Flux control efficiency

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 Y_X to Z_X, normalized for Z_X. Z_X is the reference state with high (stimulated or un-inhibited) flux; Y_X is the background state at low flux, upon which X acts.

j_X = (Z_X-Y_X)/Z_X = 1-Y_X/Z_X

Complementary to the concept of flux control ratios and analogous to elasticities of metabolic control analysis, the flux control factor of X upon background Y_X is expressed as the change of flux from Y_X to Z_X normalized for the reference state Z_X. » MiPNet article

Abbreviation: FCF

Reference: Gnaiger 2014 MitoPathways

MitoPedia concepts: Respiratory state, Respiratory control ratio, "MitoFit Quality Control System" is not in the list (MiP concept, Respiratory state, Respiratory control ratio, SUIT concept, SUIT protocol, SUIT A, SUIT B, SUIT C, SUIT state, Recommended, ...) of allowed values for the "MitoPedia concept" property. MitoFit Quality Control System"MitoFit Quality Control System" 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. 

MitoPedia methods: Respirometry 

Flux control factor: normalization of mitochondrial respiration

Gnaiger E (2014) Flux control factor: normalization of mitochondrial respiration. Mitochondr Physiol Network 2016-03-20.

» 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.

• 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.

• 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 j_Y = 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.

• CII control factor, CI control factor

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 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, j_E-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, j_≈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 ETS capacity).

Intact cells

L_Omy 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, j_E-L = (E-L)/E = 1-L/E (E-L coupling control factor).
• Excess E-R capacity factor, j_E-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, j_R-L = (R-L)/R = 1-L/R (R-L or ≈R 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).

References

• Gnaiger 2015 Scand J Med Sci Sports