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Flux control efficiency

From Bioblast


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. Β» MiPNet article

Abbreviation: FCF

Reference: Gnaiger 2014 MitoPathways


MitoPedia methods: Respirometry 


MitoPedia topics: "Respiratory state" is not in the list (Enzyme, Medium, Inhibitor, Substrate and metabolite, Uncoupler, Sample preparation, Permeabilization agent, EAGLE, MitoGlobal Organizations, MitoGlobal Centres, ...) of allowed values for the "MitoPedia topic" property. Respiratory state"Respiratory state" is not in the list (Enzyme, Medium, Inhibitor, Substrate and metabolite, Uncoupler, Sample preparation, Permeabilization agent, EAGLE, MitoGlobal Organizations, MitoGlobal Centres, ...) of allowed values for the "MitoPedia topic" property., "Respiratory control ratio" is not in the list (Enzyme, Medium, Inhibitor, Substrate and metabolite, Uncoupler, Sample preparation, Permeabilization agent, EAGLE, MitoGlobal Organizations, MitoGlobal Centres, ...) of allowed values for the "MitoPedia topic" property. Respiratory control ratio"Respiratory control ratio" is not in the list (Enzyme, Medium, Inhibitor, Substrate and metabolite, Uncoupler, Sample preparation, Permeabilization agent, EAGLE, MitoGlobal Organizations, MitoGlobal Centres, ...) of allowed values for the "MitoPedia topic" property. 

Flux control factor: normalization of mitochondrial respiration

Publications in the MiPMap
Gnaiger E (2014) Flux control factor: normalization of mitochondrial respiration. Mitochondr Physiol Network 2014-08-10.

Β» Gnaiger 2014 MitoPathways

OROBOROS (2014) MiPNet

Abstract: The concept of flux control ratios is complemented by the flux control factor for normalization of respiration, which presents a generalized framework for assessing the effect of an experimental variable on flux and yields specific expressions, such as the biochemical coupling efficiency.


β€’ 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 thereference state, Z, from the background state, Y. X, Y and Z denote the metabolic control variable (X) or respiratory state (Y, Z) and the corresponding respiratory fluxes, X=Z-Y.

If inhibitors are experimentally added rather than removed (-X); then Y is the background state in the presence of the inhibitor.


Substrate control factor

Substrate control factors express the relative change of oxygen flux in response to a transition of substrate availability in a defined coupling state.

CI and CII are abbreviations for Complex I and Complex II, but indicate here CI-linked respiration (with pyruvate, glutamate, malate, or other ETS competent CI-linked substrate combinations) and CII-linked (with succinate) respiration. CI&II indicates respiration with a CI-and CII-linked substrate cocktail. The nomenclature using subscripts helps to distinguish CI+CII is the calculated sum of CI- plus CII-linked respiration measured separately, versus CI&II as the measured flux in the presence of a combination of CI- and CII-linked substrates.


Coupling control factor

Coupling control factors are determined in an ETS-competent substrate state.

mt-Preparations

OXPHOS LEAK ETS In mitochondrial preparations, there are three well-defined coupling states of respiration, L, P, E (LEAK, OXPHOS, ETS).

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, and on the L or R state in intact cells. The corresponding coupling control factors are:

2. If the metablic 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, jβ‰ˆP = (P-L)/P = 1-L/P (phosphorylating respiration per OXPHOS capacity, related to the respiratory acceptor control ratio, RCR). P-L or β‰ˆP 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 ETS capacity).


Intact cells

ROUTINE LEAK ETS 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 metablic 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 ETS capacity).


References