Mechanism Of Energy Production Research Articles

Impaired oxygen kinetics in beta‐thalassaemia major patients

Beta-thalassaemia major (TM) affects oxygen flow and utilization and reduces patients' exercise capacity. The aim of this study was to assess phase I and phase II oxygen kinetics during submaximal exercise test in thalassaemics and make possible considerations about the pathophysiology of the energy-producing mechanisms and their expected exercise limitation. Twelve TM patients with no clinical evidence of cardiac or respiratory disease and 10 healthy subjects performed incremental, symptom-limited cardiopulmonary exercise testing (CPET) and submaximal, constant workload CPET. Oxygen uptake (VO2), carbon dioxide output and ventilation were measured breath-by-breath. Peak VO2 was reduced in TM patients (22.3 +/- 7.4 vs. 28.8 +/- 4.8 mL kg(-1) min(-1), P < 0.05) as was anaerobic threshold (13.1 +/- 2.7 vs. 17.4 +/- 2.6 mL kg(-1) min(-1), P = 0.002). There was no difference in oxygen cost of work at peak exercise (11.7 +/- 1.9 vs. 12.6 +/- 1.9 mL min(-1) W(-1) for patients and controls respectively, P = ns). Phase I duration was similar in TM patients and controls (24.6 +/- 7.3 vs. 23.3 +/- 6.6 s respectively, P = ns) whereas phase II time constant in patients was significantly prolonged (42.8 +/- 12.0 vs. 32.0 +/- 9.8 s, P < 0.05). TM patients present prolonged phase II on-transient oxygen kinetics during submaximal, constant workload exercise, compared with healthy controls, possibly suggesting a slower rate of high energy phosphate production and utilization and reduced oxidative capacity of myocytes; the latter could also account for their significantly limited exercise tolerance.

Nanomechanics = biomechanics

Nanomechanics = biomechanicsThe knowledge of the mechanism of mechanical energy production by the so-called bioengines, living cells, could be very helpful for resolving different tasks concerning nanomechanics, e.g., construction of nanorobots. The present work considers a new idea, namely that the conformational changes within the so-called track, actin filament or microtubule are crucial for production of the mechanical energy by all bioengines. This concept contrasts with the presently prevailing view, according to which the force is generated as a result of conformational changes within the so-called motor proteins: myosin, kinesin or dynein.

Mitochondrial transcription factors, Tfam and Tfb2 m regulate the SERCA2 gene transcription. A coordinate regulatory mechanism of energy production and expenditure

Background: The heart consumes ATP, which is mainly produced in mitochondria. Mitochondrial enzymes are produced under the control of mitochondrial specific transcription factor, Tfam and its enhancer, Tfb2 m. SERCA2 plays a central role in cardiac function by using ATP. Therefore, we tested if Tfam and Tfb2 m activate SERCA2 gene transcription as well as mitochondrial gene in the normal and diseased heart. Results: Localization of Tfam/Tfb2 m in the nucleus was demonstrated by immunostaining. ChIP assay revealed Tfam and Tfb2 m bound to the −479 to −1nt region of the SERCA2 gene promoter. Fluorescence correlation spectroscopy further revealed Tfam and Tfb2 m bound to the −122 to −114nt and the −122 to −117nt region, respectively. Overexpression of Tfam and Tfb2 m increased the SERCA2 gene transcription by 96% and their ablation diminished the SERCA2 transcription by 65 %. In the rat myocardial infarction model, SERCA2 mRNA level was significantly correlated with Tfam(r = 0.52, p < 0.001) and Tfb2m(r = 0.72, p < 0.001) mRNA. In the neonatal rat cultured myocytes, mutation of either Tfam or Tfb2 m binding sites decreased basal SERCA2 luciferase activity. Norepinephrine, an inducer of heart failure, decreased SERCA2 luciferase activity and its effect was further enhanced when mutations were induced. Conclusion: Our study revealed a novel machanism of the coordinate regulation of the transcription of genes for ATP production and expenditure. This mechanism will become a therapeutic target for heart failure.

