SEARCH · Search NASA

Results for “metabolic pathways”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7

All sources NASA NTRS DOE OSTI

NASA NTRS1993

Cellular responses to low-gravity: Pilot studies on suborbital rockets and orbiting spacecraft

The allocated funding supported, in part, experiments conducted on two Consort sounding rockets and five Shuttle flights. The primary parameters investigated were signal transduction in response to various mediators, cellular differentiation and metabolism in microgravity, and effect of microgravity on cytoskeletal morphology. Achievements include: demonstration of effect of spaceflight on the actin cytoskeleton in mouse osteoblasts and frog cells; confirmation that the T cell receptor-mediated signal transduction pathway in T lymphocytes is not affected by low-gravity compared to non-TCR-mediated stimulation (Con-A) which classically does not promote proliferative response; indication that microgravity may allow separation of proliferative signaling and secretory function in lymphocytes; demonstration that T lymphocytes and bone cells utilized less glucose indicating a shift in metabolism and confirming Spacelab results with WI-38 cells which used significantly less glucose, during spaceflight; confirmation that activation of human splenic B cells with a number of different mediators is not affected during spaceflight; demonstration of increased prostaglandin synthesis during reduced bone cell growth suggesting an effect of microgravity on prostaglandin-induced mitogenesis. The funding contributed significantly to the database described above and resulted in submission of six collaborative abstracts in 1993 (five to the ASGSB Annual Meeting and one to the ASCB Annual Meeting). Two abstracts were presented at the 1992 ASGSB Annual Meeting in Tucson. In addition, several peer reviewed papers are being generated and data will be included as background in preparation of future proposals, which hopefully will allow us to continue this type of extremely productive collaborative research.

Lewis, Marian L.↗

NASA NTRS1971

The influence of starvation upon hepatic drug metabolism in rats, mice, and guinea pigs.

Male rats, mice, and guinea pigs were starved for 1, 2, or 3 days, and the metabolism of ethylmorphine, p-nitroanisole, and aniline was studied. Results suggest that the oxidative enzyme systems studied are not interdependent, and the pathways studied appear to be species dependent.

Furner, R. L.↗

NASA NTRS1987

Origin and evolution of osmoregulatory mechanisms in blue-green algae (cyanobacteria) as a function of metabolic and structural complexity: Reflections of Precambrian paleobiology

Major accomplishments underlying the basic understanding of cyanobacterial resistance to salt tolerance and osmotic stress were made. The methodology proposed included: the tracing of the pathways of formation of osmoregulatory solutes by traditional methods involving C-14 labelled substrates; gas chromatography; amino acid analysis; X-ray analysis using scanning transmission electron microscopy; and most importantly, C-13 labelled substrates, followed by Nuclear Magnetic Resonance (NMR) spectroscopy. It was found that the cyanobacteria employ a diversity of organic, osmoregulatory solutes. Osmoregulatory solutes were found to serve four functions: adjustment of water activity, noninhibition of enzymes; lowering of K sub m of enzymes to allow functioning at normal levels when the intracellular salt accumulates, and extending the pH optimum of enzymes as intracellular pH rises due to proton-potassium ion pump action during osmoregulation. Differences in osmoregulatory solutes may, but are not always, be attributed to differences in nutritional capabilities. The mechanism of osmoregulation and concomitant salt tolerance in halophilic cyanobacteria was elucidated. The activities of betaine and S-Adenosylhomocysteine hydrolase are discussed.

Yopp, John H.↗

NASA NTRS2015

Metabolic Precursors in Astrophysical Ice Analogs: Implications for Meteorites and Comets

We report the synthesis of complex organic compounds including nicotinic and quinolinic acid, two members involved in the nicotinamide adenine dinucleotide (NAD) biosynthetic pathway, in irradiated astrophysical ice analogs. If delivered to Earth by meteorites and comets, these compounds may have contributed to the origin and early evolution of life.

quinolinic acid↗

NASA NTRSDate not supplied

Transcriptomic Analysis of ISS Crewmembers’ Peripheral Blood Mononuclear Cells Reveals Homeostatic Regulations in Space

