Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma of medication-free patients with major depressive disorder

Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) is a comprehensive, quantitative, and high throughput tool used to analyze metabolite profiles. In the present study, we used CE-TOFMS to profile metabolites found in the blood plasma of 33 medication-free patients with major depressive disorder (MDD) and 33 non-psychiatric control subjects. We then investigated changes which occurred in the metabolite levels during an 8-week treatment period. The medication-free MDD patients and control subjects showed significant differences in their mean levels of 33 metabolites, including kynurenine (KYN), glutamate (Glu), glutamine (Gln), methionine sulfoxide, and methionine (Met). In particular, the ratios of KYN to tryptophan (TRP), Gln to Glu, and Met to methionine sulfoxide were all significantly different between the two groups. Among the 33 metabolites with altered levels in MDD patients, the levels of KYN and Gln, as well as the ratio of Gln to Glu, were significantly normalized after treatment. Our findings suggest that imbalances in specific metabolite levels may be involved in the pathogenesis of MDD, and provide insight into the mechanisms by which antidepressant agents work in MDD patients

Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma of medication-free patients with major depressive disorder

Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) is a comprehensive, quantitative, and high throughput tool used to analyze metabolite profiles. In the present study, we used CE-TOFMS to profile metabolites found in the blood plasma of 33 medication-free patients with major depressive disorder (MDD) and 33 non-psychiatric control subjects. We then investigated changes which occurred in the metabolite levels during an 8-week treatment period. The medication-free MDD patients and control subjects showed significant differences in their mean levels of 33 metabolites, including kynurenine (KYN), glutamate (Glu), glutamine (Gln), methionine sulfoxide, and methionine (Met). In particular, the ratios of KYN to tryptophan (TRP), Gln to Glu, and Met to methionine sulfoxide were all significantly different between the two groups. Among the 33 metabolites with altered levels in MDD patients, the levels of KYN and Gln, as well as the ratio of Gln to Glu, were significantly normalized after treatment. Our findings suggest that imbalances in specific metabolite levels may be involved in the pathogenesis of MDD, and provide insight into the mechanisms by which antidepressant agents work in MDD patients

Cysteine string protein 1 (CSP1) modulates insulin sensitivity by attenuating glucose transporter 4 (GLUT4) vesicle docking with the plasma membrane

Insulin stimulates glucose transporter 4 (GLUT4) vesicle recruitment from its intracellular storage site to the plasma membrane. Cysteine string protein 1 (CSP1) is a SNARE-binding protein involved in the vesicular trafficking of neurotransmitters and other exocytic processes. In this study, we investigated the involvement of CSP1 in insulin-dependent GLUT4 recruitment in 3T3-L1 adipocytes. Over-expression of wild-type CSP1 led to attenuated insulin-stimulated glucose uptake without any change in GLUT4 content in the plasma membrane, rather it inhibits docking by blocking the association of VAMP2 with syntaxin 4. In contrast, knockdown of CSP1 enhanced insulin-stimulated glucose uptake. The mRNA and protein expression of CSP1 was elevated in 3T3-L1 adipocytes in insulin resistant states caused by high levels of palmitate and chronic insulin exposure. Taken together, the results of this study suggest that CSP1 is involved in insulin resistance by interrupting GLUT4 vesicle docking with the plasma membrane

Exploration of Dimethylzinc-Mediated Radical Reactions.

Article first published online: 17 JUL 2015In this account, our studies on radical reactions that are promoted by dimethylzinc and air are described. Advantages of this reagent and differences from conventional radical initiators, such as triethylborane, are discussed

Steric influence of N-phosphorus-arylimines on the rhodium-catalyzed asymmetric arylation

Examination of the rhodium-catalyzed asymmetric arylation of benzaldehyde-imines bearing ethoxy, isopropoxy, phenyl, cyclohexyl, 3, 5-xylyl, and 2, 4, 6-mesityl N-phosphorus activating/protecting groups revealed that bulky N-phosphorus groups retarded the arylation and at the same time prevented the competitive hydrolysis of an imine. Although the level of enantioselectivity was dependent favorably on the bulkiness ranging from 88% ee to 53% ee, the reactivity was drastically decreased along with bulkiness ranging from 95% to 3%

Rhodium-catalyzed asymmetric phenylation of N-phosphinoylarylimines with triphenylborane

Triphenylborane asymmetrically transfers its phenyl group to N-diphenylphosphinoylarylimines to give diarylmethylamines with high ee in high yield without imine hydrolysis under the catalysis of a chiral amidomonophosphane–rhodium(I) complex

Critical profiles of chiral diether-mediated asymmetric conjugate aminolithiation of enoate with lithium amide as a key to the total synthesis of (−)-kopsinine

Chiral diether-mediated asymmetric aminolithiation of indolylpropenoate with lithium amide in toluene at -78 °C for 15 min gave, after aqueous ammonium chloride quench, the corresponding conjugate addition product with 97% ee in 89% yield. If hydrogen chloride in methanol was selected as a quencher, however, aminolithiation at -78 °C for 3 h gave the corresponding adduct with 97% ee in 54% yield, along with recovery of the starting enoate in 39% yield. Based on this finding of an incomplete and slow reaction at -78 °C, the aminolithiation conditions were optimized to be at -60 °C for 15 h and subsequent enolate trap with alkyl halide upon an addition of DMPU afforded the desired aminoalkylation product with 98% ee in 89% yield. Further approach toward total synthesis of (−)-kopsinine was carried out by examining asymmetric aminolithiation with N-hydroxyethylamine equivalent, one-pot piperidine formation, and Claisen condensation