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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    The @journal of physical chemistry 〈Washington, DC〉 64 (1960), S. 376-377 
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 55 (1990), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: 3-O-Methyl-d-glucose (methylglucose) is often used to study blood-brain barrier transport and the distribution spaces of hexoses in brain. A critical requirement of this application is that it not be chemically converted in the tissues. Recent reports of phosphorylation of methylglucose by yeast and heart hexokinase have raised questions about its metabolic stability in brain. Therefore, we have re-examined this question by studying the metabolism of methylglucose by yeast hexokinase and rat brain homogenates in vitro and rat brain, heart, and liver in vivo. Commercial preparations of yeast hexokinase did convert methylglucose to acidic products, but only when the enzyme was present in very large amounts. Methylglucose was not phosphorylated by brain homogenates under conditions that converted 97% of [U-14C]glucose to ionic derivatives. When [14C]methylglucose, labeled in either the methyl or glucose moiety, was administered to rats by an intravenous pulse or a programmed infusion that maintained the arterial concentration constant and total 14C was extracted from the tissues 60 min later, 97–100% of the 14C in brain, 〉99% of the 14C in plasma, and 〉90% of that in heart and liver were recovered as unmetabolized [14C]methylglucose. Small amounts of 14C in brain (1–3%), heart (3–6%), and liver (4–7%) were recovered in acidic products. Plasma glucose levels ranging from hypoglycemia to hyperglycemia had little influence on the degree of this conversion. The distribution spaces for methylglucose were found to be 0.52 in brain and heart and 0.75 in liver.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 51 (1988), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: An antibody that inhibits over 95% of the cytosolic NADP+-dependent 7-hydroxybutyrate (GHB) dehydrogenase activity of either rat brain or kidney was found to inhibit only approximately 50% of the conversion of [1–14C]GHB to 14CO2 by rat kidney homogenate. A similar result was obtained with sodium valproate, a potent inhibitor of GHB dehydrogenase. The mitochondrial fraction from rat brain and kidney was found to catalyze the conversion of [1–14C]GHB to 14CO2. The dialyzed mitochondrial fraction also catalyzed the oxidation of GHB to succinic semialdehyde (SSA) in a reaction that did not require added NAD+ or NADPT and which was not inhibited by sodium valproate. The enzyme from the mitochondrial fraction which converts GHB to SSA appears to be distinct from the NADP+-depen-dent cytosolic oxidoreductase which catalyzes this reaction.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The observations made by Sacks et al. [Neurochem. Rea.8, 661–685 (1983)] on which they based their criticisms of the deoxyglucose method have been examined and found to have no relationship to the conclusions drawn by them. (1) The observations of Sacks et al. (1983) of constant concentrations of [14C]deoxyglucose and [14C]deoxyglucose-6-phosphate. predominantly in the form of product, reflects only the postmortem phosphorylation of the precursor during the dissection of the brain in their experiments. When the brains are removed by freeze-blowing, the time courses of the [14C]deoxyglucose and [14C]deoxyglucose-6-phos-phate concentrations in brain during the 45 min after the intravenous pulse are close to those predicted by the model of the deoxyglucose method. (2) Their observation of a reversal of the cerebral arteriovenous difference from positive to negative for [14C]deoxyglucose and not for [14C]glucose after an intravenous infusion of either tracer is, contrary to their conclusions, not a reflection of glucose-6-phosphatase activity in brain but the consequence of the different proportions of the rate constants for efflux and phosphorylation for these two hexoses in brain and is fully predicted by the model of the deoxyglucose method. (3) It is experimentally demonstrated that there is no significant arteriovenous difference for glucose-6-phosphate in brain, that infusion of [12P]glucose-6-phosphate results in no labeling of brain, and that the blood-brain barrier is impermeable to glucose-6-phosphate. Glucose-6-phosphate cannot, therefore, cross the blood-brain barrier, and the observation by Sacks and coworkers [J. Appl. Physiol.24, 817–827 (1968); Neuro-chein. Res.8, 661–685 (1983)J of a positive cerebral arteriovenous difference for [14C]glucose-6-phosphate and a negative arteriovenous difference for [14C]glucose cannot possibly reflect glucose-6-phosphatase activity in brain as concluded by them. Each of the criticisms raised by Sacks et al. has been demonstrated to be devoid of validity.