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Flux control efficiency

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):

(R-L)/E (net ROUTINE-control ratio).

References

Bioblast links: Normalization - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>

Rate

» Normalization of rate

» Flow

» Oxygen flow

» Flux

» Oxygen flux

» Flux control ratio

» Coupling-control ratio

» Pathway control ratio

» Flux control efficiency

Quantities for normalization

» Count in contrast to Number

» Mitochondrial marker

» O2k-Protocols: mitochondrial and marker-enzymes

» Citrate synthase activity

General

» Extensive quantity

» Specific quantity

» Advancement

» Motive unit

» Iconic symbols

Related keyword lists

» Keywords: Concentration and pressure

MitoPedia concepts: MiP concept, Respiratory control ratio, SUIT concept

MitoPedia methods: Respirometry

Labels: MiParea: Respiration

Regulation: Flux control

HRR: Theory

@@ Line 1: / Line 1: @@
 {{MitoPedia
 |abbr=''FCF''
-|description='''Flux control factors''' express the control of respiration by a [[metabolic control variable]], ''X'', as a fractional change of flux from ''Y<sub>X</sub>'' to ''Z<sub>X</sub>'', normalized for ''Z<sub>X</sub>''. ''Z<sub>X</sub>'' is the [[reference state]] with high (stimulated or un-inhibited) flux; ''Y<sub>X</sub>'' is the [[background state]] at low flux, upon which ''X'' acts.
+|description='''Flux control efficiencies''' express the control of respiration by a [[metabolic control variable]], ''X'', as a fractional change of flux from ''Y<sub>X</sub>'' to ''Z<sub>X</sub>'', normalized for ''Z<sub>X</sub>''. ''Z<sub>X</sub>'' is the [[reference state]] with high (stimulated or un-inhibited) flux; ''Y<sub>X</sub>'' is the [[background state]] at low flux, upon which ''X'' acts.
-:: Δ''j<sub>X</sub>'' = (''Z<sub>X</sub>-Y<sub>X</sub>'')/''Z<sub>X</sub>'' = 1-''Y<sub>X</sub>''/''Z<sub>X</sub>''
+:: ''j<sub>Z-Y</sub>'' = (''Z<sub>X</sub>-Y<sub>X</sub>'')/''Z<sub>X</sub>'' = 1-''Y<sub>X</sub>''/''Z<sub>X</sub>''
-Complementary to the concept of [[flux control ratio]]s and analogous to [[elasticity|elasticities]] of [[metabolic control analysis]], the flux control factor of ''X'' upon background ''Y<sub>X</sub>'' is expressed as the change of flux from ''Y<sub>X</sub>'' to ''Z<sub>X</sub>'' normalized for the reference state ''Z<sub>X</sub>''.
+Complementary to the concept of [[flux control ratio]]s and analogous to [[elasticity|elasticities]] of [[metabolic control analysis]], the flux control efficiency of ''X'' upon background ''Y<sub>X</sub>'' is expressed as the change of flux from ''Y<sub>X</sub>'' to ''Z<sub>X</sub>'' normalized for the reference state ''Z<sub>X</sub>''.
-» [[Flux_control_factor#Flux_control_factor:_normalization_of_mitochondrial_respiration | '''MiPNet article''']]
+» [[Flux_control_efficiency#Flux_control_efficiency:_normalization_of_mitochondrial_respiration | '''MiPNet article''']]
 |info=[[Gnaiger 2014 MitoPathways]]
 }}
 __TOC__
-= Flux control factor: normalization of mitochondrial respiration =
+= Flux control efficiency: normalization of mitochondrial respiration =
 {{Publication
-|title=Gnaiger E (2014) Flux control factor: normalization of mitochondrial respiration. Mitochondr Physiol Network 2016-03-20; updated 2016-11-07.
+|title=Gnaiger E (2020) Flux control efficiency: normalization of mitochondrial respiration. Mitochondr Physiol Network 2016-03-20; updated 2020-11-07.
-|info=[[Gnaiger 2014 MitoPathways]]
+|info=[[Gnaiger 2020 MitoPathways]]
 |authors=Oroboros
-|year=2016
+|year=2020
 |journal=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 ''FCR''s express various respiratory states relative to a common refrence state, ''FCF''s 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.
+|abstract=The [[flux control efficiency]], ''j<sub>Z-Y</sub>'', and [[flux control ratio]], ''FCR'', are internal normalizations, expressing respiratory flux in a given state relative to respiratory flux in a reference state. Whereas ''FCR''s express various respiratory states relative to a common refrence state, ''j<sub>Z-Y</sub>'' 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.
 |mipnetlab=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'' 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-control state |coupling]] and [[pathway control state]s.
+:::: 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<sub>Z-Y</sub>'' 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-control state |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.
+:::: 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 the [[background state]], ''Y'', to yield the [[reference state]], ''Z''. ''X'' stimulates or un-inhibits ''Y'' from low flux to ''Z'' at high flux.
