Heikki Savolainen, Dept. of Occup.Safety & Hlth., Tampere, Finland
25 May 2011
Dear Editor,
The ideas raised in the review (1) are excellent. It is now clear that L-lactate, for example, has also important regulatory roles in addition to its fuel characteristics (2).
However, many diketones, e.g. methylglyoxal (3)and diketohexane (4), toxic. The former is a metabolite of glucose and the second is derived from n-hexane, an industrial solvent. The compounds can form so-called Schiff bases with the free amino groups in the polypeptides rendering them nonfunctional or directly harmful.
Lastly, the end metabolite of methylglyoxal is D-lactate which cannot be metabolized as well as the physiological L form. However, it is taken up by the same monocarboxylate transporters as L-lactate thus accumulating in the cells. While using the ketone treatment it might be necessary to control the excretion of D-lactate (3) to avoid the toxicity associated with it.
1 White H, Venkatesh B. Critical review. Ketones and brain injury. Crit Care 2011, 15: 219
2 Rinholm JE, Hamilton NB, Kessaris N, et al. Regulation of oligodendrocyte development and myelination by glucose and lactate. J Neurosci 2011, 31: 538.
3 Talasniemi JP, Pennanen S, Savolainen H, et al. Assay of D-lactate in diabetic plasma and urine. Clin Biochem 2008, 41: 1099.
4 Savolainen H. Neurotoxicity of industrial chemicals and contaminants. Aspects of biochemical mechanisms and effects. Arch Toxicol 1982, suppl 5: 71
Neurotoxicity of ketones
25 May 2011
Dear Editor,
The ideas raised in the review (1) are excellent. It is now clear that L-lactate, for example, has also important regulatory roles in addition to its fuel characteristics (2).
However, many diketones, e.g. methylglyoxal (3)and diketohexane (4), toxic. The former is a metabolite of glucose and the second is derived from n-hexane, an industrial solvent. The compounds can form so-called Schiff bases with the free amino groups in the polypeptides rendering them nonfunctional or directly harmful.
Lastly, the end metabolite of methylglyoxal is D-lactate which cannot be metabolized as well as the physiological L form. However, it is taken up by the same monocarboxylate transporters as L-lactate thus accumulating in the cells. While using the ketone treatment it might be necessary to control the excretion of D-lactate (3) to avoid the toxicity associated with it.
1 White H, Venkatesh B. Critical review. Ketones and brain injury. Crit Care 2011, 15: 219
2 Rinholm JE, Hamilton NB, Kessaris N, et al. Regulation of oligodendrocyte development and myelination by glucose and lactate. J Neurosci 2011, 31: 538.
3 Talasniemi JP, Pennanen S, Savolainen H, et al. Assay of D-lactate in diabetic plasma and urine. Clin Biochem 2008, 41: 1099.
4 Savolainen H. Neurotoxicity of industrial chemicals and contaminants. Aspects of biochemical mechanisms and effects. Arch Toxicol 1982, suppl 5: 71
Competing interests
None