scholarly journals Selective inhibition of glucose oxidation by triethyltin in rat brain in vivo

1970 ◽  
Vol 119 (1) ◽  
pp. 95-102 ◽  
Author(s):  
J. E. Cremer

Results are reported of a comparative study in vivo of the metabolism of [2-14C]-glucose and [1-14C]acetate in brains of rats intoxicated with triethyltin sulphate. The incorporation of 14C from glucose into glutamate, glutamine, γ-aminobutyrate and aspartate was greatly decreased. The incorporation of 14C from acetate into these amino acids was unaffected. The experimental data indicated that the main action of triethyltin was to decrease the rate at which pyruvate formed from glucose is oxidized. Glycolysis was not inhibited. Changes in glucose metabolism in the brain are shown not to be directly due to hypothermia. Some of the advantages of measuring the labelling of intermediates at very short time intervals after the injection of the labelled glucose are demonstrated.

1987 ◽  
Vol 253 (3) ◽  
pp. E317-E321 ◽  
Author(s):  
F. A. Carone ◽  
M. A. Stetler-Stevenson ◽  
V. May ◽  
A. LaBarbera ◽  
G. Flouret

Homogenates of brain, pituitary, liver, lung, ovary, and testes were incubated with [pyro Glu1-3,4-3H]luteinizing hormone-releasing hormone ([3H]LHRH), and the profiles of metabolites generated as a function of time were determined. After 5 min of incubation, 5 was the predominant metabolite in most homogenates. Although the profiles of metabolites varied at different time intervals, metabolites 2, 3, 4, and 5, and in some instances 7 and 9, appeared to form simultaneously and were detectable at 10 min. Neither metabolite 6 nor other larger metabolites formed initially as dominant degradation products. The findings suggest cleavage of LHRH by the simultaneous action of several endopeptidases. After a single vascular transit of [3H]LHRH, metabolites were determined in the venous blood of liver, lung, and brain of rats in vivo. There were no metabolites of [3H]LHRH in venous blood of liver and lung; however, metabolites 2-4 were present in venous blood of the brain. Incubation of rat anterior pituitary cells with [3H]LHRH yielded metabolites 1-4 but not metabolites 5 or 9 as in homogenates. Incubation of [3H]LHRH with porcine follicular granulosa cells resulted in the generation of metabolites 2-7 and 9, similar to the profile in homogenates. Thus, since homogenates contain enzymes of disrupted cells, they do not always reflect mechanisms for in vivo hydrolysis of circulating LHRH. Brain degraded 12.1% of LHRH during a single vascular transit and may account for substantial degradation of the circulating hormone.


2002 ◽  
Vol 35 (3) ◽  
pp. 287-325 ◽  
Author(s):  
Robert G. Shulman ◽  
Fahmeed Hyder ◽  
Douglas L. Rothman

