Flux control efficiency

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Flux control efficiency

Description

Flux control capacities express the control of respiration by a metabolic variable, X, as a fractional change of flux from Y to Z, Δj (normalized for Z, dimensionless). Z is the reference state with high (stimulated or un-inhibited) flux; Y is the background state at low flux, upon which X acts. This yields the flux control ratio j_Y=Y/Z),

Δj_Z-Y = (Z-Y)/Z = 1-j_Y

Complementary to the concept of flux control ratios and analogous to elasticities of metabolic control analysis, the flux control capacity of X upon background Y is expressed as the change of flux from Y to Z normalized for the reference state Z.

Abbreviation: FCC

Reference: Gnaiger 2013 Abstract MiP2013

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. 

Gnaiger E (2013)

Flux control capacity. Bioblast-MitoPedia 2013-08-04.

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 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 capacity

Substrate control capacities express the relative change of oxygen flux in response to a transition of substrate availability in a defined coupling state.

• CII control capacity, CI control capacity

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- plus CII-linked substrate cocktail.

Coupling control capacity

Coupling control capacities 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 capacities are:

• E-L coupling control capacity, Δj_E-L = (E-L)/E = 1-L/E (biochemical coupling efficiency)
• E-P coupling control capacity, Δj_E-P = (E-P)/E = 1-P/E (apparent ETS excess capacity 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 capacity is:

• P-L coupling control capacity, Δj_P-L = (P-L)/P = 1-L/P (related to the respiratory acceptor control ratio, RCR)

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 capacities are:

• E-L coupling control capacity, Δj_E-L = (E-L)/E = 1-L/E (biochemical coupling efficiency)
• E-R coupling control capacity, Δj_E-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 capacitiy is:

• R-L coupling control capacity, Δj_R-L = (R-L)/R = 1-L/R (ROUTINE control capacity)