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
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:
- Biochemical coupling efficiency, jE-L = (E-L)/E = 1-L/E (E-L coupling control factor).
- Excess E-P capacity factor, ExP/E = (E-P)/E = 1-P/E.
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, jβP = (P-L)/P = 1-L/P (phosphorylating respiration per OXPHOS capacity, related to the respiratory acceptor control ratio, RCR). P-L or βP 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
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:
- Biochemical coupling efficiency, jE-L = (E-L)/E = 1-L/E (E-L coupling control factor).
- Excess E-R capacity factor, jE-P = (E-R)/E = 1-R/E.
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:
- ROUTINE coupling efficiency, jR-L = (R-L)/R = 1-L/R (R-L or βR 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).