Metabolism of totally ischemic excised dog heart I. Construction of a computer model

1979 ◽  
Vol 237 (5) ◽  
pp. R318-R326 ◽  
Author(s):  
Murray J. Achs ◽  
David Garfinkel
Keyword(s):  
Computer Model ◽  
Metabolic Regulation ◽  
Krebs Cycle ◽  
The Body ◽  
Heavy Sedation ◽  
Dog Heart ◽  
Rat Hearts ◽  
Heart Preparation ◽  
Time Courses ◽  
Underlying Mechanisms

Construction and fit to the experimental data of a computer model of glycolysis, the Krebs cycle, and related metabolism in an ischemic dog heart preparation, involving 122 metabolites, 65 enzymes, and 406 chemical reactions, is described. The experimental preparation simulated is a dog heart excised from the body, placed in a beaker of Tyrode's solution, and sampled for 100 min; the model required only moderate modification from models representing perfused rat hearts, and little modification from a model of another ischemic dog heart preparation. Common underlying mechanisms for the ischemia are indicated, although this preparation appears to evolve more slowly with time, perhaps owing to heavy sedation and diffusion-limited transport. Lactate is, at first, exported and then accumulates intracellularly; pH falls, but not as much in the mitochondria as the cytoplasm; redox couples go reduced, but with counterintuitive time courses; calcium phosphate is calculated to precipitate, as often observed in cardiac ischemia enzymes; glycolysis; simulation; metabolic regulation Submitted on October 24, 1978 Accepted on May 21, 1979

Metabolism of the acutely ischemic dog heart. I. Construction of a computer model

1979 ◽  
Vol 236 (1) ◽  
pp. R21-R30
Author(s):  
M. J. Achs ◽  
D. Garfinkel
Keyword(s):  
Computer Model ◽  
Experimental Error ◽  
Krebs Cycle ◽  
Pyridine Nucleotides ◽  
Dog Heart ◽  
Glycolytic Intermediates ◽  
Metabolic Difference ◽  
Principal Change ◽  
Underlying Mechanisms ◽  
Large Animals

Construction of a computer model of glycolysis, the Krebs cycle, and related metabolism in acutely ischemic dog heart, involving 122 metabolites, 65 enzymes, and 406 chemical reactions, is described. A previous model of the same metabolism in normal-flow rat heart was modified to fit ischemic dog heart experimental data to within experimental error. The result resembles other models of ischemic heart preparations, implying common underlying mechanisms. The principal change made was reduction of enzyme amounts, consistent with the generally slower metabolism of large animals, suggesting that differing enzyme amounts are a major component of interspecies metabolic difference. Glycolytic intermediates oscillate, asynchronously and with large changes in level; pyridine nucleotides become highly reduced; pH falls, but mitochondria stay alkaline relative to cytoplasm even after oxidative phosphorylation stops.

scholarly journals Physiology and Physical Chemistry of Bile Acids

2021 ◽  
Vol 22 (4) ◽  
pp. 1780
Author(s):  
Maria Chiara di Gregorio ◽  
Jacopo Cautela ◽  
Luciano Galantini
Keyword(s):  
Physical Chemistry ◽  
Bile Acids ◽  
Material Science ◽  
Metabolic Regulation ◽  
Enterohepatic Circulation ◽  
Building Blocks ◽  
The Body ◽  
Active Molecule ◽  
Supramolecular Aggregates ◽  
Biological Field

Bile acids (BAs) are facial amphiphiles synthesized in the body of all vertebrates. They undergo the enterohepatic circulation: they are produced in the liver, stored in the gallbladder, released in the intestine, taken into the bloodstream and lastly re-absorbed in the liver. During this pathway, BAs are modified in their molecular structure by the action of enzymes and bacteria. Such transformations allow them to acquire the chemical–physical properties needed for fulling several activities including metabolic regulation, antimicrobial functions and solubilization of lipids in digestion. The versatility of BAs in the physiological functions has inspired their use in many bio-applications, making them important tools for active molecule delivery, metabolic disease treatments and emulsification processes in food and drug industries. Moreover, moving over the borders of the biological field, BAs have been largely investigated as building blocks for the construction of supramolecular aggregates having peculiar structural, mechanical, chemical and optical properties. The review starts with a biological analysis of the BAs functions before progressively switching to a general overview of BAs in pharmacology and medicine applications. Lastly the focus moves to the BAs use in material science.

scholarly journals PPARs as Metabolic Sensors and Therapeutic Targets in Liver Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8298
Author(s):  
Hugo Christian Monroy-Ramirez ◽  
Marina Galicia-Moreno ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Arturo Santos ◽  
...  
Keyword(s):  
Liver Diseases ◽  
Metabolic Regulation ◽  
Structural Changes ◽  
Critical Role ◽  
The Body ◽  
Molecular Characteristics ◽  
Signal Pathways ◽  
Virus Infections ◽  
Physiological Processes ◽  
Hepatic Level