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The time course and magnitude of the effects of product loss on the measurement of local cerebral glucose utilization (LCGU) by the 2-[14C]deoxyglucose (DG) method were studied by determination of LCGU in 38 rats with 25–120 min experimental periods after a [14C]DG pulse and in 45 rats with experimental periods of 2.5–120 min during which arterial plasma [14C]DG concentrations (CP*) were maintained constant. LCGU was calculated by the operational equation, which assumes no product loss, with the original set of rate constants and with a new set redetermined in the rats used in the present study; in each case the rate constants were those specific to the structure. Data on local tissue 14C concentrations and CP* were also plotted according to the multiple time/graphic evaluation technique (“Patlak Plot”). The results show that with both pulse and constant arterial inputs of [14C]DG the influence of the rate constants is critical early after onset of tracer administration but diminishes with time and becomes relatively minor by 30 min. After a [14C]DG pulse calculated LCGU remains constant between 25 and 45 min, indicating a negligible effect of product loss during that period; at 60 min it begins to fall and declines progressively with increasing time, indicating that product loss has become significant. When CP* is maintained constant, calculated LCGU does not change significantly over the full 120 min. The “Patlak Plots” reinforced the conclusions drawn from the time courses of calculated LCGU; evidence for loss of product was undetectable for at least 45 min after a pulse of [14C]DG and for at least 60 min after onset of a constant arterial input of [14C]DG.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 48 (1987), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The concentration of γ-hydroxybutyrate (GHB) in brain, kidney, and muscle as well as the clearance of [1-14C]GHB in plasma have been found to be altered by the administration of a number of metabolic intermediates and drugs that inhibit the NADP+-dependent oxidoreductase, “GHB dehydrogenase,” an enzyme that catalyzes the oxidation of GHB to succinic semialdehyde. Administration of valproate, salicylate, and phenylacetate, all inhibitors of GHB dehydrogenase, significantly increased the concentration of GHB in brain; salicylate increased GHB concentration in kidney, and α-ketoisocaproate increased GHB levels in kidney and muscle. The half-life of [1-14C]GHB in plasma was decreased by D-glucuronate, a compound that stimulates the oxidation of GHB by this enzyme and was increased by a competitive substrate of the enzyme, L-gulonate. The results of these experiments suggest a role for GHB dehydrogenase in the regulation of tissue levels of endogenous GHB.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Journal of neurochemistry 43 (1984), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: The incorporation of 14C into glycogen in rat brain has been measured under the same conditions that exist during the measurement of local cerebral glucose utilization by the autoradiographic 2-[14C]deoxyglucose method. The results demonstrate that approximately 2% of the total 14C in brain 45 min after the pulse of 2-[14C]deoxyglucose is contained in the glycogen portion, and, in fact, incorporated into α-1-4 and α-1-6 deoxyglucosyl linkages. When the brain is removed by dissection, as is routinely done in the course of the procedure of the 2-[14C]deoxyglucose method to preserve the structure of the brain for autoradiography, the portion of total brain 14C contained in glycogen falls to less than 1%, presumably because of postmortem glycogenolysis which restores much of the label to deoxyglucose-phosphates. In any case, the incorporation of the 14C into glycogen is of no consequence to the validity of the autoradiographic deoxyglucose method, not because of its small magnitude, but because 2-[14C]deoxyglucose is incorporated into glycogen via [14C]deoxyglucose-6-phosphate, and the label in glycogen represents, therefore, an additional “trapped” product of deoxyglucose phosphorylation by hexokinase. With the autoradiographic 2-[14C]deoxyglucose method, in which only total 14C concentration in the brain tissue is measured by quantitative autoradiography, it is essential that all the labeled products derived directly or indirectly from [14C]deoxyglucose phosphorylation by hexokinase be retained in the tissue; their chemical identity is of no significance.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract— An NADP+ -linked enzyme, capable of interconverting γ-hydroxybutyrate and succinic semialdehyde, has been isolated from hamster liver and brain. The enzyme which was isolated from liver has been purified 300-fold and exhibits a single band by polyacrylamide gel electrophoresis. The molecular weight of the enzyme is - 31,000 as estimated from gel filtration and 38,000 as estimated from sodium dodccyl sulfate gel electrophoresis. The enzyme is inhibited by amobarbital, diphenylhy-dantoin, 2-propylvalerate, and diethyldithiocarbamate, but not by pyrazole. The enzymes from brain and liver appear to be very similar with regard to their molecular weights and their kinetic constants for γ-hydroxybutyrate and succinic semialdehyde.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Industrial & engineering chemistry research 27 (1988), S. 1502-1505 
    ISSN: 1520-5045
    Source: ACS Legacy Archives
    Topics: Chemistry and Pharmacology , Process Engineering, Biotechnology, Nutrition Technology
    Type of Medium: Electronic Resource
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