Inhibition of the mitochondrial tricarboxylate carrier by arginine-specific reagents.
The effect of arginine-specific reagents on the activity of the partially purified and reconstituted tricarboxylate carrier of the inner mitochondrial membrane has been studied. It has been found that 1,2-cyclohexanedione, 2,3-butanedione, phenylglyoxal and phenylglyoxal derivatives inhibit the reconstituted citrate/citrate exchange activity. The inhibitory potency of the phenylglyoxal derivatives increases with increasing hydrophilic character of the molecule. Citrate protects the tricarboxylate carrier against inactivation caused by the arginine-specific reagents. Other tricarboxylates, which are not substrates of the carrier, have no protective effect. The results indicate that at least one essential arginine residue is located at the substrate-binding site of the tricarboxylate carrier and that the vicinity of the essential arginine(s) has a hydrophilic character.
D000818:Animals; D001120:Arginine / Q000502:physiology; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D002951:Citrates / Q000378:metabolism / Q000494:pharmacology; D003512:Cyclohexanones / Q000494:pharmacology; D003931:Diacetyl / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008565:Membrane Proteins / Q000378:metabolism; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D010658:Phenylglyoxal / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats
D002352:Carrier Proteins; D002951:Citrates; D003512:Cyclohexanones; D008081:Liposomes; D008565:Membrane Proteins; C020723:citrate-binding transport protein; C018031:1,2-cyclohexanedione; D001120:Arginine; D003931:Diacetyl; D010658:Phenylglyoxal