Scaling of mixed structure functions in turbulent boundary layers

We address the issue of the scaling of the anisotropic components of the hierarchy of correlation tensors in the logarithmic region of a turbulent boundary layer over a flat plate, at Reθ≈15000. We isolate the anisotropic observables by means of decomposition tools based on the SO(3) symmetry group of rotations. By employing a dataset made of velocity signals detected by two X probes, we demonstrate that the behavior of the anisotropic fluctuations throughout the boundary layer may be understood in terms of the superposition of two distinct regimes. The transition is controlled by the magnitude of the mean shear and occurs in correspondence with the shear scale. Below the shear scale, an isotropy-recovering behavior occurs, which is characterized by a set of universal exponents which roughly match dimensional predictions based on Lumley’s argument [J. L. Lumley, Phys. Fluids 8, 1056 (1965)]. Above the shear scale, the competition between energy production and transfer mechanisms gives rise to a completely different scenario with strong alterations of the observed scaling laws. This aspect has significant implications for the correct parametrization of the anisotropy behavior in the near wall region since, approaching the wall, an increasingly larger fraction of the scaling interval tends to conform to the shear-dominated power laws.

Anaerobic Elemental Sulfur Reduction by FungusFusarium oxysporum

Reduction of inorganic sulfur compounds by the fungus Fusarium oxysporum was examined. When transferred from a normoxic to an anoxic environment, F. oxysporum reduced elemental sulfur to hydrogen sulfide (H2S). This reaction accompanied fungal growth and oxidation of the carbon source (ethanol) to acetate. Over 2-fold more of H2S than of acetate was produced, which is the theoretical correlation for the oxidation of ethanol to acetate. NADH-dependent sulfur reductase (SR) activity was detected in cell-free extracts of the H2S-producing fungus, and was found to be up-regulated under the anaerobic conditions. On the other hands both O2 consumption by the cells and cytochrome c oxidase activity by the crude mitochondrial fractions decreased. These results indicate that H2S production involving SR was due to a novel dissimilation mechanism of F. oxysporum, and that the fungus adapts to anaerobic conditions by replacing the energy-producing mechanism of O2 respiration with sulfur reduction.

Physical working capacity and energy supply of muscle function during postnatal human ontogeny

On the basis of the results of our studies and literature data, an analysis of the physiological mechanisms responsible for the multifold increase in the physical working capacity during human development has been performed. Physiological and biochemical studies have shown that the aerobic energy system already has a high capacity during the second period of childhood, and the further increase in working capacity is mainly provided by the development of anaerobic mechanisms of energy supply. The maturation of mechanisms of energy production is related to considerable changes in the activity of tissue enzymes and radical rearrangement of the composition of muscular fibers. Puberty considerably influences the development of anaerobic muscle energetics in boys due to stimulation of the growth of type II fibers by testosterone. It has been shown that widespread tests for assessment of physical working capacity mainly reflect changes in the power of energy systems and only in rare cases may be used to characterize changes in their capacity. However, the capacity parameters, which depend to a greater extent on the quality of regulation at the cellular, tissue, and body levels, show multifold growth during ontogeny, which corresponds to the actual increase in the working capacity in the period from childhood to youth. A classification of tests of physical working capacity is proposed. The use and development of this classification may facilitate the development of new tests and an increased efficiency of testing involved in solving various applied and fundamental problems.

