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Biomedical subjects

F F Brown

Publications and source records attributed to F F Brown.

9 recordsLinked to original sources
PubMed1979

Proton nuclear magnetic resonance studies on bovine lutropin, its subunits, and on the alpha subunit of pregnant mare serum gonadotropin. Assignment of histidine resonances in the alpha subunit.

The pK values of the 3 histidine residues in the common alpha subunits of bovine and equine glycoprotein hormones have been determined from titration curves generated from their C-2 proton nuclear magnetic resonances at different pH values. Assignment of resonances to specific histidines is based on a comparison between the two species, which have 1 histidine residue in different positions in their sequences, and of the bovine alpha subunit after removal of its histidine 94 by treatment with carboxypeptidases. In both species, those histidines closest to the COOH terminus titrate with near normal pK values of 6.2. The histidine residue found in the bovine subunit at position 87 titrates with an approximate pK value of 5.4. Histidine 83, adjacent to an oligosaccharide moiety in both species, does not titrate over a pH range of 4.0 to 8.0 and thus appears inaccessible to solvent. Similarly, in bovine lutropin-beta, 1 of 3 histidine residues does not titrate between pH 5.0 and 7.0. In the intact hormone, 2 "nontitratable" histidine residues are found. Changes in the characteristics of the signals, however, preclude unambiguous assignment of these two resonances to the nontitrating histidines in the isolated subunits. It appears that changes in the environment of at least some histidines occur when the subunits combine to yield intact hormone.

Amino Acid Sequence↗
PubMed1979

Application of spin-echo nuclear magnetic resonance to whole-cell systems. Membrane transport.

A new method for studying membrane transport is presented. High resolution n.m.r. is used to measure the distribution of small molecules between the intracellular and extracellular compartments. The method uses spin-echo techniques and relies on a difference in the magnetic susceptibility of the media inside and outside of cells. It also provides simultaneous information on the metabolic status of the cell. The method is illustrated by a study of alanine and lactate transport in the human erythrocyte.

Alanine↗
PubMed1978

Volatile anesthetic facilitation of in vitro desensitization of membrane-bound acetylcholine receptor from Torpedo californica.

Incubation of membrane fragments bearing acetylcholine receptors from Torpedo californica under an atmosphere of 3% halothane, 1% chloroform, or 6% diethyl ether greatly facilitates the carbamoylcholine-induced structural transition of the acetylcholine receptor reflected by alterations in the rate of binding of (125)I-labeled alpha-bungarotoxin. The half-time of this ligand-induced conformational change is decreased to 10% of the original value after incubation of the membranes with these volatile anesthetics at or near their clinical concentrations. The synergistic effects observed with the general anesthetics and carbamoylcholine are abolished if the membranes are incubated under a stream of air after exposure to the inhalational agents. The antagonist d-tubocurarine exerts a smaller yet measurable time-dependent effect on the toxin-binding properties of the membrane fragments. Treatment of membranes with general anesthetics facilitates this antagonist-induced conversion of the receptor protein as well. The synergism between ligands and general anesthetics may be due to the disruption by these inhalational agents of interactions at the protein-lipid interface, which may play a significant role in determination of receptor conformation. In addition, if the conformational change induced by carbamoylcholine observed in the snake toxin binding assay corresponds to desensitization of the receptor in vivo, facilitation of this conformational change by volatile anesthetics provides an attractive model for the pharmacological action of these compounds.

Anesthetics↗
PubMed1977

Perturbations of model protein systems as a basis for the central and peripheral mechanisms of general anaesthesia.

Protein perturbations associated with anaesthetic interactions are relevant to: (a) the central molecular mechanisms of general anaesthesia; (b) the molecular basis of physiological selectivity and anaesthetic specificity of the many 'side-effects' of anaesthesia; (c) the use of anaesthetic agents as selective hydrophobic probes for the study of protein structures and activities in detail. Small but specific protein perturbations have been studied with various nuclear magnetic resonance procedures with haemoglobin as a model protein to establish the 'ground-rules' for anaesthetic-macromolecule interactions. The correlation of one aspect of these perturbations with anaesthetic potency and hydrophobic solubility indicates that hydrophobic pockets in proteins can behave like bulk-lipid phases in terms of their solubility characteristics. Other aspects appear to depend on physical characteristics such as size, geometry, structure and composition of the individual agents. These data support the hypothesis that anaesthetic actions can be explained on a molecular basis by direct interactions with proteins in addition to lipid and aqueous effects.

Anesthesia, General↗
PubMed1977

The interaction of some bis-arylhydroxysulphonic acids with a site of known structure in human haemoglobin.

1 Two bis-arylhydroxysulphonic acids were previously designed to interact with the known molecular configuration of the 2,3-diphosphoglycerate (DPG) receptor-site of human haemoglobin. These compounds liberate oxygen from the haemoglobin similarly to DPG. 2 Solutions of haemoglobin have now been observed under physiological conditions by nuclear magnetic resonance (n.m.r.) in the presence of DPG and of the compounds. 3 Two peaks in the n.m.r. spectrum of haemoglobin are shifted when DPG is added to the solution. 4 The same two peaks in the spectrum are affected by the compounds. 5 The observations are compatible with the predicted interaction between the compounds and the haemoglobin receptor site.

Arylsulfonates↗
PubMed1975

Nuclear magnetic resonance studies of anaesthetic interactions with haemoglobin.

The use of 270 MHz Fourier Transform nuclear magnetic resonance (NMR) spectrometer, combined with signal processing techniques to improve resolution, enabled proton resonances from the individual aromatic residues of haemoglobin to be distinguished. In the presence of clinical concentrations of the general anaesthetic drugs halothane and methoxyflurane, specific changes in the NMR spectrum can be distinguished which probably reflect local changes of conformation. When higher concentrations of anaesthetic are used, extensive changes in the NMR spectrum occur which are consistent with non-specific binding of the anaesthetic to the hydrophobic parts of the haemoglobin molecule.

Chemical Phenomena↗