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.