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Biomedical subjects

S B Brown

Publications and source records attributed to S B Brown.

At least 127 records · Page 7Linked to original sources
PubMed1979

The dimerization of ferrihaems. IV. Studies on haematoferrihaem and a general appraisal of the nature and implications of dimerization.

The dimerization of haematoferrihaem was studied in phosphate buffer in the pH range 7.02--8.14. The absorbance of dilute solutions decreased over a period of several hours due to adsorption of haematoferrihaem to glass vessels. This problem was overcome by using dilute solutions within 10 min of preparation. Spectrophotometric data were consistent with a dimerization process according to the equation 2 monomer in equilibrium dimer + H+ as found earlier for other ferrihaems studied. The value of K, defined as K = [dimer] [H+]/[monomer]2, was found to be 1.00 . 10(-2). Rate constants for the forward and reverse steps in dimerization were determined at pH values of 6.63, 7.01 and 7.44, using the temperature-jump technique. The reaction pathway for dimerization was found to be similar to those of deuteroferrihaem and mesoferrihaem, but different from that of coproferrihaem. A general appraisal of the factors influencing dimerization is attempted in the light of accumulated data on various ferrihaems. With the exception of protoferrihaem, it is suggested that dimerzation increases with the hydrophobicity of the 2,4 substituents. The additional stability of the protoferrihaem dimer is explained in terms of increased interaction due to conjugation of the vinyl groups with the porphyrin macrocycle.

Adsorption↗
PubMed1979

Fertility in psychiatric outpatients.

The fertility rates of 223 female schizophrenic outpatients and 479 female nonschizophrenic outpatients were compared to a probability sample of 300 women residing in the same geographic area, metropolitan Atlanta, and from the same social strata as the patients. Age- and race-adjusted comparisons showed that the mean number of children per woman and levels of unwanted and unplanned fertility did not differ in the different diagnostic groups. Furthermore, the rates were not lower for the psychiatric patients than for the general population. In order to reduce an important source of psychiatric morbidity, those in the mental health professions need to pay more attention to the family planning desires of their patients.

Adult↗
PubMed1978

The dimerization of ferrihaems. III. Equilibrium and kinetic studies on the dimerization of coproferrihaem.

Spectrophotometric studies on the behaviour of coproferrihaem in aqueous solution showed that, in the pH range 6.66--8.04, a dimerization process occurs according to the equation 2 monomer K in equilibrium dimer + H+ The value of K, the pH-independent dimerization constant, was found to be 2.10 . 10(-3), signifying that coproferrihaem shows the least tendency to dimerize of any ferrihaem so far investigated. Forward and reverse rate constants for the dimerization process have been determined by the temperature-jump method. The results suggest that the cation-bridging between carboxyl residues, postulated for the dimers of the dicarboxylic ferrihaems, cannot occur between the additional carboxyl residues of coproferrihaem and that the increased negative charge may cause destabiliztion of the coproferrihaem dimer by repulsion effects.

Chemical Phenomena↗
PubMed1978

Catalase model systems. Decomposition of hydrogen peroxide catalysed by mesoferrihaem, deuteroferrihaem, coproferrihaem and haematoferrihaem.

The catalytic decomposition of H2O2 by deuteroferrihaem, mesoferrihaem, coproferrihaem and haematoferrihaem was studied as a model for the mechanism of action of catalase. For haematoferrihaem, anomalous but reproducible results were obtained, which could not be adequately explained. For each of the other ferrihaems studied, both monomeric and dimeric species catalysed decomposition, although the activity of monomer (aM) was much greater than that of dimer (aD). The pH variation of aD in the range 6.5--11 was consistent with an inverse dependence on [H+]1/2. The molecular mechanism whereby such a dependence could be achieved is not apparent. A study of the pH-dependence of aM in the range 6.5--11 revealed a linear inverse relationship with [H+]. This is interpreted in terms of attack by HO2- on ferrihaem monomer. The specific pH-independent rate constants for this reaction were in the order coproferrihaem greater than protoferrihaem greater than or equal to mesoferrihaem congruent to deuteroferrihaem. The order of magnitude of these rate constants is the same as that for catalysis by Fe(H2O)63+ and the second-order rate constant for decomposition of H2O2 by catalase. The implications on the mechanism of action of catalase are discussed.

