidinoacetate and higher rates of
creatine synthesis. This is of concern because it is thought that elevated levels of
guanidinoacetate may exert neurotoxic effects. In the case of the other
urea cycle disorders,
arginine levels are markedly decreased unless the patients are supplemented with this
amino acid. Decreased levels of
arginine may result in decreased rates of
creatine synthesis. This may be compounded by the fact that such patients, maintained on
low protein diets, will also have lower dietary
creatine intakes. There is some evidence that this may decrease brain
creatine levels which may contribute to the neurological symptoms exhibited by these patients. It is clear that patients with
urea cycle disorders also have altered
creatine metabolism. Whether this contributes in a significant way to their neurological symptoms remains an open question.