Alessandro Protti*, Francesco Fortunato, Massimo Monti, Sarah Vecchio, Stefano Gatti, Giacomo P Comi, Rachele De Giuseppe and Luciano Gattinoni
Corresponding author: Alessandro Protti email@example.com
Critical Care 2012, 16:R75 doi:10.1186/cc11332
(2012-05-28 15:04) Other
metformin is a uncoupling agent causes uncoupling of oxidative phosphorylation; due
to an increase in permeability of the inner mitochondrial membrane, protons heat is
generated without atp, (not using ATP synthase ligated channels) reactions involving
NADH, FADH increase, H+'s used, generating heat. other uncoupling agents include Salicyates,
Alcohol, Dinitrophenol, and of course Metformin. , "SAD-M". Perhaps induced hypothermia
would be of benefit in cases with malignant hyperthermia.
(2012-05-14 14:10) Ministry of Social Affairs and Health
The authors of this study have to be congratulated for their elegant experiments and
reaching the correct conclusions.
The drug is, in fact, an inhibitor of the complex I in the mitochondrial respiratory
chain. This seems to be the main reason for the deleterious effects. Two other circumstances
may, however, contribute and aggravate it. D-lactate produced excessively from glucose
is slowly metabolized by the D-lactic acid oxidase prolonging the metabolic acidosis,
and acidotic excessive protons impair the the terminal cytochrome oxidase which is
essentially a proton pump to molecular oxygen.
Thus, metformin interferes with the oxidative phosphorylation at several stages.
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