A molecular mechanism for modulating plasma Zn speciation by fatty acids.
Bottom Line: Albumin transports both fatty acids and zinc in plasma.The molecular mechanism for this effect is likely due to a large conformational change elicited by fatty acid binding to a high-affinity interdomain site that disrupts at least one Zn site.Albumin may be a molecular device to "translate" certain aspects of the organismal energy state into global zinc signals.
Affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.Show MeSH
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Mentions: To address the suspected impact of chain length,we conducted furthercompetition experiments using the C14 fatty acid myristate (MYR).The binding of MYR to albumin (Figure S7) closely matches that of the physiologically most abundant palmitateand stearate in terms of binding sites12 but is slightly weaker.23 Titrationswith Zn2+ in the presence of increasing amounts of MYR(Figure 5A) revealed that the stoichiometry(Figure 5B) and/or affinity of Zn2+ decrease dramatically in the presence of >1 molar equiv of MYR.Conversely, MYR titrations of the 1:1 Zn:BSA complex showed that theenergetics but not the stoichiometry of the binding reaction are affectedby Zn2+, as indicated by a decrease in affinity and exothermicity(Figure 5C; ΔΔH = 1.1 kcal/mol, average for five Myr). These observations can berationalized by assuming that the binding of MYR requires the dissociationof Zn2+ from BSA; since the binding reaction is exothermic(ΔH = −4.7 kcal/mol), this dissociationmust be endothermic, although the difference in experimental conditionsprecludes direct quantitative comparisons.
Affiliation: Department of Chemistry, University of Warwick, Coventry CV4 7AL, UK.