Catalase↗
PubMed1978

The role of peroxide in haem degradation. A study of the oxidation of ferrihaems by hydrogen peroxide.

The oxidation of ferrihaems by H2O2 was studied as a model for haem catabolism. Rates of ferrihaem oxidation were evaluated by using a new computer-based method that measures the loss in catalytic activity of the ferrihaem during oxidation. For protoferrihaem, deuteroferrihaem, coproferrihaem and mesoferrihaem, oxidation proceeded via the monomeric species and no dimer contribution was detectable. The pH-dependence of oxidation was studied in the range 6.5--11. Within experimental error, the data were compatible with an inverse linear dependence on [H+]. This was interpreted in terms of attack by HO2- on monomeric ferrihaem. The specific second-order rate constants for oxidation of monomeric species by HO2- were of the same order of magnitude for all the ferrihaems, and were in the sequence coproferrihaem greater than protoferrihaem greater than mesoferrihaem congruent to deuteroferrihaem. A model is suggested involving formation of a ferrihaem monomerperoxide complex, which may either dissociate with the formation of a peroxidatic intermediate or be involved in an intramolecular oxidation of the ferrihaem. Haem catabolism may occur via the same or a similar intermediate.

Coproporphyrins↗
PubMed1978

Haem degradation in abnormal haemoglobins.

The coupled oxidation of certain abnormal haemoglobins leads to different bile-pigment isomer distributions from that of normal haemoglobin. The isomer pattern may be correlated with the structure of the abnormal haemoglobin in the neighbourhood of the haem pocket. This is support for haem degradation by an intramolecular reaction.

Bile Pigments↗
PubMed1978

The mechanism of haem catabolism. A study of haem breakdown in spleen microsomal fraction and in a model system by 18O labelling and metal substitution.

The mechanism of bile-pigment formation from haem breakdown was studied by using 18O labelling of the molecular oxygen required for macrocyclic ring cleavage. For haem degradation by the spleen microsomal haem oxygenase system, mass spectrometry of the product bilirubin revealed that cleavage occurred by the Two-Molecule Mechanism, i.e. the terminal lactam oxygen atoms in bilirubin were derived from two different oxygen molecules. Similarly, degradation of myoglobin by coupled oxidation with ascorbate and oxygen proceeded via the Two-Molecule Mechanism. Cobalt and manganese complexes of protoporphyrin IX were not degraded by either the haem oxygenase system or the coupled oxidation system. This result suggests that the iron atom possesses unique properties in facilitating porphyrin breakdown.

Animals↗
PubMed1978

Phycocyanobilin synthesis in the unicellular rhodophyte Cyanidium caldarium.

Light is required for synthesis of the accessory photosynethetic pigment phycocyanin in cells of the unicellular rhodophyte Cyanidium caldarium. Phycocyanin is a conjugated protein composed of polypeptide subunits to which the light-absorbing bile pigment chromophore phycocyanobilin is covalently attached. Dark-grown cells of C. caldarium are unable to make phycocyanin, but when incubated in the dark with 5-aminolaevulinate the cells synthesize and excrete a protein-free phycobilin (algal bile pigment) into the suspending medium. The electronic absorption spectrum, electron impact mass spectrum, chromatographic properties and imide products obtained after chronic acid degradation of the excreted phycobilin were identical with those of phycocyanobilin cleaved from phycocyanin in boiling methanol. This establishes the structural identity between the excreted phycobilin, which is the end product of bile-pigment synthesis in vivo, and the chromophore cleaved from phycocyanin in boiling methanol. The significance of the structure of the excreted phycobilin with respect to the events surrounding the assembly of the phycocyanin molecule in vivo is discussed.

Bile Pigments↗
PubMed1978

The dimerization of ferrihaems. I. The effect of buffer ions and specific cations on deuteroferrihaem dimerization.

