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Difference between revisions of "Flux control efficiency"

From Bioblast
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== Coupling control factor ==
== Coupling control factor ==


:::: [[Coupling control factor]]s are determined in an [[ETS-competent pathway control state]].
:::: [[Coupling control factor]]s are determined in an [[ET-pathway competent state]].


=== mt-Preparations ===
=== mt-Preparations ===
:::: [[Image:P.jpg|link=OXPHOS capacity|OXPHOS]] [[Image:L.jpg|link=LEAK respiration|LEAK]] [[Image:E.jpg|link=ETS capacity|ETS]] In mitochondrial preparations, there are three well-defined coupling states of respiration, ''L'', ''P'', ''E'' ([[LEAK]], [[OXPHOS]], [[ETS]]).
:::: [[Image:P.jpg|link=OXPHOS capacity|OXPHOS]] [[Image:L.jpg|link=LEAK respiration|LEAK]] [[Image:E.jpg|link=ETS capacity|ET capacity]] In mitochondrial preparations, there are three well-defined coupling states of respiration, ''L'', ''P'', ''E'' ([[LEAK]], [[OXPHOS]], [[ET-pathway]]).
   
   
::: 1. If the [[metabolic control variable]], ''X'', is an [[uncoupler]], the reference state ''Z'' is ''E''. Then two [[background state]]s, ''Y'', of coupling control are possible: The uncoupler may act on the ''L'' or ''P'' state in mt-preparations. The corresponding coupling control factors are:  
::: 1. If the [[metabolic control variable]], ''X'', is an [[uncoupler]], the reference state ''Z'' is ''E''. Then two [[background state]]s, ''Y'', of coupling control are possible: The uncoupler may act on the ''L'' or ''P'' state in mt-preparations. The corresponding coupling control factors are:  
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::: 3. If the background state ''Y'' is ''L'', the metablic control variable from ''L'' to ''P'' is ADP saturated ATP turnover or release of an inhibitor of phosphorylation of ADP to ATP, and the reference state ''Z'' is ''E'', the coupling control factor is complex (compare 1 and 2):  
::: 3. If the background state ''Y'' is ''L'', the metablic control variable from ''L'' to ''P'' is ADP saturated ATP turnover or release of an inhibitor of phosphorylation of ADP to ATP, and the reference state ''Z'' is ''E'', the coupling control factor is complex (compare 1 and 2):  
::::* (''P-L'')/''E'' ('''phosphorylating respiration per ETS capacity''').
::::* (''P-L'')/''E'' ('''phosphorylating respiration per ET capacity''').




=== Intact cells ===
=== Intact cells ===
:::: [[Image:R.jpg|link=ROUTINE respiration|ROUTINE]] [[Image:L.jpg|link=LEAK respiration|LEAK]] [[Image:E.jpg|link=ETS capacity|ETS]] ''L<sub>Omy</sub>'' and ''E'' can be induced in intact cells, but state ''P'' cannot. However, the [[ROUTINE]] state of respiration, ''R'', can be measured in intact cells.  
:::: [[Image:R.jpg|link=ROUTINE respiration|ROUTINE]] [[Image:L.jpg|link=LEAK respiration|LEAK]] [[Image:E.jpg|link=ETS capacity|ET capacity]] ''L<sub>Omy</sub>'' and ''E'' can be induced in intact cells, but state ''P'' cannot. However, the [[ROUTINE]] state of respiration, ''R'', can be measured in intact cells.  


:::1. If the [[metabolic control variable]], ''X'', is an [[uncoupler]], the reference state ''Z'' is ''E''. Then two [[background state]]s, ''Y'', of coupling control are possible: The uncoupler may act on the ''L'' or ''R'' state in intact cells. The corresponding coupling control factors are:  
:::1. If the [[metabolic control variable]], ''X'', is an [[uncoupler]], the reference state ''Z'' is ''E''. Then two [[background state]]s, ''Y'', of coupling control are possible: The uncoupler may act on the ''L'' or ''R'' state in intact cells. The corresponding coupling control factors are:  
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:::3. If the background state ''Y'' is ''L'', the metablic control variable from ''L'' to ''R'' is cell controlled ATP turnover or release of an inhibitor of phosphorylation of ADP to ATP, and the reference state ''Z'' is ''E'', the coupling control factor is complex (compare 1 and 2):  
:::3. If the background state ''Y'' is ''L'', the metablic control variable from ''L'' to ''R'' is cell controlled ATP turnover or release of an inhibitor of phosphorylation of ADP to ATP, and the reference state ''Z'' is ''E'', the coupling control factor is complex (compare 1 and 2):  
::::* (''R-L'')/''E'' ('''ROUTINE phosphorylating respiration per ETS capacity''').
::::* (''R-L'')/''E'' ('''ROUTINE phosphorylating respiration per ET capacity''').





