STUDIES ON THE EFFECTS OF AMMONIA ON THE MITOCHONDRIAL RESPIRATION AND ON THE LEVELS OF PYRIDINE NUCLEOTIDES IN MITOCHONDRIA

Abstract

Ammonia is well known to be an inhibitor of cytoplasmic respiration in mitochondria, but the mechanism of its inhibition is not known. It has been previously reported from our laboratory that ammonia is most inhibitory for the respiration of citrate or isocitrate, and it causes a decrease in pyridine nucleotides level in mitochondria. The present author has further investigated the problem in detail using oxygen analyser and it was found that ammonia affects on the respiration only when electron transporting system works fully by an addition of adenosine diphosphate of 2,4-dinitrophenol. Glutamate was found in a trace amount in the system with addition of ammonia. On the other hand, pyridine nucleotide level did not changed in a low concentration of ammonia, although the respiratory inhibition was significant. It is considered that a decrease in pyridine nucleotide level by ammonia would not cause the respiratory inhibition, but the former is led by the latter. NADH_2 oxidase which is activated by ammonia, was purified about 130 fold from pig liver mitochondria. The existence of nicotinamide mononucleotide and nicotinamide riboside oxidase and dehydrogenase in liver cells was discussed.