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Peter W. Stacpoole, Douglas S. Kerr, Carie Barnes, S. Terri Bunch, Paul R. Carney, Eileen M. Fennell, Natalia M. Felitsyn, Robin L. Gilmore, Melvin Greer, George N. Henderson, Alan D. Hutson, Richard E. Neiberger, Ralph G. O'Brien, Leigh Ann Perkins, Ronald G. Quisling, Albert L. Shroads, Jonathan J. Shuster, Janet H. Silverstein, Douglas W. Theriaque, and Edward Valenstein
Controlled Clinical Trial of Dichloroacetate for Treatment of Congenital Lactic Acidosis in Children
Pediatrics 2006; 117: 1519-1531 [Abstract] [Full text] [PDF]
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[Read eLetters] Lactate in acidosis
Heikki Savolainen   (5 May 2006)

Lactate in acidosis 5 May 2006
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Heikki Savolainen,
Professor
Dept. of Occup. Safety & Hlth, Tampere, Finland

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Re: Lactate in acidosis

heikki.savolainen{at}stm.fi Heikki Savolainen

The carefully conducted study (1) shows that enhanced clearance of circulating lactate is not associated with the improvement of the clinical status of patients. This may be caused by the circumstance that protons are more important to the outcome (2) than the anions.

Protons and are needed and consumed by the mitochondrial respiratory chain (3). It is linked to the tricarboxylic acid cycle by the succinate dehydrogenase. In case of the chain malfunction, the cycle intermediates begin to pile up. Succinate and fumarate (4) have important regulatory roles as they e.g. allow upregulation of hypoxia responsive genes controlled by the hypoxia inducible factor (HIF, ref. 5).

Control of acidosis and tricarcoxylic acid intermediates are thus equally important.

1.Stacpoole Pw, Kerr DS, Barnes C, et al. Controlled trial of dichloroacetate for treatment of congenital lactic acidosis in children. Pediatrics 2006; 117: 1519-1531.

2.Liesivuori J, Savolainen H. methanol and formic acid toxicity: Biochemical mechanisms. Pharmacol Toxicol 1991; 69: 157-163.

3. Hochachka PW, Mommsen TP. Protons and anaerobiosis. Science 1983; 219: 1391-1397.

4. Anderson NL, Wang Y, Blatnik M, et al. S-(2-succinyl)cysteine: A novel chemical modification of tissue proteins by a Krebs cycle intermediate. Arch Biochem Biophys 2006; in press.

5. Brière JJ, Favier J, Benit P, et al. Mitochondrial succinate is instrumental for HIF 1 alpha nuclear translocation in SDHA-mutant fibroblasts under normoxic conditions. Hum Mol Genet 2005; 14: 3263-3269.

Conflict of Interest:

None declared