Carbohydrates and lipids are two components of the diet that provide the necessary energy to carry out various physiological processes to help maintain homeostasis in the body. However, when the metabolism of both biomolecules is altered, development of various liver diseases takes place; such as metabolic-associated fatty liver diseases (MAFLD), hepatitis B and C virus infections, alcoholic liver disease (ALD), and in more severe cases, hepatocelular carcinoma (HCC). On the other hand, PPARs are a family of ligand-dependent transcription factors with an important role in the regulation of metabolic processes to hepatic level as well as in other organs. After interaction with specific ligands, PPARs are translocated to the nucleus, undergoing structural changes to regulate gene transcription involved in lipid metabolism, adipogenesis, inflammation and metabolic homeostasis. This review aims to provide updated data about PPARs’ critical role in liver metabolic regulation, and their involvement triggering the genesis of several liver diseases. Information is provided about their molecular characteristics, cell signal pathways, and the main pharmacological therapies that modulate their function, currently engaged in the clinic scenario, or in pharmacological development.

STATE OF AUTONOMIC REGULATION OF HEART RHYTHM IN YOUNG AND AGED RATS BEFORE AND AFTER APPLICATION OF DIFFERENT REGIMENS OF RHYTHMIC EXTREME COOLING

2020 ◽  
pp. 436-443
Author(s):  
В. В. Кулик ◽  
В. Г. Бабийчук
Keyword(s):  
Heart Rate ◽  
Metabolic Regulation ◽  
Experimental Studies ◽  
Autonomic Regulation ◽  
The Body ◽  
Total Power ◽  
Aged Rats ◽  
Cooling Mode ◽  
Adaptive Capabilities ◽  
Extreme Cold

В работе изучено влияние разных режимов ритмических экстремальных холодовых воздействий на состояние вегетативной регуляции сердечного ритма у молодых и старых крыс. По данным спектрального анализа вариабельности сердечного ритма установлено, что у молодых крыс использование температурных режимов ритмических экстремальных холодовых воздействий, РЭХВ (-120 °С; -120 °С; -120 °С) и (-60 °С; -120 °С; -120 °С) значительно повышало адаптационные возможности организма за счет активации собственных гомеостатических регуляторных систем. При этом комбинированный режим РЭХВ (-60 °С; -120 °С; -120 °С) оказался наиболее оптимальным для старых животных, поскольку его применение не сопровождалось чрезмерной активацией симпатико-адреналовой системы на ранних этапах экспериментальных исследований в отличие от режима (-120 °С; -120 °С; -120 °С). Кроме того, использование данного режима охлаждения способствовало статистически значимому увеличению показателей общей мощности спектра нейрогуморальной регуляции не столько за счет повышения активности гуморально-метаболического звена регуляции, преобладание которого характерно для пожилого возраста, сколько благодаря увеличению тонуса вегетативных центров, причем парасимпатические влияния на миокард превалировали над симпатическими. The influence of various rhythmic extreme cold effects on the state of autonomic regulation of heart rate in young and aged rats was studied. According to the spectral analysis of heart rate variability, it has been found that in young rats, using rhythmic extreme cold exposures (RECE) temperature regimens of (-120 °С; -120 °С; -120 °С) and (-60 °С; -120 °С; -120 °С) significantly increased adaptive capabilities of the body due to the activation of its own homeostatic regulatory systems. At the same time, the combined regimen of RECE (-60 °С; -120 °С; -120 °С) occurred to be the most optimal for aged animals, since its use was not accompanied with an excessive activation of sympathoadrenal system at the early stages of experimental studies, in contrast to the regimen (-120 °С; -120 °С; -120 °С). In addition, the use of this cooling mode contributed to a statistically significant increase in the total power of spectrum of neurohumoral regulation not so much due to a rise in activity of humoral-metabolic regulation link, the prevalence of which is characteristic of an old age, but due to an increase in the tone of vegetative centers, herewith the parasympathetic effects on the myocardium prevailed sympathetic ones.

