Stabilization of NADH-dehydrogenase in mitochondria by guanosine phosphates and adenosine phosphates.

Abstract

It is known that one of the reasons, leading to the development of neuromuscular diseases, including Parkinson's disease, is damage of the mitochondrial NADH-dehydrogenase. Perhaps, it happens when NADH-dehydrogenase loses connection with its coenzyme--flavine mononucleotide (FMN) that occurs at various influences on the enzyme. Previously, we have developed a method, based on fluorescence spectroscopy, to monitor the rate of exit of FMN from isolated mitochondria to solution. Also, we obtained the data that this process is blocked by the enzyme substrate - NADH or by the product - NAD. Recently, we found that this process is strongly blocked by adenine analogs of NAD, contained phosphates: ATP, ADP, and AMP. Adenosine phosphates are able to stabilize the FMN molecule in NADH-dehydrogenase. Using fluorescence spectroscopy and photocolorimetry, we have tested also other natural purine compounds - cAMP, cGMP, GMP, GDP, GTP, IMP, inosine, guanine, and caffeine. It is found that such derivatives of guanine as GMP, GDP, and GTP can prevent the release of FMN into solution. Guanine, cGMP, cAMP and caffeine did not prevent this process. The obtained data allow understand the mechanism of mitochondrial diseases, involving damage of mitochondrial NADH-dehydrogenase, and may help in development of medicines for treatment of these diseases.