scholarly journals Increase in lysophosphatidate acyltransferase activity in oilseed rape ( Brassica napus ) increases seed triacylglycerol content despite its low intrinsic flux control coefficient

2019 ◽  
Vol 224 (2) ◽  
pp. 700-711
Author(s):  
Helen K. Woodfield ◽  
Stepan Fenyk ◽  
Emma Wallington ◽  
Ruth E. Bates ◽  
Alexander Brown ◽  
...  
Keyword(s):  
Brassica Napus ◽  
Oilseed Rape ◽  
Control Coefficient ◽  
Acyltransferase Activity ◽  
Flux Control ◽  
Flux Control Coefficient ◽  
Intrinsic Flux ◽  
Triacylglycerol Content

scholarly journals Evidence that the flux control coefficient of the respiratory chain is high during gluconeogenesis from lactate in hepatocytes from starved rats. Implications for the hormonal control of gluconeogenesis and action of hypoglycaemic agents

1987 ◽  
Vol 247 (2) ◽  
pp. 449-457 ◽  
Author(s):  
H J Pryor ◽  
J E Smyth ◽  
P T Quinlan ◽  
A P Halestrap
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Respiratory Chain ◽  
Glucose Production ◽  
Hormonal Control ◽  
Acid Oxidation ◽  
Control Coefficient ◽  
Atp Content ◽  
Flux Control ◽  
Flux Control Coefficient

1. Increasing concentrations of 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), a mild respiratory-chain inhibitor [Halestrap (1987) Biochim. Biophys. Acta 927, 280-290], caused progressive inhibition of glucose production from lactate + pyruvate by hepatocytes from starved rats incubated in the presence or absence of oleate and gluconeogenic hormones. 2. No significant changes in tissue ATP content were observed, but there were concomitant decreases in ketone-body output and cytochrome c reduction and increases in NADH fluorescence and the ratios of [lactate]/[pyruvate] and [beta-hydroxybutyrate]/[acetoacetate]. 3. The inhibition by DCMU of palmitoylcarnitine oxidation by isolated liver mitochondria was used to calculate a flux control coefficient of the respiratory chain towards gluconeogenesis. In the presence of 1 mM-oleate, the calculated values were 0.61, 0.39 and 0.25 in the absence of hormone and in the presence of glucagon or phenylephrine respectively, consistent with activation of the respiratory chain in situ as previously suggested [Quinlan & Halestrap (1986) Biochem. J. 236, 789-800]. 4. Cytoplasmic oxaloacetate concentrations were shown to decrease under these conditions, implying inhibition of pyruvate carboxylase. 5. Inhibition of gluconeogenesis from fructose and dihydroxyacetone was also observed with DCMU and was accompanied by an increased output of lactate + pyruvate, suggesting that activation of pyruvate kinase was occurring. With the latter substrate, measurements of tissue ADP and ATP contents showed that DCMU caused a small fall in [ATP]/[ADP] ratio. 6. Two inhibitors of fatty acid oxidation, pent-4-enoate and 2-tetradecylglycidate, were shown to abolish and to decrease respectively the effects of hormones, but not valinomycin, on gluconeogenesis from lactate + pyruvate, without changing tissue ATP content. 7. It is concluded that the hormonal increase in mitochondrial matrix volume stimulates fatty acid oxidation and respiratory-chain activity, allowing stimulation of pyruvate carboxylation and thus gluconeogenesis to occur without major changes in [ATP]/[ADP] or [NADH]/[NAD+] ratios. 8. The high flux control coefficient of the respiratory chain towards gluconeogenesis may account for the hypoglycaemic effect of mild respiratory-chain inhibitors.

Flux Control Coefficient

2013 ◽  
pp. 752-752
Author(s):  
Emma Saavedra ◽  
Rafael Moreno-Sánchez
Keyword(s):  
Control Coefficient ◽  
Flux Control ◽  
Flux Control Coefficient

scholarly journals The analysis of rate limitation within enzymes: relations between flux control coefficients of rate constants and unidirectional rates, rate constants and thermodynamic parameters of single isolated enzymes

1994 ◽  
Vol 300 (1) ◽  
pp. 159-164 ◽  
Author(s):  
G C Brown ◽  
C E Cooper
Keyword(s):  
Thermodynamic Parameters ◽  
Rate Constant ◽  
Rate Constants ◽  
Enzyme Mechanism ◽  
Control Coefficient ◽  
Flux Control ◽  
Flux Control Coefficient ◽  
Flux Control Coefficients ◽  
Measuring Control ◽  
Control Coefficients

The extent to which a rate constant or step within an enzyme mechanism limits the net enzyme rate in a particular condition can be quantified as a flux control coefficient. We derive here a number of relations between the control coefficients and the unidirectional rates, rate constants, and thermodynamic parameters of the enzyme. These and other relations are used to suggest a number of methods for experimentally measuring control coefficients within enzymes.

scholarly journals The importance of alcohol dehydrogenase in regulation of ethanol metabolism in rat liver cells

1991 ◽  
Vol 278 (3) ◽  
pp. 659-665 ◽  
Author(s):  
R A Page ◽  
K E Kitson ◽  
M J Hardman
Keyword(s):  
Alcohol Dehydrogenase ◽  
Competitive Inhibition ◽  
Rat Hepatocytes ◽  
Ethanol Metabolism ◽  
Control Coefficient ◽  
Flux Control ◽  
Irreversible Reaction ◽  
Flux Control Coefficient ◽  
Rate Determining Step ◽  
Rat Liver Cells

