Glucose and Intermediary Metabolism of the Lungs

Tierney, Donald F.; Young, Stephen L.

doi:10.1002/cphy.cp030106

Cited by 7 publications

(7 citation statements)

References 101 publications

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“…For most tissues, glucose serves as the primary source of energy, and this is also true for the lung (6). In fact, glucose oxidation has been estimated to be 40–50 μmol/(h·g) of dry lung weight, which is a value equal to or greater than most other metabolically active organs (7, 8). The metabolism of glucose begins with a 10-step reaction in the cytoplasm known as glycolysis, or more formally called the glycolytic pathway.…”

Section: Cellular Metabolism and Its Major Pathwaysmentioning

confidence: 99%

“…This is further compounded by the fact that turnover of surfactant phospholipids in the lung is exceedingly high. For example, Tierney and colleagues (8, 30) showed that the half-life of disaturated phosphatidylcholine is only 14 h in the healthy rat lung, and others have reported similar or even more rapid turnover rates in the newborn human lung and in injured rodent lung tissues (31). Because fatty acid synthesis is not feasible under a number of conditions (e.g., high intracellular AMP/ATP ratios), type II cells have evolved to utilize other less energy-costly methods for replenishing their surfactant lipid pool.…”

Section: Lipid Synthesis In Lungmentioning

confidence: 99%

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Cellular Metabolism in Lung Health and Disease

Liu

Summer

2019

Annu. Rev. Physiol.

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The lung is often overlooked as a metabolically active organ, yet biochemical studies have long demonstrated that glucose utilization surpasses that of many other organs, including the heart, kidney, and brain. For most cells in the lung, energy consumption is relegated to performing common cellular tasks, like mRNA transcription and protein translation. However, certain lung cell populations engage in more specialized types of energy-consuming behaviors, such as the beating of cilia or the production of surfactant. While many extrapulmonary diseases are now linked to abnormalities in cellular metabolism, the pulmonary community has only recently embraced the concept of metabolic dysfunction as a driver of respiratory pathology. Herein, we provide an overview of the major metabolic pathways in the lung and discuss how cells sense and adapt to low-energy states. Moreover, we review some of the emerging evidence that links alterations in cellular metabolism to the pathobiology of several common respiratory diseases.

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Section: Cellular Metabolism and Its Major Pathwaysmentioning

confidence: 99%

Section: Lipid Synthesis In Lungmentioning

confidence: 99%

Cellular Metabolism in Lung Health and Disease

Liu

Summer

2019

Annu. Rev. Physiol.

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“…[1-14 C]CO 2 is released via the pentose phosphate pathway as well as via the tricarboxylic acid pathway, while [6-14 C]CO 2 is released by the tricarboxylic acid cycle only. Thus the activity of the HMS may be assessed by subtracting the radioactivity trapped when incubating with [6-14 C]glucose from that trapped when incubating with [1-14 C]glucose (Fisher and Reicherter 1984;Tierney and Young 1992). This was carried out in the initial experiments, but in this paper HMS has been calculated from dpm-values after incubation with [1-14 C]glucose only, because in the ®rst series of experiments we noticed that 14 CO 2 produced by incubating with [6-14 C]glucose was quite stable and always much lower than the 14 CO 2 produced from [1-14 C]glucose, as has been found by other authors (Holian and Daniele 1981).…”

Section: Cell Treatment and Determination Of Hms Activitymentioning

confidence: 99%

Activation of the hexose monophosphate shunt in rat type II pneumocytes as an early marker of oxidative stress caused by cobalt particles

et al. 2002

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Cobalt metal (mCo) and hard metal, a mixture of cobalt and tungsten carbide (CoWC), are cytotoxic for alveolar macrophages and alveolar type II cells (AT-II). Although the exact mechanisms of toxicity are not entirely elucidated, evidence exists for an oxidant-mediated toxicity. In this study, we exposed primary cultures of rat AT-II, in vitro, to different forms of cobalt (mCo particles, CoWC particles, CoCl(2)) and assessed changes in the activity of the hexose monophosphate shunt (HMS). Activation of the HMS occurs as an early response to (per)oxidative stress. Cobalt metal-containing particles (mCo and CoWC) when freshly immersed in medium, lead to an early concentration-dependent stimulation of the HMS in rat AT-II. The maximum stimulations of HMS (reached after 90 min) were 2.0 +/-1.2, 2.9+/-0.4, 3.3 +/-1.6 and 4.0+/-0.4 fold-increases for 15, 75, 300 and 1200 microg mCo/well, respectively. The observed time course of the activation by mCo particles clearly differed from that caused by paraquat (10(-5 )M), which is known to produce activated oxygen species after cyclic oxidation-reduction reactions. The comparable effect of peroxides (H2O2 and t-butyl hydroperoxide) on HMS and the inhibitory effects of catalase on the mCo-induced stimulation of the HMS strongly suggest the production of peroxides by freshly immersed mCo particles. However, we were not able to show a simple relationship between the stimulation of the HMS and the subsequent cell damage.

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“…those present before the hyperpolarized agent is injected) are determined by the balance of this production and transport to and from the extracellular space. The rate of glucose consumption is significantly affected by intracellular lactate and pyruvate concentrations, as well as their ratio ; however, we do not find it necessary to include these effects in the present treatment, because at high metabolite concentrations, where the effect is most pronounced, glycolytic activity becomes increasingly irrelevant to the overall rate of NAD oxidation and reduction.…”

Section: Introductionmentioning

confidence: 98%

The effect of exogenous substrate concentrations on true and apparent metabolism of hyperpolarized pyruvate in the isolated perfused lung

et al. 2014

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Although relatively metabolically inactive, the lung has an important role in maintaining systemic glycolytic intermediate and cytosolic redox balance. Failure to perform this function appropriately may lead to lung disease progression, including systemic aspects of these disorders. In this study, we experimentally probe the response of the isolated, perfused organ to varying glycolytic intermediate (pyruvate and lactate) concentrations, and the effect on the apparent metabolism of hyperpolarized 1-13C pyruvate. Twenty four separate conditions were studied, from sub-physiological to super-physiological concentrations of each metabolite. A three-compartment model is developed, which accurately matches the full range of experiments and includes a full accounting for evolution of agent concentration and polarization. The model is then refined using a series of approximations which are shown to be applicable to cases of physiological relevance, and which facilitate an intuitive understanding of the saturation and scaling behavior. Perturbations of the model assumptions are used to determine the sensitivity to input parameter estimates, and finally the model is used to examine the relationship between measurements accessible by NMR and the underlying physiological parameters of interest. Based on the observed scaling of lactate labeling with lactate and pyruvate concentrations, we conclude that the level of hyperpolarized lactate signal in the lung is primarily determined by the rate at which NAD+ is reduced to NADH. Further, although weak dependencies on other factors are predicted, the modeled NAD+ reduction rate is largely governed by the intracellular lactate pool size. Conditions affecting the lactate pool can therefore be expected to display the highest contrast in hyperpolarized 13C-pyruvate imaging. The work is intended to serve as a basis to interpret both the signal dynamics of hyperpolarized measurements in the normal lung, and to understand the cause of alternations seen in a variety of disease and exposure models.

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Glucose and Intermediary Metabolism of the Lungs

Cited by 7 publications

References 101 publications

Cellular Metabolism in Lung Health and Disease

Cellular Metabolism in Lung Health and Disease

Activation of the hexose monophosphate shunt in rat type II pneumocytes as an early marker of oxidative stress caused by cobalt particles

The effect of exogenous substrate concentrations on true and apparent metabolism of hyperpolarized pyruvate in the isolated perfused lung

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