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Principles of Flux and Concentration Sensing in Metabolic Regulation
Principles of Flux and Concentration Sensing in Metabolic Regulation
Principles of Flux and Concentration Sensing in Metabolic Regulation

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자료유형  
 학위논문 서양
최종처리일시  
20250211152823
ISBN  
9798346533283
DDC  
574
저자명  
Palme, Julius.
서명/저자  
Principles of Flux and Concentration Sensing in Metabolic Regulation
발행사항  
[Sl] : Harvard University, 2024
발행사항  
Ann Arbor : ProQuest Dissertations & Theses, 2024
형태사항  
171 p
주기사항  
Source: Dissertations Abstracts International, Volume: 86-05, Section: B.
주기사항  
Advisor: Springer, Michael.
학위논문주기  
Thesis (Ph.D.)--Harvard University, 2024.
초록/해제  
요약To efficiently regulate metabolism, cells must continuously monitor and respond to their metabolic state. Cells are generally thought to achieve this monitoring by sensing metabolite concentrations. However, many cellular responses do not correlate with metabolite concentrations but with the fluxes through metabolic pathways. The mechanisms with which cells sense these metabolic fluxes have largely remained unclear. In chapter 2 of this thesis, we report that one of the most-studied eukaryotic nutrient sensing pathways, galactose-responsive (GAL) signaling of Saccharomyces cerevisiae, is regulated by galactose flux and that this flux sensing is achieved by a simple mechanism: The enzyme that catabolizes galactose has a signaling activity that is coupled to its catalytic activity, resulting in the proportionality of signaling and flux. This flux sensing has the critical physiological role of maintaining GAL signaling when cells catabolize galactose. Additionally, the GAL pathway is regulated by the intracellular galactose concentration which is sensed by a dedicated sensor protein. This concentration sensing has the separate physiological role of activating GAL signaling when cells first encounter galactose. In chapter 3 of this thesis, we show that concentration sensing is tuned by cellular and evolutionary history, determining whether all or only some cells of a population respond to galactose. Overall, flux and concentration sensing underlie distinct regulatory behaviors in the GAL pathway and their combination could be a recurrent motif of metabolic regulation.
일반주제명  
Biology
일반주제명  
Microbiology
일반주제명  
Biomedical engineering
키워드  
Saccharomyces cerevisiae
키워드  
Cellular responses
키워드  
Metabolic regulation
기타저자  
Harvard University Medical Sciences
기본자료저록  
Dissertations Abstracts International. 86-05B.
전자적 위치 및 접속  
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MARC

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■1001  ▼aPalme,  Julius.▼0(orcid)0000-0001-5897-1334
■24510▼aPrinciples  of  Flux  and  Concentration  Sensing  in  Metabolic  Regulation
■260    ▼a[Sl]▼bHarvard  University▼c2024
■260  1▼aAnn  Arbor▼bProQuest  Dissertations  &  Theses▼c2024
■300    ▼a171  p
■500    ▼aSource:  Dissertations  Abstracts  International,  Volume:  86-05,  Section:  B.
■500    ▼aAdvisor:  Springer,  Michael.
■5021  ▼aThesis  (Ph.D.)--Harvard  University,  2024.
■520    ▼aTo  efficiently  regulate  metabolism,  cells  must  continuously  monitor  and  respond  to  their  metabolic  state.  Cells  are  generally  thought  to  achieve  this  monitoring  by  sensing  metabolite  concentrations.  However,  many  cellular  responses  do  not  correlate  with  metabolite  concentrations  but  with  the  fluxes  through  metabolic  pathways.  The  mechanisms  with  which  cells  sense  these  metabolic  fluxes  have  largely  remained  unclear.  In  chapter  2  of  this  thesis,  we  report  that  one  of  the  most-studied  eukaryotic  nutrient  sensing  pathways,  galactose-responsive  (GAL)  signaling  of  Saccharomyces  cerevisiae,  is  regulated  by  galactose  flux  and  that  this  flux  sensing  is  achieved  by  a  simple  mechanism:  The  enzyme  that  catabolizes  galactose  has  a  signaling  activity  that  is  coupled  to  its  catalytic  activity,  resulting  in  the  proportionality  of  signaling  and  flux.  This  flux  sensing  has  the  critical  physiological  role  of  maintaining  GAL  signaling  when  cells  catabolize  galactose.  Additionally,  the  GAL  pathway  is  regulated  by  the  intracellular  galactose  concentration  which  is  sensed  by  a  dedicated  sensor  protein.  This  concentration  sensing  has  the  separate  physiological  role  of  activating  GAL  signaling  when  cells  first  encounter  galactose.  In  chapter  3  of  this  thesis,  we  show  that  concentration  sensing  is  tuned  by  cellular  and  evolutionary  history,  determining  whether  all  or  only  some  cells  of  a  population  respond  to  galactose.  Overall,  flux  and  concentration  sensing  underlie  distinct  regulatory  behaviors  in  the  GAL  pathway  and  their  combination  could  be  a  recurrent  motif  of  metabolic  regulation.
■590    ▼aSchool  code:  0084.
■650  4▼aBiology
■650  4▼aMicrobiology
■650  4▼aBiomedical  engineering
■653    ▼aSaccharomyces  cerevisiae
■653    ▼aCellular  responses
■653    ▼aMetabolic  regulation
■690    ▼a0306
■690    ▼a0541
■690    ▼a0410
■71020▼aHarvard  University▼bMedical  Sciences.
■7730  ▼tDissertations  Abstracts  International▼g86-05B.
■790    ▼a0084
■791    ▼aPh.D.
■792    ▼a2024
■793    ▼aEnglish
■85640▼uhttp://www.riss.kr/pdu/ddodLink.do?id=T17164028▼nKERIS▼z이  자료의  원문은  한국교육학술정보원에서  제공합니다.

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