ATP depletion and mitochondrial functional loss during ischemia in slow and fast heart-rate hearts

1990 ◽  
Vol 259 (6) ◽  
pp. H1759-H1766 ◽  
Author(s):  
W. Rouslin ◽  
C. W. Broge ◽  
I. L. Grupp
Keyword(s):  
Mitochondrial Function ◽  
Atp Depletion ◽  
Mitochondrial Atpase ◽  
Small Contribution ◽  
Bicarbonate Buffer ◽  
Tissue Ph ◽  
Atp Production ◽  
Dog Heart ◽  
Rat Hearts

In the present study, isolated dog and rat hearts were perfused in the Langendorff mode with Krebs bicarbonate buffer in the absence and presence of 10(-5) M oligomycin. The perfusion protocols employed allowed tissue pH to drop during subsequent ischemic incubations essentially as it would in blood-perfused hearts. Tissue pH, ATP, lactate, and mitochondrial respiratory function were measured during the course of subsequent zero-flow ischemic incubations. The adenosinetriphosphatase (ATPase) activities attributable to both mitochondrial and nonmitochondrial ATPases in sonicated heart homogenates and the actomyosin ATPase in isolated cardiac myofibrils were measured in both species. Consistent with earlier results with a different model in which tissue pH was buffered during the ischemic incubations [W. Rouslin, J. L. Erickson, and R. J. Solaro. Am. J. Physiol. 250 (Heart Circ. Physiol. 19): H503-H508, 1986], the inhibition of the mitochondrial ATPase in situ by oligomycin markedly slowed both tissue ATP depletion and the loss of mitochondrial function during ischemia in the dog. However, oligomycin had only a very small and transient effect on ATP depletion and mitochondrial function in the rat. This was apparently so because of the fivefold higher rate of glycolytic ATP production as well as the nearly threefold higher total nonmitochondrial ATPase activity of ischemic rat compared with ischemic dog heart. These results suggest that although the inhibition of the mitochondrial ATPase makes a major contribution to ATP conservation in ischemic dog heart, it makes only a very small contribution in rat.

scholarly journals Macrophages as Emerging Key Players in Mitochondrial Transfers

2021 ◽  
Vol 9 ◽  
Author(s):  
Yidan Pang ◽  
Changqing Zhang ◽  
Junjie Gao
Keyword(s):  
Cardiovascular Diseases ◽  
Metabolic Regulation ◽  
Inflammatory Diseases ◽  
Negative Influence ◽  
Immune Defense ◽  
The Body ◽  
Key Players ◽  
Current Therapies ◽  
Obesity And Cancer ◽  
Host Tissues

Macrophages are a group of heterogeneous cells widely present throughout the body. Under the influence of their specific environments, via both contact and noncontact signals, macrophages integrate into host tissues and contribute to their development and the functions of their constituent cells. Mitochondria are essential organelles that perform intercellular transfers to regulate cell homeostasis. Our review focuses on newly discovered roles of mitochondrial transfers between macrophages and surrounding cells and summarizes emerging functions of macrophages in transmitophagy, metabolic regulation, and immune defense. We also discuss the negative influence of mitochondrial transfers on macrophages, as well as current therapies targeting mitochondria in macrophages. Regulation of macrophages through mitochondrial transfers between macrophages and their surrounding cells is a promising therapy for various diseases, including cardiovascular diseases, inflammatory diseases, obesity, and cancer.

scholarly journals The effects of sweeteners and sweetness enhancers on obesity and diabetes: a review

2018 ◽  
Vol 4 ◽  
Author(s):  
Yanli Jiao ◽  
Yu Wang
Keyword(s):  
Metabolic Regulation ◽  
Hormone Secretion ◽  
Taste Receptor ◽  
Caloric Intake ◽  
Sweet Taste ◽  
The Body ◽  
Incretin Hormone ◽  
Obesity And Diabetes ◽  
Sweet Taste Receptors

Sweet taste, one of the five basic taste qualities, is not only important for evaluation of food quality, but also guides the dietary food choices of animals. Sweet taste involves a variety of chemical compounds and structures, including natural sugars, sugar alcohols, natural and artificial sweeteners, and sweet-tasting proteins. The preference for sweetness has induced the over-consumption of sugar, contributing to certain prevailing health problems, such as obesity, diabetes and cardiovascular disease. Non-nutritive sweeteners, including natural and synthetic sweeteners, and sweet-tasting proteins have been added to foods to reduce the caloric intake from sugar, but many of these sugar substitutes induce an off-taste or after taste that negatively impacts any pleasure derived from the sweet taste. Sweet taste is detected by sweet taste receptor, that also play an important role in the metabolic regulation of the body, such as glucose homeostasis and incretin hormone secretion. In this review, the role of sweet tastants and the sweet taste receptors involved in sweetness perception, and their effect on obesity and diabetes are summarized. Sweet taste enhancement, as a new way to solve the over-consumption of sugar, is discussed in this contribution. Sweet taste enhancers can bind with sweet tastans to potentiate the sweetness of food without producing any taste by itself. Various type of sweet taste enhancers, including synthetic compounds, food-processed substances and aroma compounds, are summarized. Notably, few natural, non-volatile compounds have been identified as sweetness enhancers.