Modelling the role of excitatory and inhibitory neuronal activity in the generation of the BOLD signal

A biophysical model of the coupling between neuronal activity and the BOLD signal that allows for explicitly evaluating the role of both excitatory and inhibitory activity is formulated in this paper. The model is based on several physiological assumptions. Firstly, in addition to glycolysis, the “glycogen shunt” is assumed for excitatory synapses as a mechanism for energy production in the astrocytes. As a result, oxygen-to-glucose index (OGI) is not constant but varies with excitatory neuronal activity. In contrast, a constant OGI=6 (glycolysis) is assumed for inhibitory synapses. Finally we assume that cerebral blood flow is not directly controlled by energy usage, but it is only related to excitatory activity. Simulations' results show that increases in excitatory activity amplify the oscillations associated with the transient BOLD response, by increasing the initial dip, the maximum, and the post-stimulus undershoot of the signal. In contrast, increasing the inhibitory activity evoked an overall decrease of the BOLD signal along the whole time interval of the response. Simultaneous increase of both types of activity is then expected to reinforce the initial dip and the post-stimulus undershoot, while respective effects on the maximum tend to counteract each other. Two mechanisms for negative BOLD response (NBS) generation were predicted by the model: (i) when inhibition was present alone or together with low activation levels and (ii) when deactivation occurred independently of the accompanying inhibition level. Interestingly, NBS was associated with negative oxygen consumption changes only for the case of mechanism (ii).

Tumor metabolism: new opportunities for cancer therapy

Mammalian cells depend on extracellular input for the regulation of growth, proliferation and survival. Cancer cells evade these requirements, and are able to take up nutrients in a cell-autonomous fashion, which allows continuous growth and proliferation. To fulfill the high bioenergetic demands imposed by transformation, tumors must develop alternative mechanisms of energy production. Accordingly, the biochemical signature of cancer cells involves a shift to aerobic glycolysis, also known as the "Warburg effect". This property of cancer cells has resulted of great utility in modern medicine for detection of early tumors by positron-emission scanning. Nonetheless, the underlying mechanisms and contribution of the Warburg effect to the malignant phenotype have remained obscure. Thanks to recent advances in cancer research, we are beginning to understand the link between cancer genetics and the abnormal use of glucose by tumors. A new scenario is thus emerging, in which bioenergetics would contribute to and sustain malignant transformation. These findings are not only important for a better understanding of tumorigenesis; tumor reliance on glycolysis can be exploited in the search for novel, more potent therapeutic approaches to cancer treatment.

Invited review: Aging and energy balance.

Humans over 70 yr of age often lose weight. This appears to be due to a physiological anorexia of aging as well as a loss of lean mass (sarcopenia) and, to a lesser extent, fat mass. The causes of the physiological anorexia of aging include changes in taste and smell and a decrease in adaptive relaxation of the fundus of the stomach, which leads to more rapid antral filling and early satiation. In addition, basal and stimulated levels of the satiating hormone, cholecystokinin, are increased. In men, the decline in testosterone leads to an increase in leptin and a loss of lean mass. Although resting metabolic rate declines with aging, this is mainly due to the decline in lean body mass. Energy metabolism is also decreased due to a decline in Na+-K+-ATPase activity, decreased muscle protein turnover, and possibly changes in mitochondrial membrane protein permeability. Physical energy expenditure declines with aging. Meal-induced thermogenesis shows a delay to peak, possibly due to a delay in gastric emptying. Inadequate data are available on the effect of aging in humans on other energy-producing mechanisms such as adaptive thermogenesis. These physiological changes place older men and women at major risk of developing pathological weight loss when they develop disease states, especially those associated with cytokine elaboration.

MHD shocks and the origin of the solar transition region.

Simultaneous observations of the solar atmosphere from its surface to the corona obtained with the Solar and Heliospheric Observatory (SOHO) and Transition Region and Coronal Explorer (TRACE) show a ubiquitous sequence of events that start from cancellation of photospheric magnetic fields, pass through shock formation, and result in transition region supersonic jets and microflares. These results support a novel view of the energy buildup in the solar atmosphere associated with a cascade of shock waves produced by interacting network magnetic elements in the photosphere and provide insight into the origin of the solar transition region. The findings account for the general mechanisms of energy production, transfer, and release throughout the Sun's and stellar atmospheres.

