Equilibrium enzymes in metabolic pathways

1996 ◽  
Vol 74 (3) ◽  
pp. 411-416 ◽  
Author(s):  
S. P. J. Brooks
Keyword(s):  
Steady State ◽  
Kinetic Parameters ◽  
Metabolic Pathways ◽  
Enzyme Locus ◽  
Steady State Flux ◽  
Equilibrium Reactions ◽  
Metabolic Sequence ◽  
Far From Equilibrium ◽  
Catalytic Capacity ◽  
Reaction Schemes

It is commonly believed that certain reactions in a metabolic sequence may be at or close to equilibrium because of the large excess of catalytic capacity compared to the flux through these enzyme loci. Simple algebraic manipulations can show that the equilibrium and steady state conditions are mutually exclusive. However, solution of the complete reaction schemes for model "equilibrium" reactions shows that they can remain far from equilibrium even though the ratio of enzyme flux to steady state flux through the overall pathway is high. These calculations show that a reaction's proximity to equilibrium depends on the overall flux through the enzyme locus as well as on the kinetic parameters of the other enzymes in the pathway. Thus, combinations of kinetic parameters may exist that allow certain reactions to approach equilibrium but these conditions are not universal.Key words: equilibria, theoretical kinetics, metabolic control.

scholarly journals Transient times in linear metabolic pathways under constant affinity constraints

1997 ◽  
Vol 327 (2) ◽  
pp. 493-498 ◽  
Author(s):  
Mónica LLORÉNS ◽  
C. Juan NUÑO ◽  
Francisco MONTERO
Keyword(s):  
Steady State ◽  
Metabolic Pathways ◽  
Analytical Study ◽  
Time Dependent ◽  
State Function ◽  
Transient Time ◽  
Input Flux ◽  
Linear Reaction ◽  
Transition Times ◽  
Reaction Schemes

In the early seventies, Easterby began the analytical study of transition times for linear reaction schemes [Easterby (1973) Biochim. Biophys. Acta 293, 552-558]. In this pioneer work and in subsequent papers, a state function (the transient time) was used to measure the period before the stationary state, for systems constrained to work under both constant and variable input flux, was reached. Despite the undoubted usefulness of this quantity to describe the time-dependent features of these kinds of systems, its application to the study of chemical reactions under other constraints is questionable. In the present work, a generalization of these magnitudes to linear metabolic pathways functioning under a constant-affinity constraint is carried out. It is proved that classical definitions of transient times do not reflect the actual properties of the transition to the steady state in systems evolving under this restriction. Alternatively, a more adequate framework for interpretation of the transient times for systems with both constant and variable input flux is suggested. Within this context, new definitions that reflect more accurately the transient characteristics of constant affinity systems are stated. Finally, the meaning of these transient times is discussed.

scholarly journals The effect of feedback on pathway transient response

1986 ◽  
Vol 233 (3) ◽  
pp. 871-875 ◽  
Author(s):  
J S Easterby
Keyword(s):  
Steady State ◽  
Metabolic Pathways ◽  
Transient Analysis ◽  
Steady States ◽  
Transient Time ◽  
Transient Behaviour ◽  
Steady State Flux ◽  
The Times ◽  
Time Required ◽  
State Functions

The effect of variation of the rate of input of material on the transient behaviour of metabolic pathways is examined. This reveals the existence of three transient times which make up the overall pathway transient. Two of these have been described previously and represent the times required for the accumulation of the free intermediate pool and the pool of enzyme-bound intermediate. They are state functions and as such are independent of the way in which the steady state was reached. The third is attributable to the variation in the rate of input of material to the pathway. It is dependent on three further factors. These are (a) the time required for the initial enzyme to reach its own steady state, (b) substrate depletion and (c) feedback. The description of the transient is: (Formula: see text) where V0 represents the rate of input and Vss represents the steady-state flux. The transient time associated with the transition between steady-states is shown to be a simple function of the transients for the establishment of each steady state from rest and may be expressed as: tau = tau b-Va/Vb . tau a where Va and Vb refer to the fluxes in the two steady states and tau a and tau b represent the transient times for the establishment of each of the steady-states from rest. The total pathway transient may now be completely defined as: (formula: see text) where summation over all intermediates, I, is implied. The significance of this to the analysis of pathway behaviour is discussed with more general examples of pathway transient analysis.

scholarly journals Steady state kinetic parameters for the thrombin-catalyzed conversion of human fibrinogen to fibrin.