We used titration with the inhibitors tetramethylene sulphoxide and isobutyramide to assess quantitatively the importance of alcohol dehydrogenase in regulation of ethanol oxidation in rat hepatocytes. In hepatocytes isolated from starved rats the apparent Flux Control Coefficient (calculated assuming a single-substrate irreversible reaction with non-competitive inhibition) of alcohol dehydrogenase is 0.3-0.5. Adjustment of this coefficient to allow for alcohol dehydrogenase being a two-substrate reversible enzyme increases the value by 1.3-1.4-fold. The final value of the Flux Control Coefficient of 0.5-0.7 indicates that alcohol dehydrogenase is a major rate-determining enzyme, but that other factors also have a regulatory role. In hepatocytes from fed rats the Flux Control Coefficient for alcohol dehydrogenase decreases with increasing acetaldehyde concentration. This suggests that, as acetaldehyde concentrations rise, control of the pathway shifts from alcohol dehydrogenase to other enzymes, particularly aldehyde dehydrogenase. There is not a single rate-determining step for the ethanol metabolism pathway and control is shared among several steps.

scholarly journals Metabolic Control Analysis of Exponential Growth and Product Formation

2018 ◽  
Author(s):  
David Andrew Fell
Keyword(s):  
Steady State ◽  
Metabolic Control ◽  
Product Yield ◽  
Product Formation ◽  
Metabolic Control Analysis ◽  
Control Analysis ◽  
Control Coefficient ◽  
Flux Control ◽  
Flux Control Coefficient ◽  
Metabolic Fluxes

Metabolic Control Analysis defines the relationships between the change in activity of an enzyme and the resulting impacts on metabolic fluxes and metabolite concentrations at steady state. In many biotechnological applications of metabolic engineering, however, the goal is to alter the product yield. In this case, although metabolism may be at a pseudo-steady state, the amount of biomass catalysing the metabolism can be growing exponentially. Here, expressions are derived that relate the change in activity of an enzyme and its flux control coefficient to the change in yield from an exponentially growing system. Conversely, the expressions allow estimation of an enzyme's flux control coefficient over the pathway generating the product from measurements of the changes in enzyme activity and yield.

scholarly journals The flux control coefficient of carnitine palmitoyltransferase I on palmitate β-oxidation in rat hepatocyte cultures

1997 ◽  
Vol 323 (1) ◽  
pp. 119-122 ◽  
Author(s):  
Tracey D. SPURWAY ◽  
H. Stanley A. SHERRATT ◽  
Christopher I. POGSON ◽  
Loranne AGIUS
Keyword(s):  
Metabolic Control Analysis ◽  
Carnitine Palmitoyltransferase ◽  
Control Analysis ◽  
Control Coefficient ◽  
Irreversible Inhibitor ◽  
Rat Hepatocyte ◽  
Flux Control ◽  
Flux Control Coefficient ◽  
Carnitine Palmitoyltransferase I ◽  
Cpt I

Two important factors that determine the flux of hepatic β-oxidation of long-chain fatty acids are the availability of fatty acid and the activity of carnitine palmitoyltransferase I (CPT I). Using Metabolic Control Analysis, the flux control coefficient of CPT I in rat hepatocyte monolayers was determined by titration with 2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate (Etomoxir), which is converted to Etomoxir-CoA, an irreversible inhibitor of CPT I. We measured CPT I activity and flux through β-oxidation at 0.2 mM and 1.0 mM palmitate to simulate substrate concentrations in fed and fasted states. Rates of β-oxidation were 4.5-fold higher at 1.0 mM palmitate compared with 0.2 mM palmitate. Flux control coefficients of CPT I, estimated by two independent methods, were similar: 0.67 and 0.79 for 0.2 mM palmitate, and 0.68 and 0.77 for 1 mM palmitate. It is concluded that the regulatory potential of CPT I is similar at low and high physiological concentrations of palmitate.

scholarly journals Effects of thyroid hormone on mitochondrial oxidative phosphorylation

1985 ◽  
Vol 226 (1) ◽  
pp. 183-192 ◽  
Author(s):  
A J Verhoeven ◽  
P Kamer ◽  
A K Groen ◽  
J M Tager
Keyword(s):  
Thyroid Hormone ◽  
Oxidative Phosphorylation ◽  
Adenine Nucleotide ◽  
Hormone Treatment ◽  
Adenine Nucleotide Translocator ◽  
Control Coefficient ◽  
Bc1 Complex ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Flux Control ◽  
Flux Control Coefficient

In order to locate sites of action of thyroid hormone on mitochondrial oxidative phosphorylation we have used an experimental application of control analysis as previously described [Groen, Wanders, Westerhoff, Van der Meer & Tager (1982) J. Biol. Chem. 257, 2754-2757]. Rat-liver mitochondria were isolated from hypothyroid rats or from hypothyroid rats 24 h after treatment with a single dose of 3,3′,5-triiodothyronine (T3). The amount of control exerted by four different steps on State-3 respiration with succinate as respiratory substrate was quantified by using specific inhibitors. The hormone treatment resulted in an increase in the flux control coefficient of the adenine nucleotide translocator, the dicarboxylate carrier and cytochrome c oxidase and a decrease in the flux control coefficient of the bc1-complex. The results of this analysis indicate that thyroid hormone treatment results in an activation of the bc1-complex and of at least one other enzyme, possibly succinate dehydrogenase. Measurement of the extramitochondrial ATP/ADP ratio at different rates of respiration (induced by addition of different amounts of hexokinase in the presence of glucose and ATP) showed that the adenine nucleotide translocator operates at a higher (ATP/ADP)out after T3 treatment, which supports previous reports on stimulation of this step by thyroid hormone.

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