VOL. 3, No. 3, July 2006

I. Kalvinsh, et al. [2006] Med Hypotheses Res 3: 803-812.

Hypothetical gamma-Butyrobetaine Esterase-Dependent
Signal Transduction System: Possible Link to
Mildronate Action

Ivars Kalvinsh, Aleksandrs Gutcaits, Lida Bagdoniene, Danute
Labeikyte, Peteris Trapencieris and Nikolajs Sjakste*

Latvian Institute of Organic Synthesis, Aizkraukles Street 21, Riga LV1006, Latvia (I.K., A.
G., P.T.), Department of Biochemistry and Biophysics, Vilnius University, M. K. Čiurlionio
21, LT-2009 Vilnius, Lithuania (L.B., D.L.) and Faculty of Medicine, University of Latvia,
Sharlotes Street 1a, Riga LV 1001, Latvia (N.S.)

Abstract. The idea about existence of an electron transfer system outside the nervous
system arises from simple consideration that if the signal transfer from nerve fibres to organs
is of electric nature, a recurrent flow of electrons from effector cells to nervous system should
exist in order to form a closed electric circuit. Several lines of scientific considerations all
indicate that the gamma-butyrobetaine and gamma-butyrobetaine esters could perform this
function. The gamma-butyrobetaine esterase activity, a necessary prerequisite for the
existence of such a system, was detected in rat blood. Our recent results suggest that action
of the anti-ischemic drug mildronate could be mediated, in part, by the stimulation of the
gamma-butyrobetaine and gamma-butyrobetaine ester pathway and the production of the
nitric oxide as a secondary messenger.

*Address all correspondence to: Dr. Nikolajs Sjakste, Biochemistry Group,
Latvian Institute of Organic Synthesis, Aizkraukles Street 21, RIGA, LV1006, Latvia. Fax:
371-7553142. E-Mail:

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