Investigation of Genetic Variants Associated with Tryptophan Metabolite Levels via Serotonin and Kynurenine Pathways in Patients with Bipolar Disorder

The kynurenine pathway (KP) may play a role in the pathophysiology of bipolar disorder (BD). We conducted a genome-wide association study (GWAS) to identify genetic variants associated with the plasma levels of the metabolites of tryptophan (TRP) via the serotonin (5-HT) and kynurenine (KYN) pathways in 44 patients with BD and 45 healthy controls. We assessed whether variants that were differentially associated with metabolite levels based on the diagnostic status improved the prediction accuracy of BD using penalized regression approaches. We identified several genetic variants that were significantly associated with metabolites (5-HT, 5-hydroxytryptophan (5-HTP), TRP, and quinolinic acid (QA) or metabolite ratios (5-HTP/TRP and KYN/TRP) and for which the diagnostic status exerted a significant effect. The inclusion of genetic variants led to increased accuracy in the prediction of the BD diagnostic status. Specifically, we obtained an accuracy of 0.77 using Least Absolute Shrinkage and Selection Operator (LASSO) regression. The predictors retained as informative in this model included body mass index (BMI), the levels of TRP, QA, and 5-HT, the 5-HTP/TRP ratio, and genetic variants associated with the levels of QA (rs6827515, rs715692, rs425094, rs4645874, and rs77048355) and TRP (rs292212) or the 5-HTP/TRP ratio (rs7902231). In conclusion, our study identified statistically significant associations between metabolites of TRP via the 5-HT and KYN pathways and genetic variants at the genome-wide level. The discriminative performance of penalized regression models incorporating clinical, genetic, and metabolic predictors warrants a follow-up analysis of this panel of determinants

Composition of unfermented, unroasted, roasted cocoa beans and cocoa shells from Peninsular Malaysia

Composition of cocoa beans depends on origin and cocoa processing such as fermentation, drying and roasting. However, less research has been conducted to analyse the composition of Peninsular Malaysia cocoa bean at different processing stages. Thus, the purpose of this study was to determine the proximate, phytosterol level, antioxidant content and activity of Peninsular Malaysia unfermented, unroasted, roasted cocoa beans and cocoa shells. Analysis involved was proximate analysis, total phenolic compound (Folin–Ciocalteu reagent assay), antioxidant activity (2,2-diphenyl-1-picrylhydrazyl scavenging assay) and phytosterol composition. Results show that the crude fiber of unroasted cocoa beans and cocoa shells increased from 17.19 to 28.45% and 13.86 to 16.06% respectively after roasting process. The roasting process is suspected to increase the dietary fiber content of cocoa products due to the interaction between polysaccharides, protein, polyphenolic and Maillard products at high temperature. The total phenolic content in cocoa bean and cocoa shells ranged from 2.42 to 10.82 µg GAE/ml. The unfermented cocoa beans contain significantly (p < 0.05) higher antioxidant activity (92.3%) compared to other samples. This study shows that cholesterol, stigmasterol and β-sitosterol were present in roasted cocoa beans and cocoa shells. Hence, the information on the composition of Malaysia unfermented, unroasted, roasted cocoa beans and cocoa shells are needed to enrich the databases composition as a reference for the cocoa industry

The role of peptides and proteins in melanoidin formation

High-molecular-weight (HMW) coloured compounds called melanoidins are widely distributed, particularly in foods. It has been proposed that they originate through the Maillard reaction, a non-enzymatic browning reaction, due to the interaction between protein or peptide amino groups and carbohydrates. The melanoidin structure is not definitively known, and they have been generally defined as HMW nitrogen-containing brown polymers. In order to gain information on the nature of melanoidins, a simple in vitro model was chosen to investigate the products of the reactions between sugars and peptide/proteins. This approach would elucidate whether melanoidin formation is due to the binding of different sugar units to a peptide/protein or vice versa. With this aim, the reactivity of two different peptides, EPK177 and physalaemin, and a low-molecular-weight (LMW) protein, lysozyme, was tested towards different saccharides (glucose, maltotriose (MT), maltopentaose and dextran 1000) in aqueous solutions at different temperatures. The incubation mixtures were analysed at different reaction times by MALDI/MS. Furthermore, in order to verify the possible role of sugar pyrolysis products in melanoidin formation, the products arising from the thermal treatment at 200 degrees C of MT were incubated with lysozyme, and the reaction products were analysed by the same MS approach. The obtained results allowed the establishment of some general views: melanoidins cannot simply originate by reactions of sugar moieties with proteins. In fact, the reaction easily occurs, but it does not lead to any coloured product, as melanoidins have been described to be; melanoidins cannot originate from the thermal degradation products of glycated proteins. In fact, the thermal treatment of glycated lysozyme leads to a severe degradation of the protein with the formation of LMW species, far from the view of melanoidins as HMW compounds; experimental evidence has been gained on the melanoidin formation through reaction of intact protein with the pyrolysis products of MT. This hypothesis has been supported either from MALDI measurements or from spectroscopic data that show an absorption band in the range 300-600 nm, typical of melanoidins