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Difference between revisions of "Flux control efficiency"

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= Flux control factor: normalization of mitochondrial respiration =

Revision as of 15:08, 8 February 2016


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 concepts: Respiratory state, Respiratory control ratio 


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 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