Cookies help us deliver our services. By using our services, you agree to our use of cookies. More information

Difference between revisions of "Flux control efficiency"

From Bioblast
Line 50: Line 50:
== Coupling control factor ==
== Coupling control factor ==


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


=== mt-Preparations ===
=== mt-Preparations ===

Revision as of 20:32, 7 November 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: 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.

Β» Gnaiger 2014 MitoPathways

OROBOROS (2016) MiPNet

Abstract: The flux control factor, FCF and flux control ratios, FCRs, are internal normalizations, expressing respiratory flux 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.


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 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 substrate and coupling states.
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 (Nwith 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 control 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