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: MiP concept, Respiratory control ratio, SUIT concept 

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; 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.

• 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.

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 ETS-competent pathway control 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 2014 MitoPathways
• Gnaiger 2015 Scand J Med Sci Sports
• Biochemical coupling efficiency in permeabilized fibres from arm and leg muscle in Inuit versus Caucasians: A functional test of the uncoupling hypothesis in Greenland. Mitochondr Physiol Network 18.08.