Metabolite channeling: Implications for regulation of metabolism and for quantitative description of reactions in vivo

1991 ◽  
Vol 152 (1) ◽  
pp. 85-92 ◽  
Author(s):  
Michael A. Savageau
Keyword(s):  
Quantitative Description ◽  
Regulation Of Metabolism ◽  
Metabolite Channeling

scholarly journals Identification of the MuRF1 skeletal muscle ubiquitylome through quantitative proteomics

Function ◽  
2021 ◽  
Author(s):  
Leslie M Baehr ◽  
David C Hughes ◽  
Sarah A Lynch ◽  
Delphi Van Haver ◽  
Teresa Mendes Maia ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Potential Role ◽  
Ubiquitin Proteasome System ◽  
In Vivo Electroporation ◽  
Adult Mice ◽  
Expression Of Genes ◽  
Regulation Of Metabolism ◽  
Ubiquitin Proteasome

Abstract MuRF1 (TRIM63) is a muscle-specific E3 ubiquitin ligase and component of the ubiquitin proteasome system. MuRF1 is transcriptionally upregulated under conditions that cause muscle loss, in both rodents and humans, and is a recognized marker of muscle atrophy. In this study, we used in vivo electroporation to determine if MuRF1 overexpression alone can cause muscle atrophy and, in combination with ubiquitin proteomics, identify the endogenous MuRF1 substrates in skeletal muscle. Overexpression of MuRF1 in adult mice increases ubiquitination of myofibrillar and sarcoplasmic proteins, increases expression of genes associated with neuromuscular junction instability, and causes muscle atrophy. A total of 169 ubiquitination sites on 56 proteins were found to be regulated by MuRF1. MuRF1-mediated ubiquitination targeted both thick and thin filament contractile proteins, as well as, glycolytic enzymes, deubiquitinases, p62, and VCP. These data reveal a potential role for MuRF1 in not only the breakdown of the sarcomere, but also the regulation of metabolism and other proteolytic pathways in skeletal muscle.

Bioavailability in Vivo of Benzo[a]Pyrene Adsorbed to Diesel Particulate

1991 ◽  
Vol 7 (3) ◽  
pp. 125-139 ◽  
Author(s):  
David R. Bevan ◽  
David M. Ruggio
Keyword(s):  
Health Risks ◽  
Quantitative Description ◽  
Intratracheal Instillation ◽  
Direct Analysis ◽  
Sprague Dawley ◽  
Reasonable Estimate ◽  
Diesel Particulate ◽  
Sprague Dawley Rats

To evaluate health risks associated with exposure to particulates in the environment, it is necessary to quantify the bioavailability of carcinogens associated with the particulates. Direct analysis of bioavailability in vivo is most readily accomplished by adsorbing a radiolabeled form of the carcinogen to the particulate. A sam ple of native diesel particulate collected from an Oldsmobile die sel engine that contained 1.03 μ g benzo[ a] pyrene ( BaP)/ g particulate was supplemented with exogenous [ 3 H]- BaP to pro duce a particulate containing 2.62 μ g BaP/g. To insure that elu tion of BaP from native and [3 H] -BaP-supplemented particulate was similar, in vitro analyses were performed. When using phos pholipid vesicles composed of dimyristoylphosphatidylcholine (DMPC), 1.52% of total BaP was eluted from native particulate into the vesicles in 18 hrs; from [ 3 H] -BaP supplemented particu late, 1.68% was eluted. Using toluene as eluent, 2.55% was eluted from native particulate, and 8.25% from supplemented particulate, in 6 hrs. Supplemented particulate was then instilled intratracheally into male Sprague-Dawley rats and distribution of radioactivity was analyzed at selected times over 3 days. About 50% of radioactivity remained in lungs at 3 days following instil lation, with 30% being excreted into feces and the remainder dis tributed throughout the organs of the rats. To estimate the amount of radioactivity that entered feces through swallowing of a portion of the instilled dose, [3 H] -BaP-supplemented particu late was instilled intratracheally into rats that had a cannula sur gically implanted in the bile duct. Rate of elimination of radio activity into bile was monitored; 10.6% of radioactivity was re covered in 6 hr, an amount slightly lower than the 12.8% ex creted in 6 hrs into feces of animals with intact bile ducts. Our studies provide a quantitative description of the distribution of BaP and its metabolites following intratracheal instillation of diesel particulate. Because rates of elution of BaP in vitro are similar for native diesel particulate and particulate with supple mental [ 3H] -BaP, our results provide a reasonable estimate of the bioavailability in vivo of BaP associated with diesel particu late.

