Disease relevance of alpha-Picolinic acid

• The growth of a solid tumor induced by im implantation of Ehrlich ascites tumor cells in inbred CBA/J mice was retarded by treatment with an iron chelator, picolinic acid (PLA) [1].
• Phenoxy and picolinic acid herbicides and small-intestinal adenocarcinoma in sheep [2].
• Selective toxicity induced by picolinic acid in simian virus 40-transformed cells in tissue culture [3].
• The effects of picolinic acid (PA) on the intramacrophagic growth of Mycobacterium avium were studied [4].
• The cholera toxin response is also increased about 7-fold in simian virus 40-transformed NRK cells and Moloney sarcoma virus-transformed NRK cells treated with picolinic acid [5].

High impact information on alpha-Picolinic acid

• We have isolated mutants of SV40-transformed BALB/3T3 cells adapted to grow in picolinic acid [6].
• Functional studies using a tk promoter-CAT reporter gene plasmid demonstrated that the iNOS-HRE was sufficient to confer inducibility by picolinic acid but not by IFN-gamma or LPS [7].
• Deletion or mutation of the iNOS promoter region from -227 to -209, containing a sequence homology to a hypoxia-responsive enhancer (iNOS-HRE), decreased picolinic acid- but not LPS-induced CAT activity by more than 70% [7].
• Furthermore, based on flow cytometry, Arabidopsis thaliana plants overexpressing Arabidopsis HXK1 and HXK2, both of which are predominantly associated with mitochondria, exhibited enhanced resistance to H(2)O(2)- and alpha-picolinic acid-induced PCD [8].
• The resulting 38C2-5-Cu conjugate was an active catalyst for the hydrolysis of the coordinating picolinate ester 11, following Michaelis-Menten kinetics [kcat(11) = 2.3 min(-1) and Km(11) 2.2 mM] with a rate enhancement [kcat(11)k(uncat)(11)] of 2.1 x 10(5) [9].

Chemical compound and disease context of alpha-Picolinic acid

• The bacteria could be protected from this enhanced toxicity by the addition of free radical scavengers (ethanol, ascorbate, hydrogen peroxide, mannitol, glucose, EDTA, picolinic acid), indicating that the lethal reactions were extracellular in origin [10].
• Conversion from arenes having a benzene ring to those having a picolinic acid by simple growing cell reactions using Escherichia coli that expressed the six bacterial genes involved in biphenyl catabolism [11].
• Activity of picolinic acid in combination with the antiprotozoal drug quinacrine against Mycobacterium avium complex [12].
• Flavopiridol inhibits vascular endothelial growth factor production induced by hypoxia or picolinic acid in human neuroblastoma [13].
• Antimicrobial activity of picolinic acid against extracellular and intracellular Mycobacterium avium complex and its combined activity with clarithromycin, rifampicin and fluoroquinolones [14].

Biological context of alpha-Picolinic acid

• Transient transfection assays showed that the full-length iNOS promoter in the murine macrophage cell line ANA-1 was activated by the synergistic interaction between IFN-gamma and picolinic acid [7].
• When cultured normal and SV40-transformed normal rat kidney and BALB/3T3 cells were exposed to picolinic acid, cell proliferation ceases [3].
• Chromium(III) picolinate produces chromosome damage in Chinese hamster ovary cells [15].
• Macrophage control of mycobacterial growth induced by picolinic acid is dependent on host cell apoptosis [4].
• Cells with null alleles in both the relA and spoT genes are found no longer to accumulate ppGpp after glucose exhaustion or after chelation of manganese ions by picolinic acid addition; the inability to form ppGpp is reversed by a minimal spoT gene on a multicopy plasmid [16].

Anatomical context of alpha-Picolinic acid

• We now report that IL-4 also inhibited IFN-gamma plus picolinic acid-induced cytotoxicity in ANA-1 macrophages [17].
• Addition of picolinic acid to resting T-lymphocytes in the absence of mitogen induces a marked decrease of their ferritin content, but not the appearance of transferrin receptors [18].
• Here, we report that trivalent chromium in the chloride (CrCl3) or picolinate (CrPic) salt forms mobilize the glucose transporter, GLUT4, to the plasma membrane in 3T3-L1 adipocytes [19].
• Picolinic acid (PA) was measured by high pressure liquid chromatography in human milk and other fluids and tissues [20].
• Picolinic acid in milk, pancreatic juice, and intestine: inadequate for role in zinc absorption [20].

Associations of alpha-Picolinic acid with other chemical compounds

• In this study we investigated the effects of picolinic acid, a catabolite of L-tryptophan, on the production of L-arginine-derived reactive nitrogen intermediates in the murine macrophage cell line ANA-1 [21].
• Therefore, picolinic acid may affect NO2- production via both TNF-alpha-dependent and TNF-alpha-independent pathways [21].
• [2-14C]Acetate is readily incorporated into quinolinate in the in vitro system but only slightly into homarine and not at all into picolinate [22].
• The Kd values for both picolinate and anthranilate were determined from pH 5.4 to 9 [23].
• The synthetic activator of P-enolpyruvate carboxykinase, 3-aminopicolinic acid, as well as other picolinic acid derivatives, is capable of withdrawing Fe2+ associated with the mitochondrial fraction; after incubation with mitochondria, 3-aminopicolinate will activate phosphoenolpyruvate carboxykinase in the absence of exogenous metal [24].
• The inclusion of two picolinate groups on a triazacyclononane framework affords the mono-aquo gadolinium complex [Gd(bpatcn)(H(2)O)] with favourable electron-relaxation properties (tau(eff)(S0)=125 ps) [25].

Gene context of alpha-Picolinic acid

• LPS and picolinic acid caused a significant decrease of IDO activity in IFN-gamma-activated MT2 cells [26].
• Picolinic acid- or desferrioxamine-inducible autocrine activation of macrophages engineered to produce IFNgamma: an approach for gene therapy [27].
• Antagonistic effect of picolinic acid and interferon-gamma on macrophage inflammatory protein-1alpha/beta production [28].
• LPS and picolinic acid, two costimulatory agents that up-regulate inducible NOS in activated cells, regulated IDO induction differently in the two cell lines [26].
• Some of the pyridine-2-carboxylic acid derivatives (compound 2 and 3) had selective inhibition of the growth of map2 deletion yeast and weak inhibition on wild-type yeast growth, while no inhibition on map1 deletion yeast [29].

Analytical, diagnostic and therapeutic context of alpha-Picolinic acid

• Electrophoretic mobility shift assays confirmed that picolinic acid alone induced a specific binding activity to the iNOS-HRE [7].
• In this report we demonstrate that a family of inhibitors with a core structure of pyridine-2-carboxylic acid previously developed for the bacterial and yeast MetAP1 is also specific for human MetAP1 (HsMetAP1), as confirmed by both enzymatic assay and high-resolution x-ray crystallography [30].
• In contrast, a major increase of NOS mRNA expression was observed after treatment with IFN-gamma plus picolinic acid [31].
• Northern blot analysis revealed that, in MT2 macrophages, NOS inhibitors increased the levels of IDO mRNA, while a reduction was observed with picolinic acid [26].
• A high resolution HPLC method, capable of separating picolinate, nicotinate and isonicotinate, was developed and used in product identification [32].

References