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Modelling of metabolic control by Short Chain Fatty Acids at the level of the functional proteomic analysis

Published online by Cambridge University Press:  30 August 2013

L. E. Sánchez-Mejorada Zúñiga ,
Joanne Connolly ,
Kelly McMahon ,
C. A. Evans  and
B. M. Corfe
L. E. Sánchez-Mejorada Zúñiga
Affiliation:
Molecular Gastroenterology Research Group, Academic Unit of Surgical Oncology, Department of Oncology, The Medical School, Beech Hill Road, Sheffield, S10 2RX Biological and Systems Engineering Group, ChELSI Institute, Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, S1 3JD
Joanne Connolly
Affiliation:
Waters Corporation, Floats Rd, Manchester, Lancashire M23 9LZ, UK
Kelly McMahon
Affiliation:
Waters Corporation, Floats Rd, Manchester, Lancashire M23 9LZ, UK
C. A. Evans
Affiliation:
Biological and Systems Engineering Group, ChELSI Institute, Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, S1 3JD
B. M. Corfe
Affiliation:
Molecular Gastroenterology Research Group, Academic Unit of Surgical Oncology, Department of Oncology, The Medical School, Beech Hill Road, Sheffield, S10 2RX
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Abstract

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Abstract
Information
Proceedings of the Nutrition Society , Volume 72 , Issue OCE4: Summer Meeting, 15–18 July 2013, Nutrition and healthy ageing , 2013 , E229
Copyright
Copyright © The Authors 2013 

Dietary residues are fermented in the large intestine to produce short-chain fatty acids (SCFAs) in the colon( Reference Lupton 1 , Reference Scheppach, Bartram and Richter2 , Reference Hague, Butt and Paraskeva3 ). SCFAs, particularly butyrate, inhibit histone deacetylation, may be chemopreventive, and regulate acetylation of metabolic pathways( Reference Candido, Reeves and Davies 4 , Reference Lea and Randolph5 , Reference Donohoe, Collins and Wali6 , Reference Bingham7 , Reference Jahns, Wilhelm and Jablonowski8 ). As metabolic pathways are subject of being regulated by acetylation( Reference Xiong, Lei and Zhao 9 ), it is possible to model and elucidate the interaction among the diverse metabolic pathways and their acetylation patterns.

Mitochondrially enriched fractions from HCT116 colon cancer cells treated with 10 mM propionate and/or butyrate in a 2×2 factorial design with two independent repeats were analysed using a label-free workflow. The total proteome and acetylated proteome were identified and the data interrogated qualitatively as a first step using ProteinLynxGlobal Server and Scaffold software packages. Representation analysis was undertaken DAVID and Reactome. Enzymes for major metabolic pathways involving acetyl-CoA (as a component: Glycolysis, Tricarboxylic Acid, Pyruvate metabolism and β-oxidation) were searched for by Uniprot identifier.

Representation analysis indicated translation pathways were particularly enriched in the global proteome (P=1.6×10−59) suggesting presence of ribosomes in the fractions. All metabolic pathways were represented with 65% coverage for Glycolysis, 81% for TCA, and 55% for β-oxidation. The acetylated proteome was further enriched for translation (P=1.6×10−3). All metabolic pathways were represented in the acetylated proteome with 23% for Glycolysis, 19% for TCA, and 18% for β-oxidation. Principal Components Analysis (PCA) showed good clustering of replicates and a marked difference between the effects of propionate and butyrate.

The data suggest that the translational apparatus is highly acetylated and therefore may represent an additional level of functional control by SCFA related to transcriptions in cellular programming. The PCA data confirm our published findings that butyrate and propionate have distinct rather than graded cellular effects. Datamining is underway to establish whether spectra for acetylpeptides in the metabolic enzymes exhibit altered counts after treatments.

References

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