scholarly journals Regulation of Metabolism in Working Muscle in Vivo

1966 ◽  
Vol 241 (3) ◽  
pp. 632-634
Author(s):  
Bertram Sacktor ◽  
Edward C. Hurlbut
Keyword(s):  
Regulation Of Metabolism

Analysis of postcapillary pH changes in blood in vivo after gas exchange

1978 ◽  
Vol 44 (5) ◽  
pp. 770-781 ◽  
Author(s):  
A. Bidani ◽  
E. D. Crandall ◽  
R. E. Forster
Keyword(s):  
Gas Exchange ◽  
Time Course ◽  
Quantitative Description ◽  
Carbonic Anhydrase Activity ◽  
Transport Processes ◽  
Red Cell Membrane ◽  
Ph Changes ◽  
Pulmonary Capillaries ◽  
Dehydration Reactions

A quantitative description of the reaction and transport processes that take place in blood during and after gas exchange in capillaries is developed and used to interpret recently reported experimental results. Included in the computation are 1) CO2-H2CO3 hydration-dehydration reactions in plasma and erythrocytes, 2) CO2 reactions with hemoglobin, 3) O2 binding to hemoglobin, 4) buffering of H+ intra- and extracellularly, 5) HCO3- Cl- exchange across the red cell membrane, 6) diffusion of gases between alveolar gas and blood, and 7) transcellular movement of water. Ion and water fluxes are described assuming passive diffusion down their electrochemical potential gradients. Recent data on the magnitude of the Bohr and Haldane shifts and on carbamate formation in the presence of 2,3-diphosphoglycerate are used. The analysis is used to examine the direction, magnitude, and time course of plasma pH changes in blood leaving the pulmonary capillaries and is shown to preduct results that agree very closely with recently reported experimental measurements in vivo. The time computed for plasma pH equilibration after gas exchange when carbonic anhydrase activity is absent from plasma is so great that blood may never be in complete electrochemical equilibrium as it travels around the circulation in normal man.

A Mathematical Treatment of the Blood Dissociation Curve for Oxygen

1963 ◽  
Vol 9 (6) ◽  
pp. 745-762 ◽  
Author(s):  
Rodolfo Margaria
Keyword(s):  
Dissociation Constants ◽  
Quantitative Description ◽  
Mathematical Treatment ◽  
Physiological Effects ◽  
Functional Importance ◽  
Acidic Group ◽  
Oxygen Dissociation ◽  
Dissociation Curves

Abstract A quantitative description of Bohr's effect can be made from the oxygen dissociation curves of hemoglobin at different pHs, and the dissociation constants of the 02-linked acidic group of Hb (KR) and Hb02 (Ko) have been calculated as, respectively, 1.29 1O-8 and 3.42 10-7 at37°. On the assumption that the oxygenation of hemoglobin takes place in four successive steps, the constant for each equilibrium can easily be calculated, and the values given. It appears that the oxygenation takes place with the same affinity for the first three steps, while the affinity for the fourth oxygenation is 125 times greater. On the basis of these results a simplification of Adair's formula is given, containing only two constants, one (K) being representative of the affinity of the oxygen for the first three hemes, and the other (in)being the increase of affinity for the fourth oxygenation. This formula seems to fit most data in the literature of hemoglobin solutions and of blood in vivo and in vitro. The physiological effects and the functional importance of the increased affinity for the fourth oxygenation are described, and the possibility that disturbances of the Hb oxygenation process may be due to the lack of this process is considered.

Combining in vitro data and modelling to predict in vivo animal response

2006 ◽  
Vol 34 ◽  
pp. 135-144
Author(s):  
Jan Dijkstra ◽  
James France
Keyword(s):  
Quantitative Description ◽  
Gas Production ◽  
Biological Data ◽  
Mathematical Methods ◽  
Passage Rate ◽  
Fractional Rate ◽  
Microbial Efficiency ◽  
Definition Of

