Description

Flux control efficiencies 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_Z-Y = (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 efficiency 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

Flux control efficiency: normalization of mitochondrial respiration

Gnaiger E (2020) Flux control efficiency: normalization of mitochondrial respiration. Mitochondr Physiol Network 2016-03-20; updated 2020-11-07.

» Gnaiger 2020 MitoPathways

Oroboros (2020) MiPNet

Abstract: The flux control efficiency, j_Z-Y, 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, j_Z-Y express the control of respiration in a step caused by a specific metabolic control variable, X. The concept of the flux control efficiency 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

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 denotes the metabolic control variable, Y and Z are the respiratory states, whereas Y and Z denote the corresponding respiratory fluxes. j_Z-Y 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 rate in the presence of the inhibitor.

X: Metabolic control variable acting on Y in the background state, to yield rate Z in the reference state. X stimulates or un-inhibits Y from low flux to Z at high flux.
Y: The rate in the background state Y is the non-activated or inhibited respiratory rate (low) in relation to the high rate Z in 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 Y/Z.
Z: The rate in the reference state Z, stimulated or un-inhibited by a metabolic control variable, X, with high rate in relation to rate Y in the background state Y.

Pathway control efficiency

Pathway control efficiencies express the relative change of oxygen flux in response to a transition of (1) CHNO-fuel substrates or (2) inhibitors of enzyme steps in the pathway, in a defined coupling state.

» NS-N pathway control efficiency, NS-S pathway control efficiency

Coupling control efficiency

Coupling control efficiencies are determined in an ET-pathway competent state. The terms coupling efficiency and coupling control efficiency are used synonymously.

mt-Preparations

In mitochondrial preparations, there are three well-defined coupling states of respiration, L, P, E (LEAK, OXPHOS, Electron transfer 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 efficiencies are:

ET-coupling efficiency, j_E-L = (E-L)/E = 1-L/E (E-L coupling control efficiency).
ET-excess coupling efficiency , j_E-P = (E-P)/E = 1-P/E (E-P coupling control efficiency).

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 efficiency is:

OXPHOS-coupling efficiency, j_P-L = (P-L)/P = 1-L/P (P-L coupling control efficiency), related to the 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 rate Z is E, the coupling control efficiency is complex (compare 1 and 2):

(P-L)/E (net OXPHOS-control ratio).

Living cells

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 efficiencies are:

ET-coupling efficiency, j_E-L = (E-L)/E = 1-L/E (E-L coupling control efficiency).
ET-reserve coupling efficiency, j_E-R = (E-R)/E = 1-R/E.

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 rate Z is R in living cells at physiologically controlled steady states of [ADP] and ATP-turnover. The background rate Y is L, and the corresponding coupling control efficiency is:

ROUTINE coupling efficiency, j_R-L = (R-L)/R = 1-L/R (R-L coupling control efficiency).

3. If the background rate 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 rate Z is E, the coupling control efficiency is complex (compare 1 and 2):