Picolinic Acid Concentrations Research Articles

Central levels of tryptophan metabolites in subjects with bipolar disorder

The kynurenine pathway of tryptophan degradation produces several neuroactive metabolites such as kynurenic acid (KYNA), quinolinic acid (QUIN), and picolinic acid (PIC) thought to be involved in the pathophysiology of psychosis, major depression, and suicidal behavior. Here, we analyzed cerebrospinal fluid (CSF) concentrations of tryptophan, kynurenine, KYNA, QUIN, and PIC utilizing ultra-performance liquid chromatography – tandem mass spectrometry system (UPLC-MS/MS) in persons with bipolar disorder (n = 101) and healthy controls (n = 80) to investigate if the metabolites correlated with depressive symptoms or to the history of suicidal behavior. Furthermore, we analyzed if genetic variants of the enzyme amino-β-carboxymuconate-semialdehyde-decarboxylase (ACMSD) were associated with the CSF concentrations of PIC and QUIN. We found that CSF KYNA and PIC concentrations, as well as the kynurenine/tryptophan ratio were increased in bipolar disorder compared with controls. CSF PIC concentrations were lower in subjects with a history of suicidal behavior than those without, supporting the hypothesis that low CSF PIC is a marker of vulnerability for suicidality. Bipolar subjects taking antidepressants had higher CSF concentrations of kynurenine and KYNA than subjects not given these medications. A negative association was found between a genetic variant of ACMSD and the ratio of PIC/QUIN, indicating that a polymorphism in ACMSD is associated with excess of QUIN formation at the expense of PIC. The present results confirm that the kynurenine pathway is activated in bipolar disorder, and suggest that shifting the activity of the kynurenine pathway away from QUIN production towards a production of KYNA and PIC might be a beneficial therapeutic strategy.

Extraction Equilibria of Picolinic Acid with Trialkylamine/n-Octanol

The extraction equilibrium of picolinic acid using trialkylamine (N235) dissolved in n-octanol at 298 ± 0.5 K has been studied. The factors that affected distribution coefficients (D), such as aqueous equilibrium pH (pHeq), N235 concentration, and diluents, were investigated. As diluents, n-octanol showed higher D values than those of tetrachloromethane and kerosene. The maximum D values appeared at a N235 concentration of 0.4218 mol·L–1, which were in agreement with the results of the apparent alkalinity of N235/n-octanol. The D values were also observed with peak values at pHeq in the range of 4.5–6.0. In addition, D decreased with the increase of the initial picolinic acid concentration. Fourier transform infrared spectrometry confirmed that pHeq had no influence on the complexes’ structure and the extraction reaction belonged to the proton-transfer process. The expression of D was proposed based on the mass action law with reasonable assumptions, and the model parameters were calculated by fitting the experimental data. The D values obtained by the model were in good agreement with the experimental ones.

Kinetics and mechanism of the reaction between chromium(III) and picolinic acid in weak acidic aqueous solution

The interaction between chromium(III) and picolinic acid in weak acid aqueous solution was studied, resulting in the formation of a complex upon substitution of water molecules in the chromium(III) coordination sphere. Experimental results show that the reaction takes place in multiple steps. The first step is the formation of an ion pair, the second step (two consecutive steps) is the slow one corresponding to substitution of the first water molecule from the chromium aqueous complex coordination sphere by a picolinic acid molecule via oxygen atom of the carboxylic acid group and substitution of the second water molecule via nitrogen of the pyridine ring forming an 1:1 complex. Both consecutive steps were independent of chromium concentration. The rate constants of the 1st and 2nd consecutive steps were increased by increasing picolinic acid concentration. The corresponding activation parameters are ∆H 1 * = 28.4 ± 4 kJ mol−1, ∆S 1 * = −202 ± 26 J K−1 mol−1, ∆H 2 * = 39.6 ± 5 kJ mol−1, and ∆S 2 * = −175 ± 19 J K−1 mol−1. The third step is fast, corresponding to formation of the final complex [Cr(pic)3]. The logarithms of the formation constants of 1:1 and 1:3 complexes were found to be 1.724 and 4.274, respectively.

Age and circadian influences on picolinic acid concentrations in human cerebrospinal fluid

It has been suggested that picolinic acid (PIC), an endogenous metabolite of l-tryptophan, possesses neuro-protective and anti-proliferative effects within the CNS. However, the literature surrounding PIC is limited, and its exact endogenous function is not known. Picolinic acid is produced via the kynurenine pathway which has been implicated in the pathogenesis of a range of neuro-inflammatory diseases. Although not extensively studied, there have been reports of altered PIC production alongside other kynurenine metabolites in inflammatory disorders. In order to investigate whether PIC concentrations are altered with disease in the CNS, we analysed PIC levels in the CSF of 241 patients who underwent lumbar puncture as part of their standard clinical evaluation. In patients with no apparent CNS disease, CSF PIC levels were 10-fold higher in samples taken between 20:00 and 16:00 h compared with those collected between 04:00 and 12:00 h. This result suggests a diurnal variation in PIC synthesis within the CNS. In addition, we observed a direct correlation between a patient's age and their PIC concentration. No significant correlations were observed between CSF PIC levels and any specific disease state.

Mechanism of copper electrodeposition in the presence of picolinic acid

The influence of picolinic acid (PA) on copper deposition from a slightly acidic sodium sulphate electrolyte has been studied over a wide range of concentration and pH by cyclic voltammetry. The mechanism by which the copper electrodeposition process in the presence of PA takes place, depends on the chemistry and electrochemistry characteristics of the additive. Depending on the PA concentration and pH of the solution, five different cathodic current peaks are obtained, which are assigned to different steps involving copper deposition from free-Cu 2+ ions and [Cu(PA) n ] 2+ complex species as well as H + ions electroeduction. Fine-grained, highly adherent and bright copper deposits were obtained.

