文档介绍：Clinical Pharmacology and Toxicology or in children and adults with various
congenital or acquired metabolic diseases
of Dichloroacetate for which DCA is administered acutely or
chronicallv as a drui.
Peter W. Stacpoole,1,2 e N. Henderson,1 Zimeng Yan," Pharmacy'nm
and Maraaret 0. James3
From a medicinal standpoint, a principal
'Department of Medicine, 2Department of Biochemistry and Molecular site of action of DCA is the pyruvate dehy-
Biology, College of Medicine, 3Department of Medicinal Chemistry, drogenase (PDH) plex (PDC)
College of Pharmacy, University of Florida, Gainesville, Florida located in the mitochondrial inner mem-
brane. PDC catalyzes the reversible decar-
Dichloroacetate (DCA) is a xenobiotic of interest to both environmental toxicologists and boxylation of pyruvate to acetyl coenzyme
clinicians. The chemical is a product of water chlorination and of the metabolism of various drugs A (CoA), which is the rate-limiting step in
and industrial chemicals. Its accumulation in groundwater and at certain Superfund sites is the aerobic oxidation of glucose, pyruvate,
considered a potential health hazard. However, concern about DCA toxicity is predicated mainly and lactate in animal cells (Figure 1).
on data obtained in inbred rodent strains administered DCA at doses thousands of times higher PDC undergoes rapid posttranslational
than those to which