Search PubMed⌕ Search

Biomedical subjects

W D Brown

Publications and source records attributed to W D Brown.

At least 73 records · Page 4Linked to original sources
PubMed1987

Body burden profiles of single and mixed solvent exposures.

The dynamics of inhaled solvents have not been studied extensively for exposure conditions involving combinations of chemical agents. An ongoing laboratory study examining psychomotor performance effects on human volunteers exposed to spray paint agents offered an opportunity to gather data on the body burden profiles produced by the inhalation of two solvents alone and in combination. Breath and blood samples were collected from 70 male and female subjects who were randomly assigned to four treatment conditions: chemical placebo, 250 ppm acetone, 200 ppm methyl ethyl ketone, or 125 ppm acetone/100 ppm methyl ethyl ketone. The exposures lasted for four hours. No interaction between the two solvents affecting uptake or elimination was noted. There were no significant differences between the uptake and elimination in males and females. The results are discussed in relation to physiological simulation modeling of the exposure.

Acetone↗
PubMed1986

Myoglobin interspecies structural differences: effects on autoxidation and oxygenation.

Thermodynamic and kinetic parameters of the oxygenation and autoxidation reactions were determined for yellowfin tuna (Thunnus albacares), Pacific green sea turtle (Chelonia mydas caranigra), and sperm whale myoglobin. These proteins have quite similar heme contact residues, but vary in residues which are involved in globin stabilization and in postulated ligand paths to the heme iron. Oxygen equilibria measurements from 10 to 40 degrees C reveal that green sea turtle myoglobin has a lower oxygen affinity and lower enthalpy and entropy for oxygen-binding than the other proteins. Yellowfin tuna myoglobin has the most rapid oxygen dissociation rate and the highest susceptibility to autoxidation under all conditions studied. However, the dependence of the autoxidation rate on ionic strength is the same for the three proteins, despite substantial differences in their dynamic stabilities. These results suggest that the autoxidation reaction is more dependent on ligand accessibility than on the dynamic stability of the myoglobin.

Animals↗
PubMed1985

Myoglobin: cytochrome b5 interactions and the kinetic mechanism of metmyoglobin reductase.

Metmyoglobin (metMb) reduction by metMb reductase from heart muscle requires cytochrome b5 as electron-transfer mediator. The existence of a metMb-ferrous cytochrome b5 complex is demonstrated by mutual perturbation of the proteins' respective electrophoretic titration curves between pH 4 and 7. The same technique shows a preferential binding of cytochrome b5 over metMb by the enzyme. The paramagnetic hyperfine shifts in the cytochrome b5 1H NMR spectrum are perturbed by metMb, indicating the formation of a specific bimolecular complex with a 1:1 stoichiometry and a binding constant estimated to be less than 10 microM. The resonances assigned to the cytochrome b5 heme 6-propionate methylene group exhibit the largest complexation shifts. Computer modeling implicates lysines 47, 50, and 98 of metMb as contact points with cytochrome b5 carboxylate residues 43, 44, 60, and heme 6-propionate. The mechanism of the enzymatic reduction establishes metMb reductase as an NADH-cytochrome b5 oxidoreductase. Cytochrome b5 is reduced at near diffusion-controlled rates by the enzyme with a turnover number of 1000 min-1 X Km for the cytochrome is 0.9 microM versus 100 microM reported for the erythrocyte enzyme. Ferrous cytochrome b5 then reduces metMb nonenzymatically with an apparent rate constant of 4.9 X 10(4) M-1 min-1 X Acetylation of metMb, which does not affect its oxygen affinity or chemical reduction, renders it a poor substrate for enzymatic reduction. This study suggests a function for the three exterior lysine residues conserved in all mammalian myoglobin sequences: they are contact points for complexation with cytochrome b5.

Acetylation↗
PubMed1985

Proton NMR study of yellowfin tuna myoglobin in whole muscle and solution. Evidence for functional metastable protein forms involving heme orientational disorder.

Proton NMR spectra of met-aquo-myoglobin have been recorded in whole dark muscle from yellowfin tuna for the first time; in addition, spectra of the met-aquo, met-cyano, and deoxy forms were recorded in solution. The number of resolved methyl resonances in the met-aquo and met-cyano derivatives of the purified protein indicates a molecular heterogeneity, with the two species present in a ratio of approximately 3:2. These same two species, in very similar environments, are found in whole muscle. Upon reconstitution of the protein, the ratio of the two species is approximately 1:1. Specific isotope labeling in the met-cyano form reveals an interchange of 5-methyl and 8-methyl environments that is characteristic of heme orientational disorder about the alpha, gamma-meso axis. Incubation of the met-cyano protein at 37 degrees C shows that the two species are interconvertible, with the minor component declining to about one-eighth of that of the major component. This indicates that one of the two orientations is favored thermodynamically. The rate of equilibration for the met-aquo protein is exceedingly slow (half-life greater than 30 days), some 10(2) slower than for the analogous sperm whale derivative. The "reversed" heme orientation is therefore present in muscle as a kinetically trapped or metastable species, suggesting that the last step in the biosynthesis of myoglobin is similar to that of in vitro reconstitution. The presence of both heme orientations in myoglobin in whole muscle proves that heme orientational disorder is a physiological phenomenon.

Amino Acid Sequence↗
PubMed1985

Isolation and characterization of metmyoglobin reductase from yellowfin tuna (Thunnus albacares).

