Inhibition of the Oxidation of Glutamate and Isocitrate in Liver Mitochondria at a Specific NADP+-reducing Site
Abstract
The cation-complexing carboxylic-acid antibiotic X-537A, at concentrations far below that required for ionophorous activity, selectively inhibits the oxidation of glutamate and isocitrate by liver mitochondria in steady-state 3. The site of inhibition has been localized specifically at the reduction of NADP+. Glutamate and isocitrate dehydrogenases, the oxidation of NAD+-dependent substrates, pyridine nucleotide transhydrogenations, and the respiratory chain between NADH (or NADPH) and O2 are unaffected by the antibiotic X-537A. Kinetic evidence, i.e., competition between chlorotetracycline (a fluorescence probe for membrane-bound bivalent cation) and X-537A, indicates that the NADP+-reducing, antibiotic-sensitive site is most probably associated with the inner mitochondrial membrane.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- December 1973
- DOI:
- 10.1073/pnas.70.12.3450
- Bibcode:
- 1973PNAS...70.3450L