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At least 433 records · Page 24

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NASA NTRS1985

Role of Glucocorticoids in the Response to Unloading of Muscle Protein and Amino Acid Metabolism

Intact control (weight bearing) and suspended rats gained weight at a similar rate during a 6 day period. Adrenaectomized (adx) weight bearing rats gained less weight during this period while adrenalectomized suspended rats showed no significant weight gain. Cortisol treatment of both of these groups of animals caused a loss of body weight. Results from these studies show several important findings: (1) Metabolic changes in the extensor digitorum longus muscle of suspended rats are due primarily to increased circulating gluccorticoids; (2) Metabolic changes in the soleus due to higher steroid levels are probably potentiated by greater numbers of receptors; and (3) Not all metabolic responses in the unloaded soleus muscle are due to direct action of elevated glucocorticoids or increased sensitivity to these hormones.

Tischler, M. E.↗

NASA NTRS1985

Spaceflight and calcium metabolism

Calcium metabolism data from spaceflight have been obtained primarily from Skylab astronauts, from Soviet Salyut-6 cosmonauts, and from growing rats flown either on the Soviet Cosmos series or Spacelab 3. In this report, the results from Skylab astronauts will be compared to data from bed rested subjects, and the results from Cosmos rats will be compared to data from a ground-based rat model, to help explain (1) how spaceflight or gravitational unloading alters calcium metabolism in adult humans and growing rats, (2) the relevance of the observations of bone dynamics in growing rats to the changes in adult man, and (3) the sequence of events leading to changes in calcium metabolism during spaceflight. A hypothetical scheme of the mechanisms causing altered bone mass during spaceflight will be proposed.

Morey-Holton, E. R.↗

NASA NTRS1985

Changes in functional metabolism in the rat central nervous system following spaceflight

The neuronal metabolism and soma size of neurons within the paraventricular nucleus (PVN) and the supraoptic nucleus of rats are analyzed. Five male Sprague-Dawley rats were flown on Spacelab 3 for 7 days under a 12:12 light/dark cycle and unlimited food and water, and a control group was kept on the ground under similar conditions. The preparation of the hypothalamus of the rats for microscopic examination using thionin or the cytochrome oxidase (CYOX) technique is described. CYOX activity and soma size within the PVN are evaluated. The effects of water drinking pattern and space flight on CYOX activity and soma size are investigated. The data reveal that the flight rats with normal drinking patterns display a decrease in neuronal metabolism within the vasopressin-containing neurons of the hypothalamus and this metabolic change may reflect fluid shifts caused by microgravity.

Murakami, D. M.↗

NASA NTRS1988

Use of diphosphonates to correct disorders in calcium metabolism and mineral composition of bone tissue with 60-day hypokinesia in rats

Compounds of the diphosphonate group suppress bone resorption and bone tissue metabolism, from which it was assumed that they can be used for the prevention of osteoporosis and disorders of calcium homeostasis in humans during space flight. Two compounds of this group were used for preventive purposes in 60 day hypokinesia in rats. The results showed that diphosphonates have a marked effect on calcium metabolism and the condition of the bone tissues under conditions of long term hypokinesia: they reduce the content of ionized calcium in blood, delay the loss of calcium and phosphorus by the bone tissue, and to a considerable degree prevent reduction of bone density. This confirms the possibility of using compounds of this group for correcting and preventing changes of bone tissue and mineral metabolism during long term hypokinesia.

Morukov, B. V.↗

NASA NTRS1987

The effect of fluid mechanical stress on cellular arachidonic acid metabolism

The effect of sublytic levels of mechanical perturations of cells on cell metabolism were investigated by analyzing the products of arachidonic acid (used as a marker metabolite) in blood platelets, polymorphonuclear leucocytes, and cultured umbilical-vein endothelial cells after the suspensions of these cells were subjected to a shear stress in a modified viscometer. It is shown that the sublytic levels of mechanical stress stimulated the arachidonic acid metabolism in all these cell types. Possible biological implications of this stress-metabolism coupling are discussed.

Mcintire, L. V.↗

NASA NTRS1992

Metabolic response of environmentally isolated microorganisms to industrial effluents: Use of a newly described cell culture assay

An environmental application using a microtiter culture assay to measure the metabolic sensitivity of microorganisms to petrochemical effluents will be tested. The Biomedical Operations and Research Branch at NASA JSC has recently developed a rapid and nondestructive method to measure cell growth and metabolism. Using a colorimetric procedure the uniquely modified assay allows the metabolic kinetics of prokaryotic and eukaryotic cells to be measured. Use of such an assay if adapted for the routine monitoring of waste products, process effluents, and environmentally hazardous substances may prove to be invaluable to the industrial community. The microtiter method as described will be tested using microorganisms isolated from the Galveston Bay aquatic habitat. The microbial isolates will be identified prior to testing using the automated systems available at JSC. Sodium dodecyl sulfate (SDS), cadmium, and lead will provide control toxic chemicals. The toxicity of industrial effluent from two industrial sites will be tested. An effort will be made to test the efficacy of this assay for measuring toxicity in a mixed culture community.