The impact of spaceflight on the immune system has been investigated for decades. Studies conducted in cell models, animals and humans suggest that the spaceflight environment affects the innate and acquired immune systems, as the ability to recognize antigens, defend against foreign invaders, and orchestrate repair is significantly hindered. However, the molecular mechanisms behind spaceflight-induced immune dysregulations are still unclear. In this study, blood from eleven (11) International Space Station (ISS) crewmembers was collected before, during and after long duration space missions, as well as from 11 matched ground control subjects. Transcriptomic analysis was performed in isolated peripheral blood mononuclear cells (PBMCs) using the RNA-sequencing technique. In comparison to the blood samples collected from the crewmembers pre-flight, a total of ~1000 genes were found to be upregulated and ~1000 genes downregulated in PBMC collected between 4 and 6 months after they were in space. The most significantly DEGs (differentially expressed genes) include activation of RUBCNL which is an autophagy enhancer and inhibition of GRASP which regulates cell trafficking. Genes involved in cell adhesion, cell cycle progression and other functions were also dysregulated. Pathway analysis of the DEGs indicates mitochondria dysfunction, particularly reduced ATP production in the electron transport chain. Other pathways impacted by spaceflight include glycolysis, autophagy and inflammatory response. Our results suggest that, in space, blood cells may have also experienced energy depletion and reduced metabolism. Consequently, the cells may become autophagic, which is a known homeostatic mechanism for blood cells to become quiescent, but to stay alive. Further analysis of the data shows recovery of the crewmembers after mission and potential differential responses between genders to the space environment. Our data potentially explains some of the physiological changes that have been observed in space such as mitochondria dysfunction, inhibition of T cell activation and telomere lengthening. Comparison of our results with other transcriptomics studies of ISS crewmembers’ blood cells will also be presented.

Maria Moreno Villanueva↗

NASA NTRS1982

Evolution of major metabolic innovations in the Precambrian

A combination of information on the metabolic capabilities of prokaryotes with a composite phylogenetic tree depicting an overview of prokaryote evolution based on the sequences of bacterial ferredoxin, 2Fe-2S ferredoxin, 5S ribosomal RNA, and c-type cytochromes shows three zones of major metabolic innovation in the Precambrian. The middle of these, which reflects the genesis of oxygen-releasing photosynthesis and aerobic respiration, links metabolic innovations of the anaerobic stem on the one hand and, on the other, proliferation of aerobic bacteria and the symbiotic associations leading to the eukaryotes. Those pathways where information on the structure of the enzymes is known are especially considered. Halobacterium and Thermoplasma (archaebacteria) do not belong to a totally independent line on the basis of the composite tree but branch from the eukaryote cytoplasmic line.

Barnabas, J.↗

NASA NTRS2002

Activation of c-Jun N-terminal kinase and apoptosis in endothelial cells mediated by endogenous generation of hydrogen peroxide

Reactive oxygen species have been implicated in the activation of signal transduction pathways. However, extracellular addition of oxidants such as hydrogen peroxide (H2O2) often requires concentrations that cannot be readily achieved under physiological conditions to activate biological responses such as apoptosis. Explanations for this discrepancy have included increased metabolism of H2O2 in the extracellular environment and compartmentalization within the cell. We have addressed this issue experimentally by examining the induction of apoptosis of endothelial cells induced by exogenous addition of H2O2 and by a redox cycling agent, 2,3-dimethoxy-1,4-naphthoquinone, that generates H2O2 in cells. Here we show that low nanomolar steady-state concentrations (0.1-0.5 nmol x min(-1) x 10(6) cells) of H2O2 generated intracellularly activate c-Jun N terminal kinase and initiate apoptosis in endothelial cells. A comparison with bolus hydrogen peroxide suggests that the low rate of intracellular formation of this reactive oxygen species results in a similar profile of activation for both c-Jun N terminal kinase and the initiation of apoptosis. However, a detailed analysis reveals important differences in both the duration and profile for activation of these signaling pathways.