1. Summary 2882. Introduction 2883. Relationship between neuroenergetics and neurotransmitter flux 2944. A model of coupling between neuroenergetics and neurotransmission 2965. Relationship between neuroenergetics and neural spiking frequency 2976. Comparison with previous electrophysiological and fMRI measurements 2987. Contributions of non-oxidative energetics to a primarily oxidative brain 2998. Possible explanation for non-oxidative energetics contributions 3009. A model of total neuronal activity to support cerebral function 30210. Implications for interpretation of fMRI studies 30511. The restless brain 30612. Acknowledgements 31013. Appendix A. CMRO2by13C-MRS 31014. Appendix B.Vcycand test of model 31315. Appendix C. CMRO2by calibrated BOLD 31616. Appendix D. Comparison of spiking activity of a neuronal ensemble with CMRO231817. References 320In vivo13C magnetic resonance spectroscopy (MRS) studies of the brain have quantitatively assessed rates of glutamate–glutamine cycle (Vcyc) and glucose oxidation (CMRGlc(ox)) by detecting 13C label turnover from glucose to glutamate and glutamine. Contrary to expectations from in vitro and ex vivo studies, the in vivo13C-MRS results demonstrate that glutamate recycling is a major metabolic pathway, inseparable from its actions of neurotransmission. Furthermore, both in the awake human and in the anesthetized rat brain, Vcyc and CMRGlc(ox) are stoichiometrically related, where more than two thirds of the energy from glucose oxidation supports events associated with glutamate neurotransmission. The high energy consumption of the brain measured at rest and its quantitative relation to neurotransmission reflects a sizeable activity level for the resting brain. The high activity of the non-stimulated brain, as measured by cerebral metabolic rate of oxygen use (CMRO2), establishes a new neurophysiological basis of cerebral function that leads to reinterpreting functional imaging data because the large baseline signal is commonly discarded in cognitive neuroscience paradigms. Changes in energy consumption (ΔCMRO2%) can also be obtained from magnetic resonance imaging (MRI) experiments, using the blood oxygen level- dependent (BOLD) image contrast, provided that all the separate parameters contributing to the functional MRI (fMRI) signal are measured. The BOLD-derived ΔCMRO2% when compared with alterations in neuronal spiking rate (Δν%) during sensory stimulation in the rat reveals a stoichiometric relationship, in good agreement with 13C-MRS results. Hence fMRI when calibrated so as to provide ΔCMRO2% can provide high spatial resolution evaluation of neuronal activity. Our studies of quantitative measurements of changes in neuroenergetics and neurotransmission reveal that a stimulus does not provoke an arbitrary amount of activity in a localized region, rather a total level of activity is required where the increment is inversely related to the level of activity in the non-stimulated condition. These biophysical experiments have established relationships between energy consumption and neuronal activity that provide novel insights into the nature of brain function and the interpretation of fMRI data.


1964 ◽  
Vol 19 (3) ◽  
pp. 235-248 ◽  
Author(s):  
Benno Parthier

In the green leaves of Nicotiana rustica, protein synthesis of various subcellular fractions has been investigated in vivo after 14CO2-photosynthesis and also in vitro by incorporation of radioactive amino acids. Following photosynthesis, homogenization of the tissues, and differential centrifugation of the homogenates, the results show that all structural particles of the cell are able to use photosynthetically formed amino acids for the incorporation into their proteins. The proteins with the highest specific activities are found in the mitochondria-rich fractions, and with the lowest in the soluble cytoplasma supernatant. High specific activities are also observed in the ribosomal-rich fraction in short-time experiments, and also in the chloroplasts after exposure of the leaves to light. After an osmotic-mechanical destruction of the isolated 14C-labelled chloroplasts, the specific activities of lamellar proteins exceed the colourless soluble proteins of the chloroplasts. A green fraction, sedimented at 1,000 g, and perhaps mainly consisting of broken and leached chloroplasts, shows the highest specific activity of all chloroplast fractions. Obviously, due to the destruction of the natural cell organization, in vitro experiments give not only drastically decreased specific activities but also another distribution of the incorporated amino acids between the subcellular fractions, compared with experiments in vivo.


The cerebral influx rates of fifteen amino acids were measured directly in living rats by means of a new technique which makes it possible to maintain a constant specific activity of a radioactively labelled amino acid in the bloodstream. A wide variation in the influx rates of the amino acids was found. These rates differed from those found by other workers using in vitro preparations, but are consistent with the theory that amino acids enter the brain mainly by carrier mediated transport processes with a high degree of specificity. There are a number of important differences between the behaviour of the transport processes in vivo and in vitro . The influx rates of the various amino acids were directly proportional to their concentra­tions in blood plasma (over the range of concentrations studied). All the nutritionally essential amino acids had relatively high influx rates as did other amino acids which the brain does not seem to be able to synthesize. On the other hand, amino acids that the brain can readily synthesize and two amino acids which are not normally found in mammalian tissues had low influx rates.


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