Metabolic effects of tricarboxylic acid cycle intermediates
Heikki Savolainen, Dept. of Occup. Safety & Hlth, Tampere, Finland
16 November 2005
The authors correctly stress the importance of lactate in acidosis but it should be remembered that succinate and fumarate have important metabolic roles as well. Succinate inhibits the prolyl hydroxylation of Hypoxia Inducible Factor -1 (HIF-1) in the proteasome pathway (1) thereby allowing the upregulation of hypoxia responsive elements (HRE). This could complicate the treatment while it also offers therapy options.
Critical Care
Metabolic effects of tricarboxylic acid cycle intermediates
16 November 2005
The authors correctly stress the importance of lactate in acidosis but it should be remembered that succinate and fumarate have important metabolic roles as well. Succinate inhibits the prolyl hydroxylation of Hypoxia Inducible Factor -1 (HIF-1) in the proteasome pathway (1) thereby allowing the upregulation of hypoxia responsive elements (HRE). This could complicate the treatment while it also offers therapy options.
1. Brière et al. Hum Mol Genet 14: 3263-9 (2005)
Competing interests
None declared