Non-NASA Center↗

NASA NTRS1990

Oxidation kinetics of model compounds of metabolic waste in supercritical water

In this NASA-funded study, the oxidation kinetics of methanol and ammonia in supercritical water have been experimentally determined in an isothermal plug flow reactor. Theoretical studies have also been carried out to characterize key reaction pathways. Methanol oxidation rates were found to be proportional to the first power of methanol concentration and independent of oxygen concentration and were highly activated with an activation energy of approximately 98 kcal/mole over the temperature range 480 to 540 C at 246 bar. The oxidation of ammonia was found to be catalytic with an activation energy of 38 kcal/mole over temperatures ranging from 640 to 700 C. An elementary reaction model for methanol oxidation was applied after correction for the effect of high pressure on the rate constants. The conversion of methanol predicted by the model was in good agreement with experimental data.

Webley, Paul A.↗

NASA NTRS1994

Practical and clinical nutritional concerns during spaceflight

Experience with space exploration to date has raised more questions regarding nutritional requirements for astronauts than it has answered. As mission lengths continue to increase, nutrient imbalances due to alterations in intake, dietary requirements, bioavailability, or excretion, may become more important. Factors adversely affecting intake include those as straightforward as stress and as complex as space-adaptation syndrome. Metabolic alterations induced by shifts in fluid and electrolyte balance, neuroendocrine function, and changes in hepatic protein synthesis and skeletal muscle type that result in nutrient partitioning to different biochemical pathways may also affect dietary requirements. Food processing effects on nutrient stability and digestibility, which apply to limited quantities of our usual diet on Earth, may become more important for diets that contain little fresh food during extended-length missions. Whereas nutrient and water recycling through ecosystems is taken for granted on Earth, specific effects of trace contaminant accumulation will require greater attention for prolonged space flights. Human factors, esthetics, and user-friendly operations will be necessary to facilitate the psychological as well as physiological health of the astronauts.

Review, Tutorial↗

NASA NTRS2000

Regulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes

Sucrose (Suc) plays a central role in plant growth and development. It is a major end product of photosynthesis and functions as a primary transport sugar and in some cases as a direct or indirect regulator of gene expression. Research during the last 2 decades has identified the pathways involved and which enzymes contribute to the control of flux. Availability of metabolites for Suc synthesis and 'demand' for products of sucrose degradation are important factors, but this review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase (SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases. Recent progress has included the cloning of genes encoding these enzymes and the elucidation of posttranslational regulatory mechanisms. Protein phosphorylation is emerging as an important mechanism controlling SPS activity in response to various environmental and endogenous signals. In terms of Suc degradation, invertase-catalyzed hydrolysis generally has been associated with cell expansion, whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes (e.g., cell wall or storage products). Recent results indicate that SuSy may be localized in multiple cellular compartments: (1) as a soluble enzyme in the cytosol (as traditionally assumed); (2) associated with the plasma membrane; and (3) associated with the actin cytoskeleton. Phosphorylation of SuSy has been shown to occur and may be one of the factors controlling localization of the enzyme. The purpose of this review is to summarize some of the recent developments relating to regulation of activity and localization of key enzymes involved in sucrose metabolism in plants.

NASA Discipline Plant Biology↗

NASA NTRS1985

Carbon and nitrogen biogeochemistry in the ocean: A study using stable isotope natural abundance

Determining the biogeochemical pathways traveled by carbon and nitrogen in the ocean is fundamental to the understanding of how the ocean participates in the cycling of these elements within the biosphere. Because biological production, metabolism, and respiration can significantly alter the natural abundance of C-13 and N-15, these abundances can provide important information about the nature of these biological processes and their variability in the marine environment. The research initially seeks to characterize the spatial and temporal patterns of stable isotope abundances in organic matter, and to relate these abundances to C and N biogeochemical processes within selected areas of the northeastern Pacific Ocean.

