scholarly journals Urolithiasis associated with atazanavir may mask a metabolic 'channelling' bias

2013 ◽  
Vol 69 (1) ◽  
pp. 284-285 ◽  
Author(s):  
G. Guaraldi ◽  
G. Dolci ◽  
A. Bellasi
Keyword(s):  
Metabolic Channelling

Control theory of metabolic channelling

1994 ◽  
pp. 313-331
Author(s):  
Boris N. Kholodenko ◽  
Marta Cascante ◽  
Hans V. Westerhoff
Keyword(s):  
Control Theory ◽  
Metabolic Channelling

scholarly journals Strong control on the transit time in metabolic channelling

FEBS Letters ◽  
1996 ◽  
Vol 389 (2) ◽  
pp. 123-125 ◽  
Author(s):  
Boris N. Kholodenko ◽  
Naoto Sakamoto ◽  
Joaquim Puigjaner ◽  
Hans V. Westerhoff ◽  
Marta Cascante
Keyword(s):  
Transit Time ◽  
Metabolic Channelling ◽  
Strong Control

Control theory of metabolic channelling

1994 ◽  
Vol 133-134 (1) ◽  
pp. 313-331 ◽  
Author(s):  
Boris N. Kholodenko ◽  
Marta Cascante ◽  
Hans V. Westerhoff
Keyword(s):  
Control Theory ◽  
Metabolic Channelling

scholarly journals [14C]bicarbonate fixation into glucose and other metabolites in the liver of the starved rat under halothane anaesthesia. Metabolic channelling of mitochondrial oxaloacetate

1985 ◽  
Vol 227 (3) ◽  
pp. 851-865 ◽  
Author(s):  
D F Heath ◽  
J G Rose
Keyword(s):  
Pyruvate Carboxylase ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Co2 Exchange ◽  
Published Data ◽  
Citrate Cycle ◽  
Incomplete Mixing ◽  
Metabolic Channelling ◽  
Glucose Output

Previous attempts to account for the labelling in vivo of liver metabolites associated with the citrate cycle and gluconeogenesis have foundered because proper allowance was not made for the heterogeneity of the liver. In the basal state (anaesthetized after 24h starvation) this heterogeneity is minimal, and we show that labelling by [14C]bicarbonate can be interpreted unambiguously. [14C]Bicarbonate was infused to an isotopic steady state, and measurements were made of specific radioactivities of blood bicarbonate, alanine, glycerol and lactate, of liver alanine and lactate, and of individual carbon atoms in blood glucose and liver aspartate, citrate and malate. (Existing methods for several of these measurements were extensively modified.) The results were combined with published rates of gluconeogenesis, uptake of gluconeogenic precursors by the liver, and citrate-cycle flux, all measured under similar conditions, and with estimates of other rates made from published data. To interpret the results, three ancillary measurements were made: the rate of CO2 exchange by phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) under conditions that simulated those in vivo; the 14C isotope effect in the pyruvate carboxylase (EC 6.4.1.1) reaction (14C/12C = 0.992 +/- 0.008; S.E.M., n = 8); the ratio of labelling by [2-14C]- to that by [1-14C]-pyruvate of liver glutamate 1.5 min after injection. This ratio, 3.38, is a measure of the disequilibrium in the mitochondria between malate and oxaloacetate. The data were analysed with due regard to experimental variance, uncertainties in values of fluxes measured in vitro, hepatic heterogeneity and renal glucose output. The following conclusions were reached. The results could not be explained if CO2 fixation was confined to pyruvate carboxylase and there was only one, well-mixed, pool of oxaloacetate in the mitochondria. Addition of the other carboxylation reactions, those of PEPCK, isocitrate dehydrogenase (EC 1.1.1.42) and malic enzyme (EC 1.1.1.40), was not enough. Incomplete mixing of mitochondrial oxaloacetate had to be assumed, i.e. that there was metabolic channelling of oxaloacetate formed from pyruvate towards gluconeogenesis. There was some evidence that malate exchange across the mitochondrial membrane might also be channelled, with incomplete mixing with that in the citrate cycle. Calculated rates of exchange of CO2 by PEPCK were in agreement with those measured in vitro, with little or no activation by Fe2+ ions.(ABSTRACT TRUNCATED AT 400 WORDS)

scholarly journals Effect of channelling on the concentration of bulk-phase intermediates as cytosolic proteins become more concentrated

1996 ◽  
Vol 313 (3) ◽  
pp. 921-926 ◽  
Author(s):  
Boris N. KHOLODENKO ◽  
Hans V. WESTERHOFF ◽  
CASCANTE CASCANTE
Keyword(s):  
Protein Concentration ◽  
Equilibrium Constants ◽  
Pool Size ◽  
Bulk Phase ◽  
Cytosolic Proteins ◽  
Metabolic Channelling ◽  
Proportional Increase ◽  
Hit And Run ◽  
Dynamic Channel ◽  
State Concentration

