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R W Guynn

Publications and source records attributed to R W Guynn.

17 recordsLinked to original sources
PubMed1979

The effect of the combination of lithium and haloperidol on brain intermediary metabolism in vivo.

The effect of the chronic administration of the combination of lithium and haloperidol has been studied in rat brain in vivo. Lithium was administered in food in amounts sufficient to maintain serum lithium levels of 1.0 +/- 0.1 mEq/l; haloperidol (1.5 mg/kg) was given i.p. once daily. Control animals pair-fed with the lithium/haloperidol alone, or neither drug. Fifteen days after the beginning of the experiments the brains were instantaneously frozen with a rapid brain-freezing device and multiple metabolites were measured in the perchloric acid extract of the tissue. Intermediates examined included selected metabolites of the glycolytic pathway and the tricarboxylic acid cycle, N-acetylaspartate and cofactors such as ATP, CoA, and acetyl-CoA. Estimates of the effects of the treatments on cytoplasmic and mitochondrial redox states were also made. The results showed only minor effects of any of the treatments on any of the parameters studied and little or nothing to distinguish the combination of lithium and haloperidol from either treatment alone.

Animals↗
PubMed1978

Organic fluorides: implications for psychiatry.

The widespread use of synthetic organic fluorides has recently received attention as a potential health hazard. There are a number of organic fluorides which have become important considerations in psychiatry. Therapeutically the organic fluorides include the neuroleptics trifluoperazine, fluphenazine, triflupromazine, and haloperidol, the benzodiazepine flurazepam and the polyfluorinated inhalant convulsant indoklon. On the negative side, deliberate inhalation of fluorocarbon aerosol propellants has become a modern form of drug abuse among the young. A review is presented on the biochemistry and toxicology of organic fluorides with special emphasis on implications to the field of psychiatry.

Aerosols↗
PubMed1976

Equilibrium constants under physiological conditions for the reactions of choline kinase and the hydrolysis of phosphorylcholine to choline and inorganic phosphate.

The observed equilibrium constants (Kobs) of the P-choline hydrolysis reaction have been determined under physiological conditions of temperature (38 degrees) and ionic strength (0.25 M) and physiological ranges of pH and free [Mg2+]. Using sigma and square brackets to indicate total concentrations: (see article.) The value of Kobs has been found to be relatively insensitive to variations in pH and free [Mg2+]. At pH 7.0 and taking the standard state of liquid water to have unit activity ([H2O] = 1), Kobs = 26.6 M at free [Mg2+] = 0 [epsilon G0obs = -2.03 kcal/mol(-8.48 kJ/mol)], 26.8 M at free [Mg2+] = 10(-3) M, and 28.4 M at free [Mg2+] = 10(-2) M. At pH 8.0, Kobs = 18.8 M at free [Mg2+] = 0, 19.2 M at free [Mg2+] = 10(-3), and 22.2 M at free [Mg2+] = 10(-2) M. These values apply only to situations where choline and Pi concentrations are both relatively low (such as the conditions found in most tissues). At higher concentrations of phosphate and choline, the value of Kobs becomes significantly increased since HPO42- complexes choline weakly (association constant = 3.3 M-1). The value of K at 38 degrees and I = 0.25 M is calculated to be 16.4 +/- 0.3 M [epsilonG0 = 1.73 kcal/mol (-7.23 kJ/mol)]. The K for the P-choline hydrolysis reaction has been combined with the K for the ATP hydrolysis reaction determined previously under physiological conditions to calculate a value of 4.95 X 10(-3 M [deltaG0 j.28 kcal/mol (13.7 kJ/mol] for the K of the choline kinase reaction (EC 2.7.1.32), an important step in phospholipid metabolism: (see article.) Likewise, values for Kobs for the choline kinase reaction at 38 degrees, pH 7.0, and I = 0.25 M have been calculated to be 5.76 X 10(4) [deltaG0OBS = -6.77 KCAL/MOL (-28.3 KJ/mol)] at [Mg2+] = 0; 1.24 X 10(4) [deltaG0obs = -5.82 kcal/mol (-24.4 kJ/mol)] at [Mg2+] = 10(-3) M and 8.05 X 10(3) [delta G0obs = -5.56 kcal/mol (-23.3 kJ/mol)] at [Mg2+ = 10(-2) M. Attempts to determine the Kobs of the choline kinase reaction directly were unsuccessful because of the high value of the constant. The results indicate that in contrast to the high deltaG0obs for the hydrolysis of the ester bond of acetylcholine, the deltaG0obs for the hydrolysis of the ester bond of P-choline is quite low, among the lowest known for phosphate ester bonds of biological interest.