ECNI GC-MS analysis of picolinic and quinolinic acids and their amides in human plasma, CSF, and brain tissue.

To study the complex inter-relationships between inflammatory and apoptotic responses and the kynurenine pathway, we have utilized electron-capture negative ion mass spectrometry to develop trace analyses to concurrently quantify nicotinic acid (NIC), picolinic acid (PIC) and quinolinic acid (QUIN) in biological samples. We have shown that NIC and its amide nicotinamide (NAM) can be separately quantified by analyzing samples pre- and post-acid hydrolysis. We have now examined human plasma, CSF and brain tissue samples for the presence of putative picolinamide (PAM) and quinolinamide (QAM) by comparing PIC and QUIN concentrations pre- and post- gas phase hydrolysis. We report for the first time that, with respect to the free acids, relatively high concentrations of the amides (or, at least, hydrolysable precursors of the acids) are present in plasma and brain with marked relative increases in CSF. In normal control subjects (n=22) pre-hydrolysis plasma levels (+/- sem) of PIC and QUIN were 0.299 +/- 0.034 and 0.47 +/- 0.047 micromol/L respectively. Following hydrolysis the concentrations rose more than 4-fold to 1.33 +/- 0.115 and 2.2 +/- 0.27 micromol/L respectively. In CSF samples from patients with no sign of brain injury or pathology (n=10) pre-hydrolysis concentrations of PIC and QUIN were 0.017 +/- 0.005 and 0.018 +/- 0.006 micromol/L, respectively, which rose to 0.30 +/- 0.06 and 0.06 +/- 0.008 micromol/L respectively, after hydrolysis. In CSF samples from patients with a range of brain oedema or injury (eg subdural haemorrage, motor vehicle accident) (n=6) pre-hydrolysis concentrations of PIC and QUIN were 0.053 +/- 0.03 and 0.29 +/- 0.12 micromol/L, respectively. Following hydrolysis the concentrations were markedly increased to 6.06 +/- 1.5 and 0.94 +/- 0.63 micromol/L, respectively. The present investigation has shown for the first time that PAM and QAM are present endogenously with PAM being relatively higher than QAM, especially in CSF samples from patients with presumed brain inflammation. The site and mechanism of amidation of PIC and QUIN needs investigation.

The effects of picolinic acid and pH on the adsorption of Cu(II) by activated carbon fibers

The adsorption characteristics of Cu(II) on activated carbon fibers (ACFs) from simulated wastewater was investigated in the picolinic acid concentration range from 0.15 to 15 mM by varying pH from 2 to 8. When pH is below 4, the removal fraction of Cu(II) ions decreased with the decrease of pH. The removal fraction of Cu(II) ions is almost constant above pH 4. The removal efficiency of Cu(II) ions increased as the molar ratio of picolinic acid to Cu(II), specific surface area of ACFs and pH of the solution increased. In the case of [Pic]/[Cu(II)]=10, complete adsorption of Cu(II) was performed on ACF, even at pH 2.

Effect of intracellular iron depletion by picolinic acid on expression of the lactoferrin receptor in the human colon carcinoma cell subclone HT29-18-C1.

A lactoferrin receptor has been found on the brush-border membrane of intestinal epithelial cells of several species, including humans. A role for this receptor in intestinal iron absorption, which is well regulated in response to body iron stores, has been proposed. We have investigated the effect of intracellular iron depletion by picolinic acid, an iron chelator, on the cell surface binding of human lactoferrin to human enterocytes and its intracellular uptake, using HT29-18-C1 cells, an enterocyte-like differentiable cell line. The confluent cells exhibited 5.8 x 10(6) specific binding sites per cell for diferric human 125I-labelled lactoferrin with relatively low affinity (Kd 8.4 x 10(-7) M). The addition of picolinic acid to the culture medium resulted in a concentration- and time-dependent increase in lactoferrin binding that was correlated with a decrease in intracellular iron content. The maximum effect of picolinic acid on lactoferrin binding (approx. 2-fold increase), which appeared between 12 and 18 h after its addition, was obtained at a picolinic acid concentration of 2 mM. Scatchard analysis showed that the enhanced lactoferrin binding resulted from an increase in the number of lactoferrin receptors rather than an alteration in the binding affinity for lactoferrin. The time-dependent effect of picolinic acid was completely abolished in the presence of 1 microM anisomycin, a protein synthesis inhibitor, indicating that ongoing protein synthesis is involved in this effect. The enhanced lactoferrin binding induced by picolinic acid produced an increase of approx. 30% in the uptake of lactoferrin-bound 59Fe, indicating the existence of functional receptors. These results suggest that biosynthesis of lactoferrin receptors in intestinal epithelial cells can be regulated in response to the levels of intracellular chelatable iron, consistent with intestinal iron absorption dependent on body iron stores.

Separation of metal ions by reversed-phase liquid chromatography using on-column complexation with 2-pyridinecarboxylic acid

Picolinic acid was used as an on-column chelating agent for the reversed-phase liquid chromatographic separation of manganese(II), copper(II), nickel(II), cobalt(II), cadmium(II) and zinc(II). The effects of picolinic acid concentration, pH and type and content of organic solvent on the retention of transition metal ions have been studied. The possibility of sensitive UV detection of complexes at 235 nm is demonstrated. Data on the use of studied system for the determination of some metal ions in a galvanic bath waste water are presented.