Ferebee, Robert N.↗

NASA NTRS1993

Endocrine and metabolic changes in payload specialist (L-1)

The endocrine system plays an important role in the adaptation to unusual environments by secreting hormones to control metabolism. Since human beings have long evolved on the surface of the Earth under a gravity environment, the weightless environment must be quite unusual for them. The purpose of this experiment is to study the mechanisms of human adaptation to a weightless environment from endocrine and metabolic changes. Our study plan is focused on four major physiological changes which were reported during past space flights or which may be expected to occur under that condition: (1) hormone and metabolic changes associated with fluid shift; (2) bone demineralization and muscle atrophy; (3) altered circadian rhythm; and (4) stress reaction during space flight.

Matsui, Nobuo↗

NASA NTRS1995

On the levels of enzymatic substrate specificity: Implications for the early evolution of metabolic pathways

The most frequently invoked explanation for the origin of metabolic pathways is the retrograde evolution hypothesis. In contrast, according to the so-called 'patchwork' theory, metabolism evolved by the recruitment of relatively inefficient small enzymes of broad specificity that could react with a wide range of chemically related substrates. In this paper it is argued that both sequence comparisons and experimental results on enzyme substrate specificity support the patchwork assembly theory. The available evidence supports previous suggestions that gene duplication events followed by a gradual neoDarwinian accumulation of mutations and other minute genetic changes lead to the narrowing and modification of enzyme function in at least some primordial metabolic pathways.

Lazcano, A.↗

NASA NTRS1996

Effect of Diet on Metabolism of Laboratory Rats

In previous studies when rats were fed a processed, semipurified, extruded rodent food bar (RFB) developed for space science research, we noted a difference in the appearance of gastrointestinal tissue (GI); therefore the following study evaluated GI characteristics and growth and metabolic rates of rats fed chow (C) or RFB. Two hundred and twenty-four rats (78 g mean body weight) were randomly assigned to 28 cages and provided C or RFB. Each cage was considered the experimental unit and a 95 percent level of significance, indicated by ANOVA, was used for inference. After each 30-, 60-, and 90-day period, eight cages were shifted from the C to RFB diet and housing density was reduced by two rats per cage. The two rats removed from each cage were sacrificed and used for GI evaluation. Metabolic rates of the rats in each cage were determined by indirect calorimetry. No differences in body weight were detected at 0, 30, 60 or 90 days between C and RFB. Heat production (kcal/hr/kg), CO2 production (L/hr/kg) and O2 consumption (L/hr/kg) were different by light:dark and age with no effect of diet. Respiratory quotient was different by age with no effect of light:dark or diet. Rats on the C diet ate less food and drank more water than those on RFB. C rats produced more fecal and waste materials than the RFB. GI lengths increased with age but were less in RFB than C. GI full and empty weights increased with age but weighed less in RFB than C. Gut-associated lymphoid tissue (GALT) numbers increased with age with no effect of diet. No differences in ileum-associated GALT area were detected between C and RFB. Switching C to RFB decreased GI length, GI full and empty weights, with no changes in GALT number or area. We concluded RFB decreased GI mass without affecting metabolic rate or general body growth.

Harrison, P. C.↗

NASA NTRS1994

Experiment K-7-35: Circadian Rhythms and Temperature Regulation During Spaceflight: Metabolism - Part 2

Energy expenditure can be regarded as the sum of two components; the basal metabolic rate and the energy costs of activity. Weight loss is usually associated with an energy deficit. A negative energy balance exists when energy intake is less that energy utilization. The deficit is made up by tissue catabolism (principally fat, but also some protein). By analyzing food and water intake, urine and fecal output, and changes in body weight, the Skylab investigators reached the unexpected conclusion that energy expenditure during spaceflight was about 5% greater than at 1 G (Leonard, 1983; Rambaut et al., 1977). Possible explanations for the human metabolic responses are an increased workload during spaceflight (Leonard, 1983), or as Rambaut and co-workers (1977) suggested, a progressive decrease in metabolic efficiency. It is likely to be very difficult to distinguish between these two possibilities in man because the activity component may be different during spaceflight than it is the ground. The problem is to measure energy expenditure with efficient precision during spaceflight in a non-invasive manner which will not interfere with other investigations or take an time. The doubly labeled water (DLW) method meets these criteria. The DLW method is the only method available for continuously measuring energy expenditure during spaceflight given the severely restricted conditions in the spaceflight environment. Therefore, this study focuses on the development and use of this procedure on nonhuman primates during spaceflight. Energy expenditure and total body water was determined in two Rhesus monkeys by the doubly labeled water (2H2'80) method. Three determinations were made. Monkey B (#2483) was studied twice, during the flight of COSMOS 2044 and during a follow-up ground control study a month later. A second monkey was studied on the ground only (Monkey D, #782).