Revision as of 10:42, 20 October 2017


high-resolution terminology - matching measurements at high-resolution


Flux control efficiency

Description

Flux control factors express the control of respiration by a metabolic control variable, X, as a fractional change of flux from YX to ZX, normalized for ZX. ZX is the reference state with high (stimulated or un-inhibited) flux; YX is the background state at low flux, upon which X acts.

jX = (ZX-YX)/ZX = 1-YX/ZX

Complementary to the concept of flux control ratios and analogous to elasticities of metabolic control analysis, the flux control factor of X upon background YX is expressed as the change of flux from YX to ZX normalized for the reference state ZX. » MiPNet article

Abbreviation: FCF

Reference: Gnaiger 2014 MitoPathways


MitoPedia concepts: MiP concept, Respiratory control ratio, SUIT concept 


MitoPedia methods: Respirometry 

Flux control factor: normalization of mitochondrial respiration

Publications in the MiPMap
Gnaiger E (2014) Flux control factor: normalization of mitochondrial respiration. Mitochondr Physiol Network 2016-03-20; updated 2016-11-07.

» Gnaiger 2014 MitoPathways

OROBOROS (2016) MiPNet

Abstract: The flux control factor, FCF, and flux control ratio, FCR, are internal normalizations, expressing respiratory flux in a given state relative to respiratory flux in a reference state. Whereas FCRs express various respiratory states relative to a common refrence state, FCFs express the control of respiration in a step caused by a specific metabolic control variable, X. The concept of the FCF presents a generalized framework for assessing the effect of an experimental variable on flux and defines specific expressions, such as the biochemical coupling efficiency.


O2k-Network Lab: AT Innsbruck Gnaiger E


Labels: MiParea: Respiration 




Regulation: Flux control 


HRR: Theory 


Metabolic control variable and respiratory state

A metabolic control variable, X, is either added (stimulation, activation) or removed (reversal of inhibition) to yield a high flux in the reference state, Z, compared to the background state, Y. X denote the metabolic control variable (X), Y and Z are the respiratory states (Y, Z). To avoid introduction of multiple symbols, the same symbols are used to denote the corresponding respiratory fluxes, X=Z-Y. The FCF in step analysis relates to the change of flux caused by the single variable X. The FCR in state analysis compares fluxes in a variety of respiratory states which may be separated by single or multiple variables, i.e. separated by several coupling and [[pathway control state]s.
If inhibitors are experimentally added rather than removed (-X); then Y is the background state in the presence of the inhibitor.


Pathway control factor

Pathway control factors express the relative change of oxygen flux in response to a transition of (i) substrate availability or (ii) inhibitors of enzyme steps in the pathway, in a defined coupling state.
» NS-N pathway control factor, NS-S pathway control factor


Coupling control factor

Coupling control factors are determined in an ET-pathway competent state.

mt-Preparations

OXPHOS LEAK ET capacity In mitochondrial preparations, there are three well-defined coupling states of respiration, L, P, E (LEAK, OXPHOS, ET-pathway).
1. If the metabolic control variable, X, is an uncoupler, the reference state Z is E. Then two background states, Y, of coupling control are possible: The uncoupler may act on the L or P state in mt-preparations. The corresponding coupling control factors are:
2. If the metabolic control variable is stimulation by ADP, D, or release of an inhibitor of phosphorylation of ADP to ATP (DT-phosphorylation; e.g. -Omy), the reference state Z is P at saturating concentrations of ADP. The background state Y is L, and the corresponding coupling control factor is:
  • OXPHOS coupling efficiency, j≈P = (P-L)/P = 1-L/P (phosphorylating respiration per OXPHOS capacity, related to the respiratory acceptor control ratio, RCR). P-L or ≈P control factor.
3. If the background state Y is L, the metablic control variable from L to P is ADP saturated ATP turnover or release of an inhibitor of phosphorylation of ADP to ATP, and the reference state Z is E, the coupling control factor is complex (compare 1 and 2):
  • (P-L)/E (phosphorylating respiration per ET capacity).


Intact cells

ROUTINE LEAK ET capacity LOmy and E can be induced in intact cells, but state P cannot. However, the ROUTINE state of respiration, R, can be measured in intact cells.
1. If the metabolic control variable, X, is an uncoupler, the reference state Z is E. Then two background states, Y, of coupling control are possible: The uncoupler may act on the L or R state in intact cells. The corresponding coupling control factors are:
2. If the metabolic control variable is stimulation by ATP turnover or release of an inhibitor of phosphorylation of ADP to ATP (DT-phosphorylation; e.g. -Omy), the reference state Z is R in intact cells at physiologically controlled steady states of [ADP] and ATP-turnover. The background state Y is L, and the corresponding coupling control factor is:
3. If the background state Y is L, the metablic control variable from L to R is cell controlled ATP turnover or release of an inhibitor of phosphorylation of ADP to ATP, and the reference state Z is E, the coupling control factor is complex (compare 1 and 2):
  • (R-L)/E (ROUTINE phosphorylating respiration per ET capacity).


References