1983 ◽  
Vol 258 (15) ◽  
pp. 9276-9282 ◽  
Author(s):  
D L Higgins ◽  
S D Lewis ◽  
J A Shafer
Keyword(s):  
Steady State ◽  
Kinetic Parameters ◽  
Human Fibrinogen ◽  
Steady State Kinetic ◽  
State Kinetic

scholarly journals Characterization of Nicotinamidases: Steady State Kinetic Parameters, Classwide Inhibition by Nicotinaldehydes, and Catalytic Mechanism

Biochemistry ◽  
2010 ◽  
Vol 49 (49) ◽  
pp. 10421-10439 ◽  
Author(s):  
Jarrod B. French ◽  
Yana Cen ◽  
Tracy L. Vrablik ◽  
Ping Xu ◽  
Eleanor Allen ◽  
...  
Keyword(s):  
Steady State ◽  
Kinetic Parameters ◽  
Catalytic Mechanism ◽  
Steady State Kinetic ◽  
State Kinetic

scholarly journals Variation in the Steady State Kinetic Parameters of Wild Type and Mutant T5 5′-3′-Exonuclease With pH

1999 ◽  
Vol 274 (25) ◽  
pp. 17711-17717 ◽  
Author(s):  
Timothy J. Pickering ◽  
Scott Garforth ◽  
Jon R. Sayers ◽  
Jane A. Grasby
Keyword(s):  
Steady State ◽  
Kinetic Parameters ◽  
Wild Type ◽  
Steady State Kinetic ◽  
State Kinetic

Estimation of kinetic parameters of androgen-synthesizing enzyme activities in superfused Leydig cells from rat testes: Difference between endogenous and exogenous substrates

1984 ◽  
Vol 4 (6) ◽  
pp. 483-488 ◽  
Author(s):  
Nikolaus Kühn-Velten ◽  
Joachim Wolff ◽  
Wolfgang Staib
Keyword(s):  
Steady State ◽  
Kinetic Parameters ◽  
Active Site ◽  
Enzyme Activities ◽  
Substrate Concentration ◽  
Leydig Cells ◽  
Hydroxysteroid Dehydrogenase ◽  
Endogenous Substrate ◽  
Catalyzed Reactions ◽  
Actual Substrate

Kinetic parameters of 3β-hydroxysteroid dehydrogenase/isomerase, steroid-17α-monooxygenase, and steroid-17,20-lyase activities were estimated under steady-state conditions. Purified Leydig cells from rat testes were superfused with pregnenolone, progesterone, or 17α-hydroxyprogesterone. The Km values for both the monooxygenase- and the lyase-catalyzed reactions were by factors of five to ten higher if analyzed with the exogenously added substrate (0.98 and 0.65 μM, respectively) than if calculated from endogenous substrate derived from a precursor (0.10 and 0.13 μM, respectively). This discrepancy may be explained by different substrate partition between the intra- and extraceIJular spaces and by different substrate concentration at the active site of the respective enzyme, depending on whether the actual substrate is of exogenous or endogenous source.

scholarly journals Improving the Antitumor Activity and Bioavailability of Sonidegib for the Treatment of Skin Cancer

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1560
Author(s):  
Amr Gamal ◽  
Haitham Saeed ◽  
Fatma I. Abo El-Ela ◽  
Heba F. Salem
Keyword(s):  
Steady State ◽  
Skin Cancer ◽  
Entrapment Efficiency ◽  
The United States ◽  
Relative Bioavailability ◽  
Passive Targeting ◽  
Therapeutic Benefits ◽  
Steady State Flux

Throughout the United States and the world, skin cancer is the most frequent form of cancer. Sonidegib (SNG) is a hedgehog inhibitor that has been used for skin cancer treatment. However, SNG has low bioavailability and is associated with resistance. The focus of this work is to enhance bioavailability, anti-tumor efficacy and targeting of SNG via developing ethosome gel as a potential treatment for skin cancer. SNG-loaded ethosomes formulation was prepared and characterized in vitro by %entrapment efficiency (%EE), vesicle size, morphology, %release and steady-state flux. The results showed that the prepared formulation was spherical nanovesicles with a %EE of 85.4 ± 0.57%, a particle size of 199.53 ± 4.51 nm and a steady-state flux of 5.58 ± 0.08 µg/cm2/h. In addition, SNG-loaded ethosomes formulation was incorporated into carbopol gel to study the anti-tumor efficacy, localization and bioavailability in vivo. Compared with oral SNG, the formulation showed 3.18 times higher relative bioavailability and consequently significant anti-tumor activity. In addition, this formulation showed a higher rate of SNG penetration in the skin’s deep layers and passive targeting in tumor cells. Briefly, SNG-loaded ethosome gel can produce desirable therapeutic benefits for treatment of skin cancer.

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