Fuller, C. A.↗

NASA NTRS1996

The Metabolic World: Sugars as an Energized Carbon Substrate for Prebiotic and Biotic Synthesis

To understand the origin of metabolism and biopolymer synthesis we investigated the energy sources that drive anabolic metabolism. We found that biosynthesis of amino acids and lipids from sugars is driven bz the free energy of redox disproportionation of carbon (see discussion or next page). The indispensable role of sugar disproportionation in the biosynthesis of amino acids and lipids suggests that the origin of life uses the same chemical engine, and was therefore based on nonenzymatic redox disproportionation reactions of sugars that occurred in the presence o ammonia and hydrogen sulfide. The chemistry of this 'metabolic' model of the origin of life is described.

Weber, Arthur L.↗

NASA NTRS2000

Dietary Sodium Effects on Bone Loss and Calcium Metabolism During Bed Rest

The acceleration of age-related bone loss is one of the most detrimental effects of space flight. The ability to understand and counteract this loss will be critical for crew health and safety during and after long-duration missions. Studies in healthy ambulatory individuals have linked high salt (sodium) diets, hypercalciuria, and increased renal stone risk. Dietary salt may modulate bone loss through changes in calcium metabolism and the calcium endocrine system. The research proposed here will determine the role of dietary salt in the loss of bone during simulated space flight. Calcium metabolism will be determined through calcium kinetics studies, endocrine and biochemical measurements; and estimates of the mass, distribution and mechanical properties of bone, in subjects fed low (100 mmol sodium/day) or high (250 mmol sodium/day) levels of dietary salt during 28 days of headdown tilt bedrest. This research addresses the role of dietary salt in the loss of bone and calcium in space flight, and integrates the changes in calcium metabolism with those occurring in other physiologic systems. These data will be critical for both countermeasure development, and in determination of nutritional requirements for extended-duration space flight. The potential countermeasures resulting from this research will reduce health risks due to acceleration of age-related osteoporosis and increased risk of renal stone formation..

Smith, Scott M.↗

NASA NTRS2001

Chemical Constraints Governing the Origin of Metabolism: The Thermodynamic Landscape of Carbon Group Transformations

The thermodynamics of organic chemistry under mild aqueous conditions was examined in order to begin to understand its influence on the structure and operation of metabolism and its antecedents. Free energies were estimated for four types reactions of biochemical importance carbon-carbon bond cleavage and synthesis, hydrogen transfer between carbon groups, dehydration of alcohol groups, and aldo-keto isomerization. The energies were calculated for mainly aliphatic groups composed of carbon, hydrogen, and oxygen. The energy values showed that (1) when carbon-carbon bond cleavage involves two different types of functional groups, transfer of the shared electron-pair to the more reduced carbon group is energetically favored over transfer to the more oxidized carbon group, and (2) the energy of carbon-carbon bond transformation is strongly dependent on the type of functional group that donates the shared electron-pair during cleavage, and the group that accepts the shared electron-pair during synthesis, and (3) the energetics of C-C bond transformation is determined primarily by the half-reaction energies of the couples: carbonyl/carboxylic acid, carboxylic acid/carbon dioxide, alcohol/carbonyl, and hydrocarbon/alcohol. The energy of hydrogen-transfer between carbon groups was found to depend on the functional group class of both the hydrogen-donor and hydrogen-acceptor. From these and other observations we concluded that the chemistry of the origin of metabolism (and to a lesser degree modem metabolism) is strongly constrained by the (1) limited disproportionation energy of organic substrates that can be dissipated in a few irreversible reactions, (2) the energy-dominance of few half-reaction couples in carbon-carbon bond transformation that establishes whether a chemical reaction is energetically irreversible, reversible or unfeasible, and (3) the dependence of the transformation-energy on the oxidation state of carbon groups (functional group type) which is contingent on prior reactions in the synthetic pathway.

