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- Title
Effects of heavy metal cations on the mitochondrial ornithine/citrulline transporter reconstituted in liposomes.
- Authors
Tonazzi, Annamaria; Indiveri, Cesare
- Abstract
The effect of heavy metal cations on the mitochondrial ornithine/citrulline transporter was tested in proteoliposomes reconstituted with the protein purified from rat liver. The transport activity was measured as [H]ornithine uptake in proteoliposomes containing internal ornithine (ornithine/ornithine antiport mode) or as [H]ornithine efflux in the absence of external substrate (ornithine/H transport mode). 0.1 mM Cu, Pb, Hg, Cd and Zn strongly inhibited (more than 85%) the antiport; whereas Mn, Co and Ni inhibited less efficiently (25, 47 and 69%, respectively). The IC values of the transporter for the different metal ions ranged from 0.71 to 350 μM. Co and Ni also inhibited the [H]ornithine efflux whereas Cu, Pb, Hg, Cd and Zn stimulated the [H]ornithine efflux. The stimulation of the [H]ornithine efflux by Cu and Cd (as well as by Pb, Hg and Zn) was not prevented by NEM and was reversed by DTE. These features indicated that the inhibition of the antiport was due to the interaction of the Cu, Pb, Hg, Cd and Zn with a population of SH groups, of the transporter, responsible for the inhibition of the physiological function; whereas the stimulation of [H]ornithine efflux was due to the induction of a pore-like function of the transporter caused by interaction of cations with a different population of SH groups. Differently, the inhibition of the ornithine transporter by Ni, Co or Mn was caused by interaction with the substrate binding site, as indicated by the competitive or mixed inhibition.
- Subjects
CATIONS; HEAVY metals; ORNITHINE; DIAMINO amino acids; LIPOSOMES; METAL ions
- Publication
BioMetals, 2011, Vol 24, Issue 6, p1205
- ISSN
0966-0844
- Publication type
Article
- DOI
10.1007/s10534-011-9479-5