Rau, G. H.↗

NASA NTRS1997

Lignin Formation and the Effects of Gravity: A New Approach

Two aspects of considerable importance in the enigmatic processes associated with lignification have made excellent progress. The first is that, even in a microgravity environment, compression wood formation, and hence altered lignin deposition, can be induced upon mechanically bending the stems of woody gymnosperms. It now needs to be established if an organism reorientating its woody stem tissue will generate this tissue in microgravity, in the absence of externally applied pressure. If it does not, then gravity has no effect on its formation, and instead it results from alterations in the stress gradient experienced by the organism impacted. The second area of progress involves establishing how the biochemical pathway to lignin is regulated, particularly with respect to selective monolignol biosynthesis. This is an important question since individual monomer deposition occurs in a temporally and spatially specific manner. In this regard, the elusive metabolic switch between E-p-coumaryl alcohol and E-coniferyl alcohol synthesis has been detected, the significance of which now needs to be defined at the enzyme and gene level. Switching between monolignol synthesis is important, since it is viewed to be a consequence of different perceptions by plants in the gravitational load experienced, and thus in the control of the type of lignification response. Additional experiments also revealed the rate-limiting processes involved in monolignol synthesis, and suggest that a biological system (involving metabolite concentrations, as well as enzymatic and gene (in)activation processes) is involved, rather than a single rate-limiting step.

Lewis, Norman G.↗

NASA NTRS2002

Oxidative stress inhibits caveolin-1 palmitoylation and trafficking in endothelial cells

During normal and pathological conditions, endothelial cells (ECs) are subjected to locally generated reactive oxygen species, produced by themselves or by other vessel wall cells. In excess these molecules cause oxidative injury to the cell but at moderate levels they might modulate intracellular signalling pathways. We have investigated the effect of oxidative stress on the palmitoylation and trafficking of caveolin-1 in bovine aortic ECs. Exogenous H2O2 did not alter the intracellular localization of caveolin-1 in ECs. However, metabolic labelling experiments showed that H2O2 inhibited the trafficking of newly synthesized caveolin-1 to membrane raft domains. Several mechanisms potentially responsible for this inhibition were examined. Impairment of caveolin-1 synthesis by H2O2 was not responsible for diminished trafficking. Similarly, the inhibition was independent of H2O2-induced caveolin-1 phosphorylation as shown by the markedly different concentration dependences. We tested the effect of H2O2 on palmitoylation of caveolin-1 by the incorporation of [3H]palmitic acid. Exposure of ECs to H2O2 markedly inhibited the palmitoylation of caveolin-1. Comparable inhibition was observed after treatment of cells with H2O2 delivered either as a bolus or by continuous delivery with glucose and glucose oxidase. Kinetic studies showed that H2O2 did not alter the rate of caveolin-1 depalmitoylation but instead decreased the 'on-rate' of palmitoylation. Together these results show for the first time the modulation of protein palmitoylation by oxidative stress, and suggest a cellular mechanism by which stress might influence caveolin-1-dependent cell activities such as the concentration of signalling proteins and cholesterol trafficking.

NASA Discipline Cell Biology↗

NASA NTRS2000

Hydrogen Biogeochemistry in Anaerobic and Photosynthetic Ecosystems

The simple biochemistry of molecular hydrogen is central to a large number of microbial processes, affecting the interaction of organisms with each other and with the environment. In anoxic sediments, a great majority of microbial redox processes involve hydrogen as a reactant, product or potential by-product. Accordingly, the energetics (thermodynamics) of each of these processes is affected by variations in local H2 concentrations. It has long been established that this effect is important in governing microbe-microbe interactions and there are multiple demonstrations that "interspecies hydrogen transfer" can alter the products of, inhibit/stimulate, or even reverse microbial metabolic reactions. In anoxic sediments, H2 concentrations themselves are thought to be controlled by the thermodynamics of the predominant H2-consuming microbial process. In sediments from Cape Lookout Bight, this relationship quantitatively describes the co-variation of H2 concentrations with temperature (for methanogens and sulfate reducers) and with sulfate concentration (for sulfate reducers). The quantitative aspect is import= for two reasons: 1) it permits the modeling of H2-sensitive biogeochemistry, such as anaerobic methane oxidation or pathways of organic matter remineralization, as a function of environmental controls; 2) for such a relationship to be observed requires that intracellular biochemistry and bioenergetics are being directly expressed in a component of the extracellular medium. H2 could therefore be utilized a non-invasive probe of cellular energetic function in intact microbial ecosystems. Based on the latter principle we have measured down-core profiles of H2 and other relevant physico-chemical parameters in order to calculate the metabolic energy yields (DG) that support microbial metabolism in Cape Lookout Bight sediments. Methanogens in this system apparently function with energy yields significantly smaller than the minimum requirements suggested by pure culture studies. Our recent work has extended the study of hydrogen to cyanobacterial mat communities. The large amounts of reducing power generated during photosynthetic activity carry the potential to contribute a swamping term to the H2 economy of the anaerobic microbial populations within the mat - and thereby to alter the population structure and biogeochemical function of the mat as a whole. In hypersaline microbial mats, we observe a distinct diel cycle in H2 production and a substantial corresponding flux. On an early Earth dominated by microbial mats, this transmission of photosynthetic reducing power may have carried important implications for both biospheric and atmospheric evolution.