Weber, Arthur L.↗

NASA NTRS2003

Second Law of Thermodynamics Applied to Metabolic Networks

We present a simple algorithm based on linear programming, that combines Kirchoff's flux and potential laws and applies them to metabolic networks to predict thermodynamically feasible reaction fluxes. These law's represent mass conservation and energy feasibility that are widely used in electrical circuit analysis. Formulating the Kirchoff's potential law around a reaction loop in terms of the null space of the stoichiometric matrix leads to a simple representation of the law of entropy that can be readily incorporated into the traditional flux balance analysis without resorting to non-linear optimization. Our technique is new as it can easily check the fluxes got by applying flux balance analysis for thermodynamic feasibility and modify them if they are infeasible so that they satisfy the law of entropy. We illustrate our method by applying it to the network dealing with the central metabolism of Escherichia coli. Due to its simplicity this algorithm will be useful in studying large scale complex metabolic networks in the cell of different organisms.

Nigam, R.↗

NASA NTRS2000

Systematic Sensitivity Analysis of Metabolic Controllers During Reductions in Skeletal Muscle Blood Flow

An acute reduction in oxygen delivery to skeletal muscle is generally associated with profound derangements in substrate metabolism. Given the complexity of the human bioenergetic system and its components, it is difficult to quantify the interaction of cellular metabolic processes to maintain ATP homeostasis during stress (e.g., hypoxia, ischemia, and exercise). Of special interest is the determination of mechanisms relating tissue oxygenation to observed metabolic responses at the tissue, organ, and whole body levels and the quantification of how changes in oxygen availability affect the pathways of ATP synthesis and their regulation. In this study, we apply a previously developed mathematical model of human bioenergetics to study effects of ischemia during periods of increased ATP turnover (e.g., exercise). By using systematic sensitivity analysis the oxidative phosphorylation rate was found to be the most important rate parameter affecting lactate production during ischemia under resting conditions. Here we examine whether mild exercise under ischemic conditions alters the relative importance of pathways and parameters previously obtained.

Radhakrishnan, Krishnan↗

NASA NTRS2002

Calcium metabolism and cardiovascular function after spaceflight

To determine the influence of dietary calcium on spaceflight-induced alterations in calcium metabolism and blood pressure (BP), 9-wk-old spontaneously hypertensive rats, fed either high- (2%) or low-calcium (0.02%) diets, were flown on an 18-day shuttle flight. On landing, flight animals had increased ionized calcium (P < 0.001), elevated parathyroid hormone levels (P < 0.001), reduced calcitonin levels (P < 0.05), unchanged 1,25(OH)(2)D(3) levels, and elevated skull (P < 0.01) and reduced femur bone mineral density. Basal and thrombin-stimulated platelet free calcium (intracellular calcium concentration) were also reduced (P < 0.05). There was a tendency for indirect systolic BP to be reduced in conscious flight animals (P = 0.057). However, mean arterial pressure was elevated (P < 0.001) after anesthesia. Dietary calcium altered all aspects of calcium metabolism (P < 0.001), as well as BP (P < 0.001), but the only interaction with flight was a relatively greater increase in ionized calcium in flight animals fed low- compared with high-calcium diets (P < 0.05). The results indicate that 1) flight-induced disruptions of calcium metabolism are relatively impervious to dietary calcium in the short term, 2) increased ionized calcium did not normalize low-calcium-induced elevations of BP, and 3) parathyroid hormone was paradoxically increased in the high-calcium-fed flight animals after landing.

NASA Discipline Cardiopulmonary↗

NASA NTRS1988

Carbon metabolism of the cryptoendolithic microbiota from the Antarctic desert

The carbon metabolism of the cryptoendolithic microbiota of sandstones from the Ross Desert of Antarctica was studied in situ and in vitro. Organic and inorganic carbon compounds were metabolized by the microbiota, with bicarbonate incorporation into community lipids occurring primarily in the light. Light intensity affected the photometabolism of carbon with a photosynthesis-intensity response optimum at about 200 to 300 micromoles of photons per m2 per s. Photosynthesis was also affected by temperature, with a minimum activity at -5 degrees C, an optimum activity at 15 degrees C, and complete inhibition at 35 degrees C, indicating that the cryptoendolithic community was psychrophilic. The primary source of CO2 for photosynthesis in situ was the atmosphere. CO2 may also be photometabolized by using the carbon produced from respiration within the endolithic community. Photosynthesis occurred maximally when the microbiota was wet with liquid water and to a lesser extent in a humid atmosphere. This simple microbial community, therefore, exists under extremes of water, light, and temperature stress which affect and control its metabolism.

NASA Discipline Exobiology↗

NASA NTRS1998

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

Non-NASA Center↗