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Isotopically nonstationary 13C flux analysis of Myc-induced metabolic reprogramming in B-cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
31664 44827 2013 12 PDF Available
Title
Isotopically nonstationary 13C flux analysis of Myc-induced metabolic reprogramming in B-cells
Abstract

We assessed several methods of 13C metabolic flux analysis (MFA) and found that isotopically nonstationary MFA achieved maximum flux resolution in cultured P493-6 B-cells, which have been engineered to provide tunable expression of the Myc oncoprotein. Comparison of metabolic flux maps obtained under oncogenic (High) and endogenous (Low) Myc expression levels revealed network-wide reprogramming in response to ectopic Myc expression. High Myc cells relied more heavily on mitochondrial oxidative metabolism than Low Myc cells and globally upregulated their consumption of amino acids relative to glucose. TCA cycle and amphibolic mitochondrial pathways exhibited 2- to 4-fold flux increases in High Myc cells, in contrast to modest increases in glucose uptake and lactate excretion. Because our MFA approach relied exclusively upon isotopic measurements of protein-bound amino acids and RNA-bound ribose, it is readily applicable to more complex tumor models that are not amenable to direct extraction and isotopic analysis of free intracellular metabolites.

► Isotopically nonstationary MFA provided maximum flux resolution in cultured B-cells. ► Flux maps were compared under oncogenic (High) and endogenous (Low) Myc expression. ► High Myc cells relied more heavily on oxidative phosphorylation than Low Myc cells. ► High Myc cells also upregulated their consumption of amino acids relative to glucose. ► MFA approach relied on labeling patterns of hydrolyzed protein and RNA constituents.

Keywords
AcCoA, Acetyl-Coenzyme A; AcCoA.C, cytosolic Acetyl-Coenzyme A; ACL, ATP-citrate lyase; ADH, α-ketoglutarate dehydrogenase; AKG, α-ketoglutarate; ALA, alanine; ARG, arginine; ASP, aspartate; CIT, citrate; FUM, fumarate; G6P, glucose-6-phosphate; G6PDH, gl
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Isotopically nonstationary 13C flux analysis of Myc-induced metabolic reprogramming in B-cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 15, January 2013, Pages 206–217
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us