In vitro effect of caffeine on some aspects of nitrogen metabolism in isolated rat hepatocytes

Long-term exposure to high doses of caffeine affects several aspects of nitrogen metabolism, such as purine, pyrimidine and urea synthesis. However, little is known about the mechanisms of these changes and if they occur at shorter term. We have studied in isolated hepatocytes: 1) the in vitro effect of high doses of caffeine on amino acid levels, 2) the main destination of ammonia and carbon chains from amino acid catabolism, and 3) the cytosolic and mitochondrial redox states. We have found that, whereas it has a small effect on urea synthesis and on the levels of the cofactors and intermediates, it decreases the levels of several amino acids, the gluconeogenesis and the redox state. Our results suggest that a longer exposure to caffeine is necessary to affect the normal functions of some metabolic pathways.