Heikki Savolainen, Dept. of Occup. Safety & Hlth., Tampere, Finland
22 February 2010
Dear Editor,
The interesting investigation shows that the biguanidine treatment interferes with the oxygen consumption (1). This is compatible with the fact that eg. metformin is an inhibitor of the functions of complex I in the mitochondrial respiratory chain (2).
The association with the lactic acidosis is less straightforward as the drug increases the D-lactic acid production (3) which is not subject to the same physiological regulation as L-lactate.
The increased formation of D-lactate is probably due to the increased methylglyoxal production from glucose.
The clearance of D-lactate is slow as it is oxidized by a high Km D-lactate oxidase in the mitochondria. Thus, the acidosis associated with it is of longer duration. It should be remembered that protons also hamper the mitonchondrial respiration so that this is an additional factor in the decrease in the oxygen consumption.
1 Protti et al. Critical Care 2010; 14: R22
2 Zmijewski et al. Am J Resp Crit Care Med 2008; 178: 168
Critical Care
Oxygen consumption and lactic acidosis
22 February 2010
Dear Editor,
The interesting investigation shows that the biguanidine treatment interferes with the oxygen consumption (1). This is compatible with the fact that eg. metformin is an inhibitor of the functions of complex I in the mitochondrial respiratory chain (2).
The association with the lactic acidosis is less straightforward as the drug increases the D-lactic acid production (3) which is not subject to the same physiological regulation as L-lactate.
The increased formation of D-lactate is probably due to the increased methylglyoxal production from glucose.
The clearance of D-lactate is slow as it is oxidized by a high Km D-lactate oxidase in the mitochondria. Thus, the acidosis associated with it is of longer duration. It should be remembered that protons also hamper the mitonchondrial respiration so that this is an additional factor in the decrease in the oxygen consumption.
1 Protti et al. Critical Care 2010; 14: R22
2 Zmijewski et al. Am J Resp Crit Care Med 2008; 178: 168
3 Talasniemi et L. Clin Biochem 2008; 41: 1099
Competing interests
None