Difference between revisions of "Flux control efficiency"
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» [[Flux_control_factor#Flux_control_factor:_normalization_of_mitochondrial_respiration | '''MiPNet article''']] | » [[Flux_control_factor#Flux_control_factor:_normalization_of_mitochondrial_respiration | '''MiPNet article''']] | ||
|info=[[Gnaiger 2014 MitoPathways]] | |info=[[Gnaiger 2014 MitoPathways]] | ||
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|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 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. | ||
|mipnetlab=AT Innsbruck Gnaiger E | |mipnetlab=AT Innsbruck Gnaiger E | ||
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== Metabolic control variable and respiratory state == | == Metabolic control variable and respiratory state == | ||
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::::* [[Gnaiger 2015 Scand J Med Sci Sports]] | ::::* [[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.]] | ::::* [[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.]] | ||
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|mitopedia concept=MiP concept, Respiratory control ratio, SUIT concept | |||
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|mitopedia method=Respirometry | |||
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|area=Respiration | |||
|topics=Flux control | |||
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Revision as of 05:10, 18 May 2020
Description
Flux control factors express the control of respiration by a metabolic control variable, X, as a fractional change of flux from YX to ZX, normalized for ZX. ZX is the reference state with high (stimulated or un-inhibited) flux; YX is the background state at low flux, upon which X acts.
- ΔjX = (ZX-YX)/ZX = 1-YX/ZX
Complementary to the concept of flux control ratios and analogous to elasticities of metabolic control analysis, the flux control factor of X upon background YX is expressed as the change of flux from YX to ZX normalized for the reference state ZX. » MiPNet article
Abbreviation: FCF
Reference: Gnaiger 2014 MitoPathways
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. |
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
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 jY = 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.
- If inhibitors are experimentally added rather than removed (-X); then Y is the background state in the presence of the inhibitor.
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 ET-pathway competent state.
mt-Preparations
- In mitochondrial preparations, there are three well-defined coupling states of respiration, L, P, E (LEAK, OXPHOS, ET-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 factors are:
- Biochemical coupling efficiency, ΔjE-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.
- 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 factors are:
- 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:
- OXPHOS coupling efficiency, Δj≈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.
- 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:
- 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 ET-capacity).
- 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):
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 factors are:
- Biochemical coupling efficiency, ΔjE-L = (E-L)/E = 1-L/E (E-L coupling control factor).
- Excess E-R capacity factor, ΔjE-P = (E-R)/E = 1-R/E.
- 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 factors are:
- 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:
- ROUTINE coupling efficiency, ΔjR-L = (R-L)/R = 1-L/R (R-L or ≈R coupling control factor).
- 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:
- 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 ET-capacity).
- 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):
References
- Bioblast links: Normalization - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
- Quantities for normalization
- » Count in contrast to Number
- » Mitochondrial marker
- » O2k-Protocols: mitochondrial and marker-enzymes
- » Citrate synthase activity
- Quantities for normalization
- General
- Related keyword lists
MitoPedia concepts:
MiP concept,
Respiratory control ratio,
SUIT concept
MitoPedia methods:
Respirometry
Labels: MiParea: Respiration
Regulation: Flux control
HRR: Theory