The dimerization of dueteroferrihaem in aqueous solution has been investigated using a parameter, named the dimerization index (Robs). This is defined as the ratio of extinction coefficients at wavelengths corresponding to Soret band maxima for the monomeric and dimeric species, respectively. For solutions containing mainly monomeric species, Robs greater than 2, whereas for solutions containing mainly dimeric species Robs less than 1. A computer programme has been applied to determine values of the dimerization constant, K, defined as: K = [dimer] [H+]/[monomer]2. Phosphate buffer anions and Tris . HCl buffer enhanced dimerization. Monovalent and divalent cations also increased dimerization, but in a specific manner. The magnitudes of their effects increased in the order K+ less than Na+ less than Li+ less than Sr2+ less than Mg2+ approximately or equal to Ca2+. Values of K were determined for several concentrations of Na+ and Sr2+. These data are interpreted in terms of a stabilization of the ferrihaem dimer by the formation of ion triplets with the added cation 'sandwiched' between carboxyl residues of the adjacent ferrihaem monomeric units. General guidelines are recommended for the choice of conditions which minimize dimerization.

Buffers↗
PubMed1978

The dimerization of ferrihaems. II. Equilibrium and kinetic studies of mesoferrihaem dimerization.

Spectrophotometric data have been determined for mesoferrihaem at several pH values and over a range of concentration covering four orders of magnitude. The data reveal a dimerization process according to the equation 2 monomer in equilibrium dimer + H+, analogous to earlier findings for deuteroferrihaem and protoferrihaem. The value of K (defined as K = [dimer] [H+]/[monomer]2) was found to be 6.92.10(-2). This is close to the value for deuteroferrihaem but much less than that for protoferrihaem. This is interpreted in terms of possible additional bonding between the delocalized electron systems in protoferrihaem dimers relative to those of mesoferrihaem and deuteroferrihaem. Rate constants for dimerization were determined by temperature-jump spectrophotometry. The pH dependence of the rate constants is explained in terms of two distinct pathways for the dimerization process. These involve either direct reaction between two undissociated monomer molecules or alternatively an initial acid dissociation of a monomer molecule followed by reaction between an undissociated and dissociated molecule.

Chemical Phenomena↗
PubMed1978

The mechanism of haem catabolism. Bilirubin formation in living rats by [18O]oxygen labelling.

1. The pathway of haem breakdown in living rats was studied by using 18O in the oxygen that the animals consumed. By cannulation of the common bile duct and collection of bile, labelled bilirubin was isolated and its mass spectrum determined. One set of results was obtained for a rat to which haemoglobin had been intravenously administered and another set obtained for a rat that was not given exogenous haem. Isomerization of bilirubin IXalpha to the XIIIalpha and IIIalpha isomers did not occur to any significant extent. The 18O-labelling pattern obtained in the bilirubin was consistent with a Two-Molecule Mechanism, whereby the terminal lactam oxygen atoms of bilirubin are derived from different oxygen molecules. The consequences of this mechanism are discussed in terms of the possible intermediates of the catabolic pathway. 2. 18O-labelled bilirubin appeared in the bile in less than 10 min after exposure of the animals to labelled oxygen. This result suggests that all of the chemical transformations involving production of biliverdin, reduction to bilirubin and conjugation of the bilirubin are fast processes. 3. The quantitative recovery of label obtained in the experiments suggests that there is little or no exchange of newly synthesized bilirubin with existing bilirubin pools in the animal.

Animals↗
PubMed1976

Stereospecific haem cleavage. A model for the formation of bile-pigment isomers in vivo and in vitro.

A new approach is suggested for an explanation of sterospecific haem degradation to biliverdin and bilirubin. A model is proposed in which an oxygen molecule, bound to the haem iron atom, attacks a methene-bridge carbon atom in an intramolecular reaction. Specificity of macrocyclic ring cleavage is explained on the basis of the different accessibilities of the bound oxygen molecule to the four methene bridges. The consequences of these ideas are assessed in relation to coupled oxidation in model systems and to haem catabolism.

Animals↗