PMID- 22920924
OWN - NLM
STAT- MEDLINE
DCOM- 20130220
LR  - 20211021
IS  - 1752-0509 (Electronic)
IS  - 1752-0509 (Linking)
VI  - 6
DP  - 2012 Aug 24
TI  - Exploring the genetic control of glycolytic oscillations in Saccharomyces 
      cerevisiae.
PG  - 108
LID - 10.1186/1752-0509-6-108 [doi]
AB  - BACKGROUND: A well known example of oscillatory phenomena is the transient 
      oscillations of glycolytic intermediates in Saccharomyces cerevisiae, their 
      regulation being predominantly investigated by mathematical modeling. To our 
      knowledge there has not been a genetic approach to elucidate the regulatory role 
      of the different enzymes of the glycolytic pathway. RESULTS: We report that the 
      laboratory strain BY4743 could also be used to investigate this oscillatory 
      phenomenon, which traditionally has been studied using S. cerevisiae X2180. This 
      has enabled us to employ existing isogenic deletion mutants and dissect the roles 
      of isoforms, or subunits of key glycolytic enzymes in glycolytic oscillations. We 
      demonstrate that deletion of TDH3 but not TDH2 and TDH1 (encoding 
      glyceraldehyde-3-phosphate dehydrogenase: GAPDH) abolishes NADH oscillations. 
      While deletion of each of the hexokinase (HK) encoding genes (HXK1 and HXK2) 
      leads to oscillations that are longer lasting with lower amplitude, the effect of 
      HXK2 deletion on the duration of the oscillations is stronger than that of HXK1. 
      Most importantly our results show that the presence of beta (Pfk2) but not that 
      of alpha subunits (Pfk1) of the hetero-octameric enzyme phosphofructokinase (PFK) 
      is necessary to achieve these oscillations. Furthermore, we report that the 
      cAMP-mediated PKA pathway (via some of its components responsible for feedback 
      down-regulation) modulates the activity of glycoytic enzymes thus affecting 
      oscillations. Deletion of both PDE2 (encoding a high affinity 
      cAMP-phosphodiesterase) and IRA2 (encoding a GTPase activating protein- Ras-GAP, 
      responsible for inactivating Ras-GTP) abolished glycolytic oscillations. 
      CONCLUSIONS: The genetic approach to characterising the glycolytic oscillations 
      in yeast has demonstrated differential roles of the two types of subunits of PFK, 
      and the isoforms of GAPDH and HK. Furthermore, it has shown that PDE2 and IRA2, 
      encoding components of the cAMP pathway responsible for negative feedback 
      regulation of PKA, are required for glycolytic oscillations, suggesting an 
      enticing link between these cAMP pathway components and the glycolysis pathway 
      enzymes shown to have the greatest role in glycolytic oscillation. This study 
      suggests that a systematic genetic approach combined with mathematical modelling 
      can advance the study of oscillatory phenomena.
FAU - Williamson, Thomas
AU  - Williamson T
AD  - Faculty of Life Sciences, University of Manchester, Manchester, M13 9PT, UK.
FAU - Adiamah, Delali
AU  - Adiamah D
FAU - Schwartz, Jean-Marc
AU  - Schwartz JM
FAU - Stateva, Lubomira
AU  - Stateva L
LA  - eng
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120824
PL  - England
TA  - BMC Syst Biol
JT  - BMC systems biology
JID - 101301827
RN  - 0 (Isoenzymes)
RN  - 0U46U6E8UK (NAD)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - EC 2.7.1 - (Phosphofructokinases)
RN  - EC 2.7.1.1 (Hexokinase)
SB  - IM
MH  - Cyclic AMP/metabolism
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/deficiency/genetics
MH  - Glycolysis/*genetics
MH  - Hexokinase/deficiency/genetics
MH  - Isoenzymes/deficiency/genetics
MH  - *Models, Genetic
MH  - NAD/metabolism
MH  - Phosphofructokinases/deficiency/genetics
MH  - Saccharomyces cerevisiae/cytology/enzymology/*genetics/*metabolism
MH  - Sequence Deletion
MH  - Signal Transduction/genetics
PMC - PMC3497587
EDAT- 2012/08/28 06:00
MHDA- 2013/02/21 06:00
PMCR- 2012/08/24
CRDT- 2012/08/28 06:00
PHST- 2012/04/03 00:00 [received]
PHST- 2012/07/24 00:00 [accepted]
PHST- 2012/08/28 06:00 [entrez]
PHST- 2012/08/28 06:00 [pubmed]
PHST- 2013/02/21 06:00 [medline]
PHST- 2012/08/24 00:00 [pmc-release]
AID - 1752-0509-6-108 [pii]
AID - 10.1186/1752-0509-6-108 [doi]
PST - epublish
SO  - BMC Syst Biol. 2012 Aug 24;6:108. doi: 10.1186/1752-0509-6-108.