This paper shows that metabolic channelling can provide a mechanism for decreasing the concentration of metabolites in the cytoplasm when cytosolic proteins become more concentrated. A metabolic pathway in which two sequential enzymes can form a dynamic complex catalysing the direct transfer of an intermediate is compared with the analogous pathway lacking a channel (an ‘ideal’ pathway). In an ideal pathway a proportional increase in protein content does not result in a change in the steady-state concentration of the bulk-phase intermediate, whereas in a channelling pathway the bulk-phase intermediate either decreases or increases depending on the elemental rate constants within the enzyme mechanisms. When the concentrations of the enzymes are equal, the pool size decreases with increasing protein concentration if the elemental step depleting the bulk-phase intermediate exerts more control on its concentration than the step supplying the intermediate. Results are illustrated numerically, and a simplified dynamic channel is analysed in which the concentration of the enzyme–enzyme complex is negligible compared with the monomeric enzyme forms. For such a ‘hit-and-run’ channel it is shown that, when the product-releasing step of the enzyme located upstream is close to equilibrium, the pool size decreases as the concentrations of the enzymes increase in proportion, regardless of the rate, equilibrium constants and concentration ratios of the two sequential enzymes.

scholarly journals Bean and Pea Plastoglobules Change in Response to Chilling Stress

2021 ◽  
Vol 22 (21) ◽  
pp. 11895
Author(s):  
Joanna Wójtowicz ◽  
Joanna Grzyb ◽  
Joanna Szach ◽  
Radosław Mazur ◽  
Katarzyna B. Gieczewska
Keyword(s):  
Plant Species ◽  
High Performance ◽  
Chilling Stress ◽  
Spatial Proximity ◽  
Force Microscopy ◽  
Stage Of Development ◽  
Atomic Force ◽  
Metabolic Channelling ◽  
Transmission Electron ◽  
Insight Into

Plastoglobules (PGs) might be characterised as microdomains of the thylakoid membrane that serve as a platform to recruit proteins and metabolites in their spatial proximity in order to facilitate metabolic channelling or signal transduction. This study provides new insight into changes in PGs isolated from two plant species with different responses to chilling stress, namely chilling-tolerant pea (Pisum sativum) and chilling-sensitive bean (Phaseolus coccineus). Using multiple analytical methods, such as high-performance liquid chromatography and visualisation techniques including transmission electron microscopy and atomic force microscopy, we determined changes in PGs’ biochemical and biophysical characteristics as a function of chilling stress. Some of the observed alterations occurred in both studied plant species, such as increased particle size and plastoquinone-9 content, while others were more typical of a particular type of response to chilling stress. Additionally, PGs of first green leaves were examined to highlight differences at this stage of development. Observed changes appear to be a dynamic response to the demands of photosynthetic membranes under stress conditions.

Metabolic channelling of carbamoyl phosphate in the hyperthermophilic archaeon Pyrococcus furiosus: dynamic enzyme–enzyme interactions involved in the formation of the channelling complex

2004 ◽  
Vol 32 (2) ◽  
pp. 306-309 ◽  
Author(s):  
J. Massant ◽  
N. Glansdorff
Keyword(s):  
Protein Interactions ◽  
Pyrococcus Furiosus ◽  
Hyperthermophilic Archaea ◽  
Physical Interaction ◽  
Protein Protein Interactions ◽  
Carbamoyl Phosphate ◽  
Molecular Physiology ◽  
Metabolic Channelling ◽  
Aspartate Carbamoyltransferase ◽  
Carbamate Kinase

Protection of thermolabile metabolites and coenzymes is a somewhat neglected but essential aspect of the molecular physiology of hyperthermophiles. Detailed information about the mechanisms used by thermophiles to protect these thermolabile metabolites and coenzymes is still scarce. A case in point is CP (carbamoyl phosphate), a precursor of pyrimidines and arginine, which is an extremely labile and potentially toxic intermediate. Recently we obtained the first evidence for a physical interaction between two hyperthermophilic enzymes for which kinetic evidence had suggested that these enzymes channel a highly thermolabile and potentially toxic intermediate. By physically interacting with each other, CKase (carbamate kinase) and OTCase (ornithine carbamoyltransferase) prevent thermodenaturation of CP in the aqueous cytoplasmic environment. The CP channelling complex involving CKase and OTCase or ATCase (aspartate carbamoyltransferase), identified in hyperthermophilic archaea, provides a good model system to investigate the mechanism of metabolic channelling and the molecular basis of protein–protein interactions in the physiology of extreme thermophiles.

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