Indian Institute of Technology Palakkad&nbsp;(IIT Palakkad or IIT PKD) is a public autonomous&nbsp;engineering&nbsp;and&nbsp;research&nbsp;institute located in&nbsp;Palakkad,&nbsp;Kerala. It was&nbsp;one of the five new&nbsp;IITs&nbsp;proposed in the&nbsp;2014 Union budget of India. The campus was inaugurated on 3 August 2015. The institute has 94 faculty, 978 students, and 63 non-teaching staffs.

IT Palakkad currently offers four-year Bachelor of Technology (B.Tech) and two years MS programmes in 8 different engineering disciplines including&nbsp;Computer Science, Electrical, Mechanical, Civil among others.

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IIT Palakkad

Metabolomics is a data-based research strategy, the aims of which are to identify biomarker pictures of metabolic systems and metabolic perturbations and to formulate hypotheses to be tested. It involves the assay by mass spectrometry or NMR of many metabolites present in the biological system investigated. In this minireview, we outline studies in which metabolomics led to useful biomarkers of metabolic processes. We also illustrate how the discovery potential of metabolomics is enhanced by associating it with stable isotopic techniques. © 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

World University root node

Department of Chemistry

Fulltext

Journal of Biological Chemistry

Metabolomics, pathway regulation, and pathway discovery

(Figure Presented) 4-Hydroxyacids are ubiquitous in human physiology. They are derived from the drugs of abuse γ-hydroxybutyrate (GHB), γ-hydroxypentanoate(GHP), in addition to the omnipresent lipid peroxidation product 4-hydroxy-2-(E)-nonenal (4-HNE). Previously we reported that 4-hydroxyacids are catabolized through two parallel pathways. In this report we detail two isotopic tools that have allowed the dissection of this catabolic process and illustrate how these tools can be used to quantify the relative flux down each pathway. We found that 4-hydroxynonanoate (4-hydroxyacid derived from 4-HNE) is primarly catabolized through a pathway that phosphorylates the C-4 hydroxyl and isomerizes it to a C-3 hydroxy compound, which is catabolized through β-oxidation. © 2010 American Chemical Society.

Journal of the American Chemical Society

Using isotopic tools to dissect and quantitate parallel metabolic pathways

A drug library of 17200 compounds was screened to select small molecules that inhibit the secretion of amyloid β peptide (Aβ), the major component of Alzheimer disease senile plaques, from a human neuronal cell line. Twenty-nine hits were validated that decreased Aβ secretion by >40% at 10 μM, for a 0.17% hit rate. A lead hit was selected for further study based on its activity and low cytotoxicity, and it was found to inhibit Aβ secretion through activation of the α-secretase pathway. Twenty-four commercially available and 53 synthesized analogues were analyzed for activity. Selected analogues were evaluated for biological stability by incubation with hepatoma cells and for transcellular permeability using Caco-2 cell monolayers. The analogue with the best permeability was evaluated in 2-month old amyloid precursor protein transgenic mice and found to acutely reduce cerebral Aβ levels by 40% after a single iv administration. © 2010 American Chemical Society.

Journal of Medicinal Chemistry

Synthesis and biological evaluation of analogues of a novel inhibitor of β-amyloid secretion

ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY

Metabolism of 4-hydroxy acids and 4-hydroxynonenal using a selective isotope labeling strategy

The FASEB Journal

Partial beta‐oxidation and bilateral alpha‐oxidation of gamma‐hydroxybutyrate (GHB) in perfused rat livers

Tetrahedron

The syntheses and applications of β-benzylmercaptoethylamine derivatives

4-Hydroxyacids are products of ubiquitously occurring lipid peroxidation (C9, C6) or drugs of abuse (C4, C5). We investigated the catabolism of these compounds using a combination of metabolomics and mass isotopomer analysis. Livers were perfused with various concentrations of unlabeled and labeled saturated 4-hydroxyacids (C4 to C11) or 4-hydroxynonenal. All the compounds tested form a new class of acyl-CoA esters, 4-hydroxy-4-phosphoacyl-CoAs, characterized by liquid chromatography-tandem mass spectrometry, accurate mass spectrometry, and 31P-NMR. All 4-hydroxyacids with five or more carbons are metabolized by two new pathways. The first and major pathway, which involves 4-hydroxy-4-phosphoacyl-CoAs, leads in six steps to the isomerization of 4-hydroxyacyl-CoA to 3-hydroxyacyl-CoAs. The latter are intermediates of physiological β-oxidation. The second and minor pathway involves a sequence of β-oxidation, β-oxidation, and β-oxidation steps. In mice deficient in succinic semialdehyde dehydrogenase, high plasma concentrations of 4-hydroxybutyrate result in high concentrations of 4-hydroxy-4-phospho-butyryl-CoA in brain and liver. The high concentration of 4-hydroxy-4-phospho-butyryl-CoA may be related to the cerebral dysfunction of subjects ingesting 4-hydroxybutyrate and to the mental retardation of patients with 4-hydroxybutyric aciduria. Our data illustrate the potential of the combination of metabolomics and mass isotopomer analysis for pathway discovery. © 2009 by The American Society for Biochemistry and Molecular Biology, Inc.

Catabolism of 4-hydroxyacids and 4-hydroxynonenal via 4-hydroxy-4-phosphoacyl-CoAs

Use of vinyl acetate as acyl donor in transesterification of benzyl alcohol catalyzed by a commercially available lipase (Lipozyme® RM IM) gave 100% conversion in 10 min. The excess acyl donor and the enzyme could be recovered and reused. Unlike the chemical catalytic processes, it produced no undesirable side product. © 2006 Elsevier Ltd. All rights reserved.