+::::* ''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 '''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<sub>Y</sub>'' = ''Y/Z''.
+::::* ''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 '''reference state''', stimulated or un-inhibited by a [[metabolic control variable]], ''X'', with high flux in relation to the [[background state]], ''Y''.
+::::* ''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 factor ==
+== Pathway control efficiency ==
-:::: [[Pathway control factor]]s 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.
+:::: [[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 factor]], [[NS-S pathway control factor]]
+::::» [[NS-N pathway control efficiency]], [[NS-S pathway control efficiency]]
-== Coupling control factor ==
+== Coupling control efficiency ==
-:::: [[Coupling control factor]]s are determined in an [[ET-pathway competent state]].
+:::: [[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 ===
 :::: [[Image:P.jpg|link=OXPHOS capacity|OXPHOS]] [[Image:L.jpg|link=LEAK respiration|LEAK]] [[Image:E.jpg|link=ET capacity|ET capacity]] 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 state]]s, ''Y'', of coupling control are possible: The uncoupler may act on the ''L'' or ''P'' state in mt-preparations. The corresponding coupling control factors are:
+::: 1. If the [[metabolic control variable]], ''X'', is an [[uncoupler]], the reference state ''Z'' is ''E''. Then two [[background state]]s, ''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:
-::::* [[Biochemical coupling efficiency]], Δ''j<sub>E-L</sub>'' = (''E-L'')/''E'' = 1-''L/E'' (''E-L'' coupling control factor).
+::::* [[ET-coupling efficiency]], ''j<sub>E-L</sub>'' = (''E-L'')/''E'' = 1-''L/E'' (''E-L'' coupling control efficiency).
-::::* [[Excess E-P capacity factor |Excess ''E-P'' capacity factor]], ''ExP/E'' = (''E-P'')/''E'' = 1-''P/E''.
+::::* [[ET-excess coupling efficiency ]], ''j<sub>E-P</sub>'' = (''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 factor is:
+::: 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]], Δ''j<sub>≈P</sub>'' = (''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.
+::::* [[OXPHOS-coupling efficiency]], ''j<sub>P-L</sub>'' = (''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 state ''Z'' is ''E'', the coupling control factor is complex (compare 1 and 2):
+::: 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'' ('''phosphorylating respiration per ET capacity''').
+::::* (''P-L'')/''E''  ('''net OXPHOS-control ratio''').
@@ Line 57: / Line 57: @@
 :::: [[Image:R.jpg|link=ROUTINE respiration|ROUTINE]] [[Image:L.jpg|link=LEAK respiration|LEAK]] [[Image:E.jpg|link=ET capacity|ET capacity]] ''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 state]]s, ''Y'', of coupling control are possible: The uncoupler may act on the ''L'' or ''R'' state in living cells. The corresponding coupling control factors are:
+:::1. If the [[metabolic control variable]], ''X'', is an [[uncoupler]], the reference state ''Z'' is ''E''. Then two [[background state]]s, ''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:
-::::* [[Biochemical coupling efficiency]], Δ''j<sub>E-L</sub>'' = (''E-L'')/''E'' = 1-''L/E'' (''E-L'' coupling control factor).
+::::* [[ET-coupling efficiency]], ''j<sub>E-L</sub>'' = (''E-L'')/''E'' = 1-''L/E'' (''E-L'' coupling control efficiency).
-::::* [[Excess E-R capacity factor |Excess ''E-R'' capacity factor]], Δ''j<sub>E-P</sub>'' = (''E-R'')/''E'' = 1-''R/E''.
+::::* [[ET-reserve coupling efficiency]], ''j<sub>E-R</sub>'' = (''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 state ''Z'' is ''R'' in living cells at physiologically controlled steady states of [ADP] and ATP-turnover. The background state ''Y'' is ''L'', and the corresponding coupling control factor is:
+:::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]], Δ''j<sub>R-L</sub>'' = (''R-L'')/''R'' = 1-''L/R'' (''R-L'' or ''≈R'' coupling control factor).
+::::* [[ROUTINE coupling efficiency]], ''j<sub>R-L</sub>'' = (''R-L'')/''R'' = 1-''L/R'' (''R-L'' coupling control efficiency).
-:::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):
+:::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):
-::::* (''R-L'')/''E'' ('''ROUTINE phosphorylating respiration per ET capacity''').
+::::* (''R-L'')/''E'' ('''net ROUTINE-control ratio''').
 == References ==
-::::* [[Gnaiger 2014 MitoPathways]]
+::::* [[Gnaiger 2020 MitoPathways]]
 ::::* [[Gnaiger 2015 Scand J Med Sci Sports]]
 ::::* [[Gnaiger 2013 Abstract MiP2013|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.]]

Difference between revisions of "Flux control efficiency"