Tributyltin (TBT) and dibutyltin (DBT) differently inhibit the mitochondrial Mg-ATPase activity in mussel digestive gland.
Tri-n-butyltin (TBT) has long been considered as the most toxic among organotins, especially to membrane systems. The partially dealkylated derivative di-n-butyltin (DBT) has up to now received poor attention and, whenever considered, shown to be less toxic than TBT except on the immune system. The present kinetic approach evidences that both TBT and DBT in vitro inhibit the Mg-ATPase in mussel digestive gland mitochondria by a different mechanism. DBT even displays a higher efficiency than TBT (IC(50)=0.32 μM for TBT vs. 0.19 μM for DBT) in inhibiting the enzyme hydrolytic activity. Differently from TBT which at high concentrations (>1 μM) apparently decreases the oligomycin-sensitivity of the Mg-ATPase, DBT at any concentration tested does not affect the oligomycin sensitivity. TBT probably binds to F(0), either in the form of free enzyme or of enzyme-substrate complex (Ki=K'i), acting as non-competitive inhibitor with respect to the ATP substrate. Conversely DBT, which acts as uncompetitive inhibitor of ATP and as competitive inhibitor of Mg(2+) cofactor, may bind strongly to F(1) subunit, thus preventing ATP hydrolysis. The Mg-ATPase inhibition by both organotins warns against a potential threat to crucial cell energy metabolism processes even after years from contamination and partial TBT debutylation.
Nesci
Salvatore
S
Department of Biochemistry G. Moruzzi, University of Bologna, Ozzano Emilia (BO), Italy.
Ventrella
Vittoria
V
Trombetti
Fabiana
F
Pirini
Maurizio
M
Borgatti
Anna Rosa
AR
Pagliarani
Alessandra
A
D000818:Animals; D055162:Biocatalysis; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors*; D004064:Digestive System / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D049878:Mytilus / Q000201:enzymology*; D009792:Oceans and Seas; D009840:Oligomycins / Q000494:pharmacology; D009947:Organotin Compounds / Q000633:toxicity*; D021122:Protein Subunits / Q000037:antagonists & inhibitors; D014220:Trialkyltin Compounds / Q000633:toxicity*; D014874:Water Pollutants, Chemical / Q000633:toxicity
D004791:Enzyme Inhibitors; D009840:Oligomycins; D009947:Organotin Compounds; D021122:Protein Subunits; D014220:Trialkyltin Compounds; D014874:Water Pollutants, Chemical; C056189:di-n-butyltin; C011559:tributyltin; D017301:Ca(2+) Mg(2+)-ATPase