Inhibition kinetics of catabolic dehydrogenases by elevated moieties of ATP and ADP - implication for a new regulation mechanism in Lactococcus lactis
(2010) In The FEBS Journal 277(8). p.1843-1852- Abstract
- ATP and ADP inhibit, in varying degrees, several dehydrogenases of the
central carbon metabolism of Lactococcus lactis ATCC 19435 in vitro, i.e.
glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase
(LDH) and alcohol dehydrogenase (ADH). Here we demonstrate
mixed inhibition for GAPDH and competitive inhibition for LDH and
ADH by adenine nucleotides in single inhibition studies. The nonlinear
negative co-operativity was best modelled with Hill-type kinetics, showing
greater flexibility than the usual parabolic inhibition equation. Because
these natural inhibitors are present simultaneously in the cytoplasm, multiple
inhibition kinetics was... (More) - ATP and ADP inhibit, in varying degrees, several dehydrogenases of the
central carbon metabolism of Lactococcus lactis ATCC 19435 in vitro, i.e.
glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase
(LDH) and alcohol dehydrogenase (ADH). Here we demonstrate
mixed inhibition for GAPDH and competitive inhibition for LDH and
ADH by adenine nucleotides in single inhibition studies. The nonlinear
negative co-operativity was best modelled with Hill-type kinetics, showing
greater flexibility than the usual parabolic inhibition equation. Because
these natural inhibitors are present simultaneously in the cytoplasm, multiple
inhibition kinetics was determined for each dehydrogenase. For ADH
and LDH, the inhibitor combinations ATP plus NAD and ADP plus
NAD are indifferent to each other. Model discrimination suggested that
the weak allosteric inhibition of GAPDH had no relevance when multiple
inhibitors are present. Interestingly, with ADH and GAPDH the combination
of ATP and ADP exhibits lower dissociation constants than with
either inhibitor alone. Moreover, the concerted inhibition of ADH and
GAPDH, but not of LDH, shows synergy between the two nucleotides.
Similar kinetics, but without synergies, were found for horse liver and yeast
ADHs, indicating that dehydrogenases can be modulated by these nucleotides
in a nonlinear manner in many organisms. The action of an elevated
pool of ATP and ADP may effectively inactivate lactococcal ADH, but
not GAPDH and LDH, providing leverage for the observed metabolic shift
to homolactic acid formation in lactococcal resting cells on maltose. Therefore,
we interpret these results as a regulation mechanism contributing to
readjusting the flux of ATP production in L. lactis. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1581335
- author
- Cao, Rong LU ; Zeidan, Ahmad LU ; Rådström, Peter LU and van Niel, Ed LU
- organization
- publishing date
- 2010
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- ATP, ADP, Lactococcus lactis, multiple inhibition kinetics, dehydrogenase
- in
- The FEBS Journal
- volume
- 277
- issue
- 8
- pages
- 1843 - 1852
- publisher
- Wiley-Blackwell
- external identifiers
-
- wos:000276168800006
- scopus:77950496679
- pmid:20193044
- ISSN
- 1742-464X
- DOI
- 10.1111/j.1742-4658.2010.07601.x
- language
- English
- LU publication?
- yes
- id
- e35b6038-c4c3-430a-a9b2-2a7fa5268579 (old id 1581335)
- date added to LUP
- 2016-04-01 14:09:08
- date last changed
- 2022-01-27 23:01:22
@article{e35b6038-c4c3-430a-a9b2-2a7fa5268579,
abstract = {{ATP and ADP inhibit, in varying degrees, several dehydrogenases of the<br/><br>
central carbon metabolism of Lactococcus lactis ATCC 19435 in vitro, i.e.<br/><br>
glyceraldehyde-3-phosphate dehydrogenase (GAPDH), lactate dehydrogenase<br/><br>
(LDH) and alcohol dehydrogenase (ADH). Here we demonstrate<br/><br>
mixed inhibition for GAPDH and competitive inhibition for LDH and<br/><br>
ADH by adenine nucleotides in single inhibition studies. The nonlinear<br/><br>
negative co-operativity was best modelled with Hill-type kinetics, showing<br/><br>
greater flexibility than the usual parabolic inhibition equation. Because<br/><br>
these natural inhibitors are present simultaneously in the cytoplasm, multiple<br/><br>
inhibition kinetics was determined for each dehydrogenase. For ADH<br/><br>
and LDH, the inhibitor combinations ATP plus NAD and ADP plus<br/><br>
NAD are indifferent to each other. Model discrimination suggested that<br/><br>
the weak allosteric inhibition of GAPDH had no relevance when multiple<br/><br>
inhibitors are present. Interestingly, with ADH and GAPDH the combination<br/><br>
of ATP and ADP exhibits lower dissociation constants than with<br/><br>
either inhibitor alone. Moreover, the concerted inhibition of ADH and<br/><br>
GAPDH, but not of LDH, shows synergy between the two nucleotides.<br/><br>
Similar kinetics, but without synergies, were found for horse liver and yeast<br/><br>
ADHs, indicating that dehydrogenases can be modulated by these nucleotides<br/><br>
in a nonlinear manner in many organisms. The action of an elevated<br/><br>
pool of ATP and ADP may effectively inactivate lactococcal ADH, but<br/><br>
not GAPDH and LDH, providing leverage for the observed metabolic shift<br/><br>
to homolactic acid formation in lactococcal resting cells on maltose. Therefore,<br/><br>
we interpret these results as a regulation mechanism contributing to<br/><br>
readjusting the flux of ATP production in L. lactis.}},
author = {{Cao, Rong and Zeidan, Ahmad and Rådström, Peter and van Niel, Ed}},
issn = {{1742-464X}},
keywords = {{ATP; ADP; Lactococcus lactis; multiple inhibition kinetics; dehydrogenase}},
language = {{eng}},
number = {{8}},
pages = {{1843--1852}},
publisher = {{Wiley-Blackwell}},
series = {{The FEBS Journal}},
title = {{Inhibition kinetics of catabolic dehydrogenases by elevated moieties of ATP and ADP - implication for a new regulation mechanism in Lactococcus lactis}},
url = {{https://lup.lub.lu.se/search/files/3817006/1581336.pdf}},
doi = {{10.1111/j.1742-4658.2010.07601.x}},
volume = {{277}},
year = {{2010}},
}