SummaryExisting feed evaluation systems for ruminants assess the feed value in a rather empirical way, with a limited ability to integrate metabolism in a meaningful framework. For the quantitative description of the mechanisms, appropriate biological data can be obtained using in vitro methods. The aim of this paper is to examine the use of modelling and in vitro data to predict digestion processes in vivo. Suitable mathematical methods are required to describe and interpret substrate disappearance profiles or gas production profiles. The derivation of such models is important since this allows a clear definition of the underlying assumptions made. Such assumptions are related to the change in fractional rate of degradation (kd) during incubation that will determine the shape of the profile. Furthermore, the value of the fractional passage rate (kp) is of crucial importance in the prediction of extent of degradation in the rumen. The development and application of models, based on classic microbial growth equations, clearly shows that observed variation in microbial efficiency in batch cultures (including the gas production technique) is not necessarily related to that in vivo. Rather, kp is again a major factor contributing to explanation of variation in microbial efficiency. Similarly, the end products of fermentation (VFA) and the VFA molar proportions can be estimated in vitro, but its direct applicability to the in vivo situation is limited. It is concluded that some potential uses of in vitro techniques are ultimately misleading. Mechanistic models indicate that mechanisms governing microbial efficiency and VFA molar proportions in vitro are not necessarily valid for the in vivo situation. Therefore, the in vitro data cannot be used directly for a uniform system of feed evaluation to predict animal responses. Rather, the in vitro data obtained for substrate degradation may be used in whole rumen models as a basal input value to indicate the degradation potential.

Automated Determination of the Magnitude and Time Delay (“Phase”) of the Cardiac Cycle Dependent Variation of Myocardial Ultrasonic Integrated Backscatter

1989 ◽  
Vol 11 (4) ◽  
pp. 245-259 ◽  
Author(s):  
G. A. Mohr ◽  
Zvi Vered ◽  
Benico Barzilai ◽  
Julio E. Perez ◽  
Burton E. Sobel ◽  
...  
Keyword(s):  
Time Delay ◽  
Tissue Characterization ◽  
Cardiac Cycle ◽  
Quantitative Description ◽  
Automated Analysis ◽  
Cyclic Variation ◽  
Integrated Backscatter ◽  
Automated Method ◽  
Cycle Dependent

An algorithm for quantitative description of cardiac cycle dependent variation of integrated backscatter (cyclic variation) has been developed and is shown to be suitable for analysis of nonsinusoidal data typical of ultrasonic tissue characterization measurements from myocardium in vivo. The algorithm produces estimates of the magnitude of variation and of the time delay relative to the the electrocardiographically recorded QRS-complex. To validate the algorithm, 246 integrated backscatter measurements were analyzed both manually and by the automated method. The magnitude and time delay estimates from the two methods correlated closely. With a separate set of data, the algorithm produced reasonable descriptions of the cyclic variation for 89 of 101 integrated backscatter measurements. Only modest computational power is required for effective implementation of this algorithm, facilitating inclusion of online automated analysis capabilities in quantitative ultrasonic tissue characterization systems.

scholarly journals Erythropoietin Signalling in Adipocytes is Not Essential for Regulation of Metabolism In Vivo

2013 ◽  
Vol 37 ◽  
pp. S67
Author(s):  
Cynthia T. Luk ◽  
Sally Y. Shi ◽  
Diana Choi ◽  
Erica P. Cai ◽  
Stephanie A. Schroer ◽  
...  
Keyword(s):  
Regulation Of Metabolism

Fidelity of the Estimation of the Deformation Gradient From Data Deduced From the Motion of Markers Placed on a Body That is Subject to an Inhomogeneous Deformation Field

2013 ◽  
Vol 135 (8) ◽  
Author(s):  
Vít Průša ◽  
K. R. Rajagopal ◽  
U. Saravanan
Keyword(s):  
Finite Number ◽  
Data Reduction ◽  
Deformation Gradient ◽  
Quantitative Description ◽  
The Body ◽  
Inhomogeneous Deformation ◽  
Actual Error ◽  
The Difference

Practically all experimental measurements related to the response of nonlinear bodies that are made within a purely mechanical context are concerned with inhomogeneous deformations, though, in many experiments, much effort is taken to engender homogeneous deformation fields. However, in experiments that are carried out in vivo, one cannot control the nature of the deformation. The quantity of interest is the deformation gradient and/or its invariants. The deformation gradient is estimated by tracking positions of a finite number of markers placed in the body. Any experimental data-reduction procedure based on tracking a finite number of markers will, for a general inhomogeneous deformation, introduce an error in the determination of the deformation gradient, even in the idealized case, when the positions of the markers are measured with no error. In our study, we are interested in a quantitative description of the difference between the true gradient and its estimate obtained by tracking the markers, that is, in the quantitative description of the induced error due to the data reduction. We derive a rigorous upper bound on the error, and we discuss what factors influence the error bound and the actual error itself. Finally, we illustrate the results by studying a practically interesting model problem. We show that different choices of the tracked markers can lead to substantially different estimates of the deformation gradient and its invariants. It is alarming that even qualitative features of the material under consideration, such as the incompressibility of the body, can be evaluated differently with different choices of the tracked markers. We also demonstrate that the derived error estimate can be used as a tool for choosing the appropriate marker set that leads to the deformation gradient estimate with the least guaranteed error.

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