J. Biol. Chem., Vol. 265, Issue 16, 9214-9220, 06, 1990
Selective inactivation of peroxisomal and cytosolic 3-ketothiolase IB by 2-chloro-6-phenylhexanoate in intact hepatocytes
GB Sephton and JM Lowenstein
Graduate Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254-9110.
Rat liver mitochondria and cytosol contain two types of 3- ketothiolases,
namely 3-ketothiolases IA and IB, which cleave 3- ketoacyl-coenzyme A (CoA)
esters containing four or more carbons and 3- ketothiolases IIA and IIB,
which cleave 3-ketoacyl-CoA esters containing four carbons, i.e.
acetoacetyl-CoA (Aragon, J.J., and Lowenstein, J.M. (1983) J. Biol. Chem.
258, 4725-4733). We now report that rat liver peroxisomes also contain
3-ketothiolases IA and IB and show that incubation of hepatocytes with
2-chloro-6-phenylhexanoate causes the selective inactivation of peroxisomal
and cytosolic 3- ketothiolase IB, while mitochondrial 3-ketothiolases are
not appreciably affected. The basis of the selectivity of the inhibitor for
peroxisomal and cytosolic 3-ketothiolases can be accounted for in terms of
the specificities of the enzymes in the different pathways of beta-
oxidation. Evidence is presented that 2-chloro-6-phenylhexanoate is
metabolized to 2-chloro-3-keto-6-phenylhexanoyl-CoA, which then alkylates
3-ketothiolase and thereby inactivates the enzyme. Evidence is presented
which suggests that cytosolic 3-ketothiolases IA and IB are not artifacts
of homogenization and organelle preparation.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?