Difference between revisions of "Flux control efficiency"
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::: 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 factor 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]], 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. | ||
::: 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 state ''Z'' is ''E'', the coupling control factor is complex (compare 1 and 2): |
Revision as of 14:35, 3 June 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, 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 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