An In Vitro Study of the Effect of Picolinic Acid on Metal Translocation across Lipid Bilayers

Abstract

The effect of picolinic acid (pyridine-2-carboxylic acid) on the efflux of divalent metal ions from multilamellar liposomes was examined to determine the possible specificity and mechanism for its reported beneficial effects on the intestinal absorption and systemic metabolism of zinc. Extraliposomal picolinic acid increased the efflux of Zn, Cu, Co, Mn, Ni, Cd, Pb, Fe(II) and Ca from the vesicles. However, when picolinic acid was trapped with Co, Cu and Zn within the liposomes, the loss of metals was reduced. In a partition study, picolinic acid increased the aqueous solubility of Zn, Cu, Co and Cd at alkaline pH, but did not transfer the metal to an organic bulk phase of chloroform. It is proposed that picolinic acid does not act as an ionophore and that any effect it may have on zinc metabolism is dependent upon its unselective chelating properties, which may also lead to altered dietary and systemic compartmentation of other divalent cations.

Kynurenine pathway metabolism in human blood–brain–barrier cells: implications for immune tolerance & neurotoxicity

“…PIC is an unselective metal ion chelator (Aggett et al. 1989) and activates macrophages via induction of macrophage inhibitory protein (MIP)‐1α and MIP‐1β (Bosco et al.…”

“…PIC is an unselective metal ion chelator (Aggett et al 1989) and activates macrophages via induction of macrophage inhibitory protein (MIP)-1a and MIP-1b (Bosco et al 2000), which is potentiated by simultaneous IFN-c treatment (Pais and Appelberg 2000). It possesses both extracellular and intramacrophage anti-microbial activity against Mycobacterium avium (Cai et al 2006;Shimizu and Tomioka 2006), Candida albicans (Abe et al 2004) as well as antiviral/apoptotic activity against HIV-1-and Herpes simplex virus-2-infected cells (Fernandez-Pol et al 2001).…”

Kynurenines with Neuroactive and Redox Properties: Relevance to Aging and Brain Diseases

“…Later, Suzuki and coworkers described that PIC was also able to chelate other bivalent metals including Ni 2+ , Zn 2+ , Cd 2+ , Pb 2+ , and Cu 2+ [136]. Therefore, picolinate is an unselective metal ion chelator [137] and also activates macrophages via induction of macrophage inhibitory protein- (MIP-) 1 α and MIP-1 β , which is potentiated by simultaneous IFN- γ treatment [138]. It also possesses both extracellular and intramacrophage antimicrobial activity against Mycobacterium avium [139] and Candida albicans [140] and antiviral/apoptotic activity against HVI-1 and Herpes simplex virus-2-infected cells [141].…”

Changing the Face of Kynurenines and Neurotoxicity: Therapeutic Considerations

“…PIC is a non-selective metal ion chelating agent [ 68 ], induces morphological changes in the rat hippocampus, substantia nigra and striatum when administered intraperitoneally [ 69 ] and has a macrophage induction activity [ 70 ]. PIC is able to prevent QUIN-induced neurotoxicity when injected into the nucleus basalis magnocellularis of the rat [ 71 ], and it is able to modulate kainate-induced glutamate release from the striatum [ 72 ].…”