Hoehler, Tori M.↗

NASA NTRS1974

Red cell metabolism studies on Skylab

On the basis of these background data, metabolic studies were performed on humans involved in space flight. These studies included the Skylab experiences. The primary purpose of the investigations was to study red cells for: (1) evidences of lipid peroxidation, or (2) changes at various points in the glycolytic pathway. The Skylab missions were an opportunity to study blood samples before, during, and after flight and to compare results with simultaneous controls. No direct evidence that lipid peroxidation had occurred in the red blood cells was apparent in the studies.

Mengel, C. E.↗

NASA NTRS2020

The Potential Effects of Radiation on the Gut-Brain Axis

Humans may be exposed to different types of radiation in their lifetimes, typically in the form of low linear energy transfer (LET) radiation that is, for example, used as a treatment for cancer. In addition, astronauts may be exposed to high LET radiation in outer space. Here, we propose that alterations to the gastrointestinal (GI) microbiota may occur upon exposure to low or high LET radiation, and that these alterations may perturb important relationships that exist between the GI microbiota and human health. For example, the GI microbiota can communicate with the brain via various pathways and molecules, such as the enteric nervous system, the vagus nerve, microbial metabolites, and the immune system. This relationship has been termed the “gut-brain axis”. Alterations to the composition of the GI microbiome can lead to alterations in its functional metabolic output and means of communication, therefore potentially causing downstream cognitive effects. Consequently, studying how radiation can affect this important network of communication could lead to new and critical interventions, as well as prevention strategies. Herein, we review the evidence supporting a relationship between radiation exposure and disruption of the gut-brain axis as well as summarize strategies that may be used to counter the effects of radiation exposure on the GI microbiome.

Carli B. Jones↗

NASA NTRSDate not supplied

LEIA: An Investigation of Radiation Risks to Biology at the Lunar South Pole

Radiation and reduced gravity pose biological risks to crewed deep space exploration. At the cellular level, radiation damage can be amplified by reduced gravity. Empirical evidence on cellular responses to beyond low Earth orbit (BLEO) environments is imperative to develop effective countermeasures for crew health and in-space biomanufacturing. The Lunar Explorer Instrument for Space Biology Applications (LEIA) project is developing an instrument suite to be delivered to the south polar region of the Moon by the Commercial Lunar Payload Services (CLPS) program. This presentation will provide an overview of the LEIA hardware, experiments, and mission timeline. The LEIA instruments include the BioSensor, the ARES charged particle detector, and the Mini-FND. The BioSensor is an autonomous light emitting diode (LED)-based spectrophotometer and microfluidic incubator. The BioSensor activates yeast cultures and can measure cell growth, metabolic activity, and carotenoid production. The ARES is a Timepix-based charged particle radiation detector that measures dose, dose rate, and linear energy transfer spectra. The Mini-FND is a fast neutron detector that measures albedo neutron flux and energy spectra. Combined, these instruments will be used for yeast genetics experiments to quantify growth, metabolism, and synthetic biology-enabled production of human nutrients, while taking real time measurements of biologically relevant radiation exposure on the lunar surface. These data will be used to test the importance of selected DNA damage repair and reactive oxygen species defense pathways in mitigating cellular damage from lunar surface radiation.

Yeast↗

NASA NTRSDate not supplied

LEIA: An Investigation of Radiation Risks to Biology at the Lunar South Pole

Yeast↗