The isolation, purification, and characterization of metmyoglobin reductase from yellowfin tuna (Thunnus albacares) is described. The enzyme has been purified 120-fold. Characterization of the enzyme includes molecular weight, isoelectric point, substrate specificity, enzyme kinetics, chromatographic behavior, and sensitivity to inhibitors. The physical and catalytic properties of the tuna enzyme are compared to those of bovine and blue-white dolphin metmyoglobin reductase.

Animals↗
PubMed1984

A subject index for occupational medical literature.

A subject classification system for organizing files of occupational medical literature is described. In the hierarchical system, based on a textbook integrated index, each subject is assigned a numerical code and articles are coded for filing. Computerized management of the file is discussed.

Abstracting and Indexing↗
PubMed1983

Myoglobin diffusion in bovine heart muscle.

The rotational mobility of myoglobin in situ was determined by proton nuclear magnetic resonance line width measurements of a characteristic myoglobin resonance observed in bovine heart muscle spectra. The protein diffuses intracellularly at nearly half the rate observed in dilute solution. This high mobility allows the oxygenated form of myoglobin to contribute significantly to the overall diffusive flux of oxygen in respiring heart muscle.

Animals↗
PubMed1983

The primary structure of myoglobin from pacific green sea turtle (Chelonia mydas caranigra).

The amino acid sequence of the main component myoglobin from skeletal muscle of Pacific green sea turtle (Chelonia mydas caranigra) has been determined. The globin is 153 residues in length and has a free amino-terminus. The heme-binding and internal residues are as found in mammalian myoglobins. Ten substitutions are observed between this myoglobin and that from map turtle. About 38, 52, 47 and 86 substitutions are noted in comparison with the myoglobins of other reptiles, mammals, birds and fish, respectively. The inferred pattern of structural stabilization and conservation of two loci are typical of tetrapod myoglobin.

Alligators and Crocodiles↗
PubMed1983

Interactions of heme proteins with hydrogen peroxide: protein crosslinking and covalent binding of benzo[a]pyrene and 17 beta-estradiol.

This work reveals two biochemical effects of hydrogen peroxide treatment on hemoglobin, myoglobin, and cytochrome c. First, these heme proteins rapidly formed covalently crosslinked dimers and polymers detectable by detergent gel electrophoresis. Second, when treated in the presence of radioactive benzo[a]pyrene or 17 beta-estradiol, the heme proteins became covalently labeled. Nonheme proteins exhibited both cross-linking and radioactive labeling upon peroxide treatment in the presence but not the absence of heme protein or free hemin. Benzoyl peroxide or glucose and glucose oxidase effectively replaced direct addition of hydrogen peroxide. These results indicate that adventitious peroxidase activity expressed by oxygen carrying and electron transport proteins yields active oxygen species that can damage these heme proteins and nearby macromolecules, a possible biochemical mechanism for the lethal and other deleterious intracellular effects of peroxide.

Animals↗
PubMed1983

Isolation and characterisation of myoglobin from the fresh water tortoise, Trionyx niloticus.

Myoglobin was isolated from the skeletal muscle of the water tortoise, Trionyx niloticus. The myoglobin is monomeric with an apparent molecular weight of 18,000 daltons as determined on Sephadex G-75 (with a non-denaturing eluant) and 18,547 from the amino acid composition. Spectrophotometric characteristics for a variety of ferrous and ferric derivatives have been determined.

Amino Acids↗
PubMed1980

The primary structure of myoglobin from yellowfin tuna (Thunnus albacares).

The amino acid sequence of myoglobin from yellowfin tuna (Thunnus albacares) has been determined. The globin is an aminoacetylated chain containing 146 residues and having deletions, with respect to mammalian and avian myoglobins, at the NH2 terminus and two internal locations. From 79 to 85 amino acid substitutions are observed between this myoglobin and those of mammals, birds, and shark. Two external regions containing 6 and 7 residues, which are highly conserved in mammalian and avian myoglobins, are greatly or totally altered in the tuna sequence. Significant differences are apparent in the extent of electrostatic bonding in the myoglobins of fish and in those of mammals or birds.

Amino Acid Sequence↗
PubMed1979

Sequences of the soluble tryptic peptides from myoglobin of yellowfin tuna (Thunnus albacares).

1. Amino acid sequences of the soluble tryptic peptides of yellowfin tuna myoglobin, comprising 60% of the total residues, are presented. 2. The amino terminus is acetylated as shown by Fourier transform nuclear magnetic resonance spectroscopy of an N-terminal dipeptide. 3. Comparison of peptide sequences from yellowfin tuna myoglobin with corresponding regions of mammalian myoglobins shows obvious homology around the heme-attachment site and the carboxyl terminus, but marked dissimilarity is evident at other locations, such as the amino terminal region.

Acetylation↗
PubMed1977

Stabilization of bovine trypsin by reductive methylation.

Reductive methylation has little or no detectable effect on the catalytic or physicochemical properties of bovine trypsin but reduces its susceptibility to autolysis. Increased stability after methylation appears to result from the conversion of trypsin-susceptible lysine residues to trypsin-resistant epsilon-N,N-dimethyllysine residues. Reductively methylated trypsin is easily prepared and may be useful in place of trypsin where autolysis is otherwise difficult to control.

Animals↗