Flux control efficiency

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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 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. » MiPNet article

Abbreviation: jZ-Y

Reference: Gnaiger 2020 BEC MitoPathways

Flux control efficiency: normalization of mitochondrial respiration

Publications in the MiPMap
Gnaiger E (2020) Flux control efficiency: normalization of mitochondrial respiration. Mitochondr Physiol Network 2016-03-20; updated 2020-11-10.

» Gnaiger 2020 BEC MitoPathways

Oroboros (2020) MiPNet

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 single 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 Z in the reference state, compared to flux Y in the background state. 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 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 states.
If inhibitors are experimentally added rather than removed (-X); then YX is the background rate in the presence of the inhibitor.
  • X: Metabolic control variable acting on YX in the background state, to yield rate ZX in the reference state. X stimulates or un-inhibits YX from low flux to ZX at high flux.
  • YX: The rate in the background state Y is the non-activated or inhibited respiratory rate (low) in relation to the high rate ZX in the reference state Z. A metabolic control variable, X, acts on YX (substrate, activator) or is removed from Y (inhibitor) to yield ZX. The X-specific (in contrast to general) flux control ratio is Y/Z.
  • ZX: The rate in the reference state Z, stimulated or un-inhibited by a metabolic control variable, X, with high rate in relation to rate YX 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


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

OXPHOS LEAK ET capacity In mitochondrial preparations, there are three well-defined coupling states of respiration, L, P, E (LEAK respiration, OXPHOS, Electron transfer pathway).
1. If the metabolic control variable, X, is an uncoupler, the reference rate ZX is E. Then two background states Y, of coupling control are possible: The uncoupler may act on L or P in mt-preparations. The corresponding flux 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 rate Z is P at saturating concentrations of ADP. The background rate Y is L, and the corresponding flux control efficiency is:
3. If the background rate 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 ratio is expressed as the net P/E control ratio (compare 1 and 2):
  • (P-L)/E


Living cells

ROUTINE LEAK ET capacity L(Omy) and E can be induced in living cells, but rate P cannot. However, the ROUTINE rate of respiration R can be measured in living cells.
1. If the metabolic control variable X is an uncoupler, the reference rate Z is E. Then two background states, Y of coupling control are possible: The uncoupler may act on the LEAK respiration or ROUTINE 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 flux 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 ratio is expressed as the net R/E control ratio (compare 1 and 2):
  • (R-L)/E


References


Keywords

  • Expand Bioblast links to Flux control efficiency


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Mitochondrial and cellular respiratory rates in coupling-control states

OXPHOS-coupled energy cycles. Source: The Blue Book
» Baseline state
Respiratory rate Definition Icon
OXPHOS capacity P = -Rox P.jpg mt-preparations
ROUTINE respiration R = -Rox R.jpg living cells
ET capacity E = -Rox E.jpg » Level flow
» Noncoupled respiration - Uncoupler
LEAK respiration L = -Rox L.jpg » Static head
» LEAK state with ATP
» LEAK state with oligomycin
» LEAK state without adenylates
Residual oxygen consumption Rox L = -Rox ROX.jpg
  • Chance and Williams nomenclature: respiratory states
» State 1 —» State 2 —» State 3 —» State 4 —» State 5

Flux control ratios related to coupling in mt-preparations and living cells

» Flux control ratio
» Coupling-control ratio
» Coupling-control protocol
FCR Definition Icon
L/P coupling-control ratio L/P L/P coupling-control ratio » Respiratory acceptor control ratio, RCR = P/L
L/R coupling-control ratio L/R L/R coupling-control ratio
L/E coupling-control ratio L/E L/E coupling-control ratio » Uncoupling-control ratio, UCR = E/L
P/E control ratio P/E P/E control ratio
R/E control ratio R/E R/E control ratio
net P/E control ratio (P-L)/E net P/E control ratio
net R/E control ratio (R-L)/E net R/E control ratio

Net, excess, and reserve capacities of respiration

Respiratory net rate Definition Icon
P-L net OXPHOS capacity P-L P-L net OXPHOS  capacity
R-L net ROUTINE capacity R-L R-L net ROUTINE capacity
E-L net ET capacity E-L E-L net ET capacity
E-P excess capacity E-P E-P excess capacity
E-R reserve capacity E-R E-R reserve capacity

Flux control efficiencies related to coupling-control ratios

» Flux control efficiency jZ-Y
» Background state
» Reference state
» Metabolic control variable
Coupling-control efficiency Definition Icon Canonical term
P-L control efficiency jP-L = (P-L)/P = 1-L/P P-L control efficiency P-L OXPHOS-flux control efficiency
R-L control efficiency jR-L = (R-L)/R = 1-L/R R-L control efficiency R-L ROUTINE-flux control efficiency
E-L coupling efficiency jE-L = (E-L)/E = 1-L/E E-L coupling efficiency E-L ET-coupling efficiency » Biochemical coupling efficiency
E-P control efficiency jE-P = (E-P)/E = 1-P/E E-P control efficiency E-P ET-excess flux control efficiency
E-R control efficiency jE-R = (E-R)/E = 1-R/E E-R control efficiency E-R ET-reserve flux control efficiency

General

» Basal respiration
» Cell ergometry
» Dyscoupled respiration
» Dyscoupling
» Electron leak
» Electron-transfer-pathway state
» Hyphenation
» Oxidative phosphorylation
» Oxygen flow
» Oxygen flux
» Permeabilized cells
» Phosphorylation system
» Proton leak
» Proton slip
» Respiratory state
» Uncoupling



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


MitoPedia methods: Respirometry 


Labels: MiParea: Respiration 




Regulation: Flux control 


HRR: Theory