Abstract 3560: Use of Hyperpolarized Magnetic Resonance for Non-Invasive Observation of Metabolic Regulation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Marie A Schroeder ◽  
Lisa C Heather ◽  
Helen J Atherton ◽  
Kieran Clarke ◽  
George K Radda ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Metabolic Regulation ◽  
Krebs Cycle ◽  
Enzyme Regulation ◽  
Product Inhibition ◽  
Acetyl Coa ◽  
Fed State ◽  
Fasted Rats ◽  
Pyruvate Ratio

Hyperpolarized magnetic resonance (HP MR) has enabled real time visualization of in vivo metabolism. In this study, we postulated that HP MR could also non-invasively provide a measure of metabolic regulation. We focused on regulation of pyruvate dehydrogenase (PDH), a highly controlled enzyme that catalyzes the oxidation of pyruvate to acetyl CoA and CO2/HCO3-. We compared PDH flux in conditions of normal and attenuated enzyme activity, and in the presence of normal and augmented Krebs cycle flux, to determine the contributions of PDH activity and end product inhibition to enzyme regulation. Six rats were examined in the fed and fasted states (to modulate PDH activity), with 40 μmol HP 13C1-pyruvate alone and 40 μmol HP pyruvate co-infused with 40 μmol malate (to manipulate Krebs cycle flux/acetyl CoA uptake). HP tracer was infused into the rats in an MR scanner and cardiac spectra were acquired every second for 1 min. Conversion of pyruvate to 13HCO3-was monitored and the 13HCO3-/pyruvate ratio was used as a marker of PDH flux. Infusion of malate increased PDH flux by 31% compared with pyruvate alone, indicating that removal of acetyl CoA by incorporation into the Krebs cycle increased PDH flux. PDH flux was 57% lower in fasted rats injected with pyruvate alone compared with fed rats, and did not change with malate co-infusion. Here, low PDH activity prevented additional enzyme flux. These results suggest that end product inhibition limits fed state PDH flux, whereas PDH activity regulates pyruvate oxidation in the fasted state. In conclusion, this study has provided evidence that HP MR may be useful to obtain details of metabolic regulation, rather than just reflecting metabolic state. Figure 1 Bicarbonate/pyruvate ratio in fed and fasted rats, following an injection of pyruate or pyruate plus malate. In fed rats, co-infusion of malate increased PDH flux by 31% compared with injection of pyruvate alone (*p=0.02). Fasting reduced PDH flux by 57% (**p=0.002) following injection of pyruvate alone. Co-infusion with malate did not affect PDH flux in fasted rats.

Biophysical Insight into Protein Folding, Aggregate Formation and its Inhibition Strategies

2021 ◽  
Vol 28 ◽  
Author(s):  
Syed Mohammad Zakariya ◽  
Aiman Zehr ◽  
Rizwan Hasan Khan
Keyword(s):  
Protein Folding ◽  
Amyloid Fibrils ◽  
Three Dimensional ◽  
The Body ◽  
Aggregate Formation ◽  
Structural Characterisation ◽  
Current Scenario ◽  
Underlying Mechanisms ◽  
Quality Control Mechanism ◽  
Insight Into

: The failure of protein to correctly fold into its functional and unique three dimensional form leads to misfolded or partially folded protein. When these rogue proteins and polypeptides escape the quality control mechanism within the body, they result in aberrant aggregation of proteins into characteristic amyloid fibrils. This is the main cause for the number of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s and Huntington’s diseases. This review aims to summarise the underlying mechanisms of protein folding, misfolding and aggregation. It also highlights the recent technologies for the structural characterisation and detection of amyloid fibrils in addition to the various factors responsible for the aggregate formation and the strategies to combat the aggregation process. Besides, the journey from origin to the current scenario of protein aggregation is also concisely discussed.

Cellular metabolism

2021 ◽  
pp. 105-194
Keyword(s):  
Electron Transport Chain ◽  
Inborn Errors Of Metabolism ◽  
Krebs Cycle ◽  
Cellular Metabolism ◽  
Atp Synthesis ◽  
The Body ◽  
Clinical Aspects ◽  
Inborn Errors ◽  
Transport Chain ◽  
Cellular Compartments

‘Cellular metabolism’ addresses the major biochemical pathways and processes of the cells of the body. These include the central metabolic pathways involved in energy production: the tricarboxylic acid or Krebs cycle, and ATP synthesis through the electron transport chain and oxidative phosphorylation (chemiosmotic theory). Metabolism of each of the major fuel sources is considered: lipids, carbohydrates, and proteins, including energy storage as fat and glycogen, and excretion of nitrogen via the urea cycle. The different cellular compartments for metabolism are explored, as is the integration and regulation of the metabolic processes in a number of conditions such as fasting and starvation, exercise, pregnancy, and diabetes. Finally in this chapter the clinical aspects of metabolism are discussed, including energy balance and nutrition, obesity, and inborn errors of metabolism.

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