Arginine metabolism by wine Lactobacilli isolated from wine

Lactobacillus hilgardii is a very common heterofermentative bacterium found in wine, associated mainly with several kinds of negative alterations. It is also known as a spoilage organism in soft drinks and other fermented beverages. It is able to break down arginine, one of the most abundant amino acids in wine, through the arginine deiminase (ADI) pathway. The first step of this metabolism may lead to the excretion of citrulline. This feature has an important enological implication since citrulline can react spontaneously with ethanol to form ethyl carbamate. Carcinogenic effects of this compound have been observed when administrated at high concentrations to laboratory animals. To complete the understanding of this catabolic pathway in L. hilgardii, arginine and citrulline utilization were investigated under different conditions. Moreover, ATP production from these amino acids was also monitored. From these data, arginine degradation via the ADI pathway can be considered to be a mechanism of energy production and pH regulation. However, if arginine degradation is beneficial for the bacteria, improving its growing ability and its adaptability, this increases the risk of degradation of the organoleptic and hygienic properties of wine.

Cellular responses to environmental salinity in the halophilic black yeast Hortaea werneckii.

The development of crop plants with increased salt tolerance necessitates the study of naturally salt-tolerant eukaryotic species. We studied the bio-synthesis of glycerol as a compatible solute in the halophilic eukaryotic microorganism, black yeast Hortaea werneckii. A restriction fragment-differential display technique was used to investigate the transcriptome of the organism. Eight differentially expressed genes were identified in response to growth at different salinities. Although the putative functions of their products, P-type ATPase, ubiquinone reductase, aconitase, RNA helicase, Asn-tRNA ligase, isoamyl alcohol oxidase, and phosphatidylinositol-3-kinase, are not intimately related within the cellular machinery, the results presented here are sufficient to propose a model which describes how H. werneckii adapts to extremely high salinities. Some of these mechanisms of adaptation to raised environmental salinity are similar to those in other salt-sensitive species, e.g. glycerol accumulation, there also appear to be novel mechanisms present such as the use of different energy production mechanisms and post-transcriptional regulation of gene expression. Our results have also provided new data on two genes from two other fungal species, the Neurospora crassa B1D1.130 gene and the Aspergillus ustus amdS-A gene.

Anaerobic respiration using Fe(3+), S(0), and H(2) in the chemolithoautotrophic bacterium Acidithiobacillus ferrooxidans.

The chemolithoautotrophic bacterium Acidithiobacillus ferrooxidans has been known as an aerobe that respires on iron and sulfur. Here we show that the bacterium could chemolithoautotrophically grow not only on H(2)/O(2) under aerobic conditions but also on H(2)/Fe(3+), H(2)/S(0), or S(0)/Fe(3+) under anaerobic conditions. Anaerobic respiration using Fe(3+) or S(0) as an electron acceptor and H(2) or S(0) as an electron donor serves as a primary energy source of the bacterium. Anaerobic respiration based on reduction of Fe(3+) induced the bacterium to synthesize significant amounts of a c-type cytochrome that was purified as an acid-stable and soluble 28-kDa monomer. The purified cytochrome in the oxidized form was reduced in the presence of the crude extract, and the reduced cytochrome was reoxidized by Fe(3+). Respiration based on reduction of Fe(3+) coupled to oxidation of a c-type cytochrome may be involved in the primary mechanism of energy production in the bacterium on anaerobic iron respiration.

Hot, cold, and now bubble fusion

For almost 50 years now, physicists have been trying to mimic energy-producing mechanisms that the sun uses. It is very difficult to persuade two people who naturally repel each other to come together-and so it is with nuclear fusion. The hydrogen bomb, a fusion device, needs an atom bomb to get it started. Huge and very expensive experiments with “hot” fusion are still in progress, but a commercially viable machine seems as far away as ever.

