Description
Flux control efficiencies 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.
- jZ-Y = (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 efficiency of X upon background YX is expressed as the change of flux from YX to ZX normalized for the reference state ZX. Β» 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. |
Abstract: The flux control efficiency, jZ-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, jZ-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.
β’ 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. jZ-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.
- If inhibitors are experimentally added rather than removed (-X); then Y is the background rate in the presence of the inhibitor.
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.
- Β» 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, jE-L = (E-L)/E = 1-L/E (E-L coupling control efficiency).
- ET-excess coupling efficiency , jE-P = (E-P)/E = 1-P/E (E-P coupling control efficiency).
- 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:
- 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, jP-L = (P-L)/P = 1-L/P (P-L coupling control efficiency), related to the RCR.
- 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:
- 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).
- 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):
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, jE-L = (E-L)/E = 1-L/E (E-L coupling control efficiency).
- ET-reserve coupling efficiency, jE-R = (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 efficiencies 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 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, jR-L = (R-L)/R = 1-L/R (R-L coupling control efficiency).
- 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:
- 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).
- 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):
References
- Bioblast links: Normalization - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>
- Rate
- Β» Normalization of rate
- Β» Flow
- Β» Oxygen flow
- Β» Flux
- Β» Oxygen flux
- Β» Flux control ratio
- Β» Coupling-control ratio
- Β» Pathway control ratio
- Β» Flux control efficiency
- Rate
- Quantities for normalization
- Β» Count in contrast to Number
- Β» Mitochondrial marker
- Β» O2k-Protocols: mitochondrial and marker-enzymes
- Β» Citrate synthase activity
- Quantities for normalization
- General
- Β» Extensive quantity
- Β» Specific quantity
- Β» Advancement
- Β» Motive unit
- Β» Iconic symbols
- General
- Related keyword lists
MitoPedia concepts:
MiP concept,
Respiratory control ratio,
SUIT concept
MitoPedia methods:
Respirometry
Labels: MiParea: Respiration
Regulation: Flux control
HRR: Theory