Description
Flux control factors express the control of respiration by a metabolic 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
Gnaiger E (2014) Flux control factor: normalization of mitochondrial respiration. Mitochondr Physiol Network 2014-08-10. |
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.
- X: Metabolic control variable acting on the background state, Y, to yield the reference state, Z. X stimulates or un-inhibits Y from low flux to Z at high flux.
- Y: The background state is the non-activated or inhibited respiratory state at low flux in relation to the reference state, Z. A metabolic control variable, X, acts on Y (substrate, activator) or is removed from Y (inhibitor) to yield Z. The X-specific (in contrast to general) flux control ratio is jY = Y/Z.
- Z: The reference state, stimulated or un-inhibited by a metabolic control variable, X, with high flux in relation to the background state, Y.
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
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:
- E-L coupling control factor, jE-L = (E-L)/E = 1-L/E (biochemical coupling efficiency)
- Excess E-P capacity factor, ExP/E = (E-P)/E = 1-P/E (apparent ETS excess capacity factor over P)
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:
- P-L coupling control factor, jP-L = (P-L)/P = 1-L/P (phosphorylating respiration per OXPHOS capacity, related to the respiratory acceptor control ratio, RCR).
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
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:
- E-L coupling control factor, jE-L = (E-L)/E = 1-L/E (biochemical coupling efficiency).
- E-R coupling control factor, jE-P = (E-R)/E = 1-R/E (apparent ETS excess capacity over R).
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:
- R-L coupling control factor, jR-L = (R-L)/R = 1-L/R (ROUTINE coupling control factor).
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).