Relationship between wall pressure fluctuations and streamwise vortices in a turbulent boundary layer

A direct numerical simulation is performed to examine the relationship between wall pressure fluctuations and near-wall streamwise vortices in a spatially developing turbulent boundary layer. It is found that wall pressure fluctuations are closely linked with the upstream quasistreamwise vortices in the buffer region. The maximum correlation occurs with the spanwise displacement from the location of wall pressure fluctuations. The space–time correlation reveals that wall pressure fluctuations lag behind streamwise vorticity in the upstream, while streamwise vorticity lag behind wall pressure fluctuations in the downstream. The contributions of high-amplitude wall pressure event to the turbulent energy production mechanism are examined by the quadrant analysis of Reynolds shear stress.

A qualitative model for the mechanism of sugar accumulation in cold-stressed plant tissues

Summary Low temperatures induce the accumulation of soluble sugars in plant cells. An attempt is made to identify the primary site of action of low temperatures and the sequence of physiological and biochemical events leading to sugar accumulation. The integration of all the available information points to a central role of increased intracellular calcium ion concentration generated by the inhibition of ATPases concerned with its homeostasis. A positive role of a cold-induced dysfunction of mitochondrial and chloroplast electron flow is also proposed. The biological significance of an explanation of this physiological response to a stress factor relies on its categorization into the major family of those employing alternative energy-producing pathways under stress conditions. More specifically, a connection of sugar mobilization to the needs of the cold-stressed cell to employ fermentative energy-producing mechanisms is made. From this ankle of view, new ways of genetically modifying the ability of plant cells to accumulate sugars become obvious.

FASTING NORMOGLYCEMIA AND KETONE BODY FORMATION IN A CHILD WITH GLUCOSE-6-PHOSPHATASE DEFICIENCY

108 Gycogenosis type-1a (GSD1a), due to glucose-6-phosphatase (G6P) deficiency, is usually associated with fasting hypoglycemia via defective glucose production (gluconeogenesis and glycogenolysis). Although patients with GSD-1a may generate some glucose from glycogen by a yet unclear mechanism, it is insufficient to prevent hypoglycemia. Whether ketone body (KB) formation occurs in GSD-1a remains controversial. We describe a 22 month old male infant with clinical, biochemical, histologic, histochemical and hepatic tissue enzyme and immunoblot analysis typical of GSD-1a, who tolerated prolonged fasting associated with KB formation while normalizing serum glucose and lactate levels. (Table) The unusual metabolic response to fasting in this child with GSD-1a was not due to residual G6P activity, as no immuno-reactivity for the G6P protein was detected. This case illustrates the phenotypic heterogeneity of this disorder and the need for further study into the mechanisms of energy production in hepatic glycogenoses.TABLE

Biology and ultra-structure of Trypanosoma cruzi: a 90-year old challenge for scientists.

