Dichloroacetic acid (DCA) arises from the chlorination of drinking wat
er and the metabolism of trichloroethylene (TRI) and is used therapeut
ically. The toxicity of TRI exposure is dependent on metabolism, and D
CA has been proposed to be one contributor to this toxicity. Beyond th
e identification of some metabolites of DCA and some pharmacokinetic s
tudies, little is known about the tissue distribution and enzymology o
f DCA metabolism. We present data that indicate that DCA degradation o
ccurs primarily in the cytosol. Low molecular weight components of cyt
osol are required for the reaction, including nicotinamide cofactor an
d glutathione (GSH). GSH plays a role in the removal of DCA from cytos
ol, although not through transferase-mediated conjugation. In rat cyto
sol, the K-M is approximately 0.3 mM, and the apparent V-max approxima
tes 12 nmoles/min/mg cytosolic protein. These results set DCA apart fr
om other chlorinated compounds that are metabolized by the cytochrome
P450 enzyme family.