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Active-site-directed inhibition of carnitine acetyltransferase.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 1983 Jan; Vol. 220 (1), pp. 193-9. - Publication Year :
- 1983
-
Abstract
- Methoxycarbonyl-CoA disulfide has been used as an active-site-directed inhibitor of carnitine acetyltransferase. Stoichiometric addition of methoxycarbonyl-CoA disulfide to carnitine acetyltransferase showed the modification of one sulfhydryl group with concomitant loss of about 80% enzyme activity. The rate of modification of this sulfhydryl group is an order of magnitude faster than that of the remaining sulfhydryl groups in the enzyme. Methoxycarbonyl-CoA disulfide inactivation is biphasic: k1 = 1.09 X 10(2) M-1 S-1, k2 = 1.1 X 10(1) M-1 S-1. This modification, Enz-SS-CoA is covalent; it can be reversed with either dithioerythritol or thiocholine. Acetyl-carnitine and acetyl-CoA protected the enzyme against methoxycarbonyl-CoA disulfide inactivation; however, carnitine did not. These results indicate the presence of a sulfhydryl group in carnitine acetyltransferase at the site of acetyl group transfer. Titration of carnitine acetyltransferase with nonspecific sulfhydryl reagents, DTNB, and rho-nitrophenoxycarbonyl methyl disulfide, revealed that four sulfhydryl groups were preferentially modified by these reagents. The results also show that seven other sulfhydryl groups are available for modification.
- Subjects :
- Binding Sites drug effects
Catalysis
Chemical Phenomena
Chemistry
Coenzyme A analogs & derivatives
Coenzyme A pharmacology
Disulfides pharmacology
Dithionitrobenzoic Acid pharmacology
Sulfhydryl Compounds
Acetyltransferases antagonists & inhibitors
Carnitine O-Acetyltransferase antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0003-9861
- Volume :
- 220
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 6830231
- Full Text :
- https://doi.org/10.1016/0003-9861(83)90400-9