Binding Sites↗
PubMed1975

Equilibrium constants of the reactions of choline acetyltransferase, carnitine acetyltransferase, and acetylcholinesterase under physiological conditions.

The observed equilibrium constant (Kobs) for the reaction of choline acetyltransferase (EC 2.3.1.6) has been determined under physiological conditions. Using sigma and square brackets to indicate total concentrations of all ionic species present: (see article). The value of Kobs has been determined to be 12.3 plus or minus 0.6 at 38 degrees, pH 7.0 and ionic strength 0.25 M. The value at 25 degrees is not significantly different, and the constant has been found to be insensitive to variations in ionic strength (0.03 to 0.375 M), pH (6.5 TO 7.5) OR FREE [Mg-2+] (0 to 5 mM). The Kobs of this reaction reflects the difference between the observed standard free energy change (delta G-oobs) for the hydrolysis of acetylcholine and the delta G-oobs for the hydrolysis of acetyl-CoA. Since the delta G-oobs for the hydrolysis of acetyl-CoA has been previously determined to be minus 8.54 kcal/mol (minus 35.75 kJ/mol under the same physiological conditions, the delta G-oobs for the reaction of acetylcholinesterase (EC 3.1.1.7): (SEE ARTICLE). Can be calculated to be minus 6.99 kcal/mol (minus 29.26 kJ/mol) at pH ionic strength 0.25 M and 38 degrees, taking the standard state of liquid water to have unit activity ([H2O] equals 1). The pKa for acetic acid under the same conditions, has been determined to be 4.60 plus or minus 0.01, allowing the Kobs for the pH-independent reaction (see article). To be calculated to be 3.28 times 10-2 M. Choline and carnitine are chemical analogues. The Kobs for the corresponding reaction of carnitine acetyltransferase (EC 2.3.1.7). (SEE ARTICLE). Under the same physiological conditions of pH (7.0), ionic strength (0.25 M), and temperature (38 degrees) has been determined to be 1.73 plus or minus 0.05, making the delta G-oobs for the hydrolysis of acetylcholine only 1.21 kcal/mol (5.06 kJ) less negative than that for the hydrolysis of acetylcarnitine.

Acetyl Coenzyme A↗
PubMed1975

Dependence on dose of the acute effects of ethanol on liver metabolism in vivo.

The dose dependence of the acute effects of ethanol upon liver intermediary metabolism in vivo has been demonstrated in rats. Ethanol was given i.p. in doses of 0.69, 1.7, and 3.0 g/kg in equal volumes (20 ml/kg). The liver was freeze-clamped 120 min after injection, and multiple metabolites were measured in the perchloric acid extract of the tissue. Each group showed a significantly different pattern of metabolites, redox states, and phosphorylation potentials although the rate of ethanol disappearance, at least between the two highest dose groups, was not significantly different. The mitochondrial free [NAD+]/[NADH] ratios and the cytoplasmic free [NADP+]/[NADPH] ratio were paradoxically most reduced with the lowest dose of ethanol and became progressively more oxidized with increasing dose. Once established, the differences in these ratios between the groups tended to persist with time, relatively independent of the concentration of ethanol. In a somewhat different pattern, the phosphorylation potential ([ATP]/[ADP][P1]) remained at the control level in the low-dose group but was significantly elevated in the two higher-dose groups. The results, therefore, show distinct and complicated dose-dependent patterns of intermediary metabolism that cannot be explained completely by any one hypothesis but that imply significant dose-dependent effects of ethanol upon intermediary metabolism not directly related to NADH production.

Adenosine Triphosphate↗