When Dr Carlos Chagas first observed underthe microscope the flagellate that he named Schizot-rypanum cruzi (today known as Trypanosomacruzi), in honor of his master and friend OswaldoCruz, he began to study the biology of this inter-esting microorganism (Chagas 1909). This uniquefact in medicine, a single person’s discovery andreport of the clinical picture of a new disease, witha new etiological agent, its life cycle, its vectorsand wild reservoirs, were later explained by him-self (Chagas 1922): a process that he was able tounderstand after the intense and basic studies onthe biology of this parasite, carried out at theOswaldo Cruz Institute. In Chagas’ own words“...quando no sangue periferico de uma criancafebril, observamos o flagelado patogenico, de suabiologia ja possuiamos nocao completa, adquiridaem demorados estudos anteriores” “...when wefound the pathogenic flagellate in the blood of achildren, we had already a complete notion of itsbiology, acquired under previous and detailed stud-ies” (Chagas 1922).Since then, the intriguing biology of this spe-cial parasite has been studied. Its morphology, de-picted under the optical microscopy of CarlosChagas and Garpar Vianna, was first investigatedunder an electron microscope by Dr Hertha Meyer(Meyer & Porter 1954). Dr Carlos Chagas Filho,Chagas’ son who founded in Rio de Janeiro thefamous Institute of Biophysics that later took hisname, achieved to establish Dr Hertha Meyer inthis Institute during the II World War. She starteda whole school of cell biology of T. cruzi (as wellas other tropical disease parasites), introducing invitro cell culture of muscle and nerve cells, andthe ultrastructure study of all the parasite develop-mental stages (reviewed in De Souza 1984). SinceDr Chagas’ time, some basic questions still chal-lenge the intelligence and curiosity of scientists allover the world. Why and how does the parasiteevolve among three different morphological andfunctional states of differentiation over its life cycle(ama-, epi- and trypomastigotes)? Does the T. cruzislender and stout forms found in blood stream ofdifferent host represent sexual dimorphism or any-thing else? How does T. cruzi enter so many dif-ferent cells? How does at least part of the parasitepopulation that infects a person or animal escapethe vigorous specific immune response elicited inthe host by the infection, leading to the finding ofviable forms during the decades-lasting chronic de-velopment of the disease?During the 90 years that followed since Chagas’classic report of a new disease, much informationwas obtained on the biology and ultrastructure ofits causative agent. Recent reviews from DrWanderley De Souza (1984, 1995) summarize theknowledge in this area. A large knowledge wasobtained on the understanding of its clonal com-position (Heckert et al. 1994, Tibayrenc 1995), aswell as in its population distribution and associ-ated biological and molecular markers (Zingaleset al. 1998). Another important field on parasitebiology investigation concerns its metabolic path-ways (reviewed in Cazzulo 1992), that engages thedesign of new drugs based on differences encoun-tered. Key organelles from which the parasite getsenergy such as acid calcisomes (DoCampo et al.1995) and reservosomes (Figueiredo et al. 1994)are under intense study. The same happens withsome pivotal enzymes for the parasite that are in-volved in energy production (such as glycosomalenzymes, purine and sterol byosynthetic pathways),detoxification (such as trypanothione reductase, or-nithine decarboxylase and S-adenosylmethioninedecarboxylase), or virulence (such as cysteine pro-teases) mechanisms. Second generation anti-try-panocidal drugs will certainly emerge from thisfield of research (Krauth-Siegel & Schoneck 1995,Cazzulo et al. 1997, Croft 1999, Urbina 1999) tosubstitute for the same two old and toxic drugs thatare currently available for clinical use since thesixties (benznidazole and nifurtimox).

A stratospheric chemical reaction controlling climatic change

The present mechanism of radiant energy production in the atmosphere is considered and it is shown that it is not compatible with accepted principles of physics. An alternative mechanism whereby the temperature of the atmosphere and surface of the Earth is regulated by a chemical reaction in the stratosphere is described. It is shown that this mechanism can account for the changes in climate which occurred during the past ten thousand years. The effect on this mechanism of changes in the composition of atmospheric gases, including changes resulting from human activities, is described and the consequences of the changes recorded.

Mitochondrial Energy Metabolism in the Left Ventricular Tissue of Spontaneously Hypertensive Rats: Abnormalities in both Adeninenucleotide and Phosphate Translocators and Enzyme Adenylate-Kinase and Creatine-Phosphokinase Activities

The aim of this study was to investigate the oxidative phosphorylation and additional adenosinetriphosphate (ATP) production mechanisms in mitochondria isolated from hypertrophied left ventricles of spontaneously hypertensive rats (SHR). Measurements of adenosinediphosphate (ADP)/ ATP and inorganic phosphate (Pi) carrier activities showed a significant reduction of Vmax values thus suggesting a general decrease of ATP supply in the hypertrophied ventricles. Investigation of mitochondrial enzyme activities showed 45% and 90% increases of adenylate-kinase and 80% and 110% increases of creatine-phosphokinase in 5- and 24-week-old SHR, before and after the development of the hypertensive state, respectively. The abnormalities found in SHR at the mitochondrial level suggest a profound rearrangement of energy production mechanisms in this model of left ventricular hypertrophy; whether the defects are determined genetically, and then worsen with the hypertensive state, remains to be determined.