Flux control factor

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Flux control factor

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.

ΔjX = (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, Δj≈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).


Living cells

ROUTINE LEAK ET-capacity L(Omy) and E can be induced in living cells, but state P cannot. However, the ROUTINE state of respiration, R, can be measured in living 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 living 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 living 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