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GROWTH RATE DEPENDENT CARBON CATABOLITE REPRESSION (CCR) IS DETERMINED BY MOLECULAR CROWDING (MC) IN E. COLI CELLS

Zhou, Yi (2011) GROWTH RATE DEPENDENT CARBON CATABOLITE REPRESSION (CCR) IS DETERMINED BY MOLECULAR CROWDING (MC) IN E. COLI CELLS. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Carbon catabolite repression (CCR) in bacterial cells leads to their selective consumption of a single substrate from a complex environment, but the evolutionary origin of this regulatory mechanism is unknown. Previously, a flux balance model that takes into account the crowded intracellular milieu of the cell (molecular crowding constraint) have correctly predicted selective glucose uptake in a medium containing five different carbon sources, suggesting that CCR might have evolved to ensure optimal metabolic network activity for growth. Here, we show that CCR is evident in rapidly proliferating cells grown in both mixed- and single carbon-limited cultures, and that in increasingly rapidly proliferating cells the gradual activation of CCR correlates with the appearance of a metabolic switch from oxidative phosphorylation (OxPhos) toward aerobic glycolysis. Thus, macromolecular crowding in the cell represents the root cause of both CCR and the “OxPhos to glycolysis” switch evolved to ensure optimal cell metabolism.

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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Zhou, Yiyizhou.yi@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairZarnegar, Rezarezazar@pitt.edu REZAZAR
Thesis AdvisorOltvai, Zoltanoltvai@pitt.eduOLTVAI
Committee MemberVodovotz, Yoramvodovotzy@upmc.edu
Committee MemberJudith Hendrike, Kleinjudithks@cs.cmu.edu
Committee MemberKaminski, Naftalikaminskin@upmc.edu
Committee MemberBar-Joseph, Zivzivbj@cs.cmu.edu
Date: 20 December 2011
Date Type: Publication
Defense Date: 9 December 2011
Approval Date: 20 December 2011
Submission Date: 19 December 2011
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 128
Institution: University of Pittsburgh
Schools and Programs: School of Medicine > Cellular and Molecular Pathology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: CCR, FBA, FBAwMC, molecular crowding, metabolism, E. coli cells
Date Deposited: 20 Dec 2011 20:51
Last Modified: 15 Nov 2016 13:55
URI: http://d-scholarship.pitt.edu/id/eprint/10840

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