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Biomedical subjects

S B Brown

Publications and source records attributed to S B Brown.

At least 109 records · Page 6Linked to original sources

Haem degradation in human haemoglobin in vitro. Separation of the contribution of the alpha- and beta-subunits.

Human haemoglobin was prepared containing [14C]haem in either the alpha- or the beta-subunits. Coupled oxidation of such hybrid haemoglobins with ascorbate and O2 showed that the biliverdin produced by the alpha-subunits contained approx. 55% alpha-isomer and 45% beta-isomer, whereas that produced by the beta-subunits contained approx. 75% alpha-isomer and 25% beta-isomer. Coupled oxidation of isolated alpha- and beta-subunits gave approx. 70% alpha-isomer, 30% beta-isomer and 78% alpha-isomer, 22% beta-isomer respectively. These results are consistent with calculations of differences in the haem environment in the two subunit types.

Biliverdine↗

Ferrochelatase activity in the photosynthetic alga Cyanidium caldarium. Development of the enzyme during biosynthesis of photosynthetic pigments.

Dark-grown cells of the photosynthetic alga Cyanidium caldarium were shown to contain ferrochelatase activity, which increased markedly when the cells were induced to form pigments by exposure to light. Km values for the crude enzyme preparation were 14.8 microM and 6.5 microM for binding of Co2+ and deuteroporphyrin IX respectively.

Ferrochelatase↗

Biosynthesis of phycobiliproteins. Incorporation of biliverdin into phycocyanin of the red alga Cyanidium caldarium.

14C-labelled biliverdin IX alpha was administered to cultures of Cyanidium caldarium that were actively synthesizing photosynthetic pigments in the light. Between 9 and 12% of the phycobiliprotein chromophore produced in such cultures was derived from exogenous biliverdin. These results demonstrate that biliverdin is an intermediate in the biosynthesis of phycobiliproteins.

Bilirubin↗

Biosynthesis of the chromophore of phycobiliproteins. A study of mesohaem and mesobiliverdin as possible intermediates and further evidence for an algal haem oxygenase.

The possible roles of mesohaem and mesobiliverdin as metabolic precursors of phycocyanobilin, the chromophore of phycocyanin, were studied in the unicellular rhodophyte Cyanidium caldarium. Dark-grown cells of this organism, which had been exposed to mesohaem, were either incubated in the dark with 5-aminolaevulinate, which results in excretion of bilins into the suspending medium, or incubated in the light, which results in synthesis of phycocyanin within the cells. By using 14C-labelling, either in the mesohaem or in the 5-aminolaevulinate administered, it was shown that mesohaem is not a precursor of phycocyanobilin in either dark or light systems. However, mesohaem was converted into mesobiliverdin in both systems, a phenomenon that is further evidence for the existence of an algal haem oxygenase. The data also showed that mesobiliverdin is not a precursor of phycocyanobilin. These results suggest that algal bilins are formed via haem degradation to biliverdin in the same way as mammalian bile pigments.

Aminolevulinic Acid↗

CT characteristics of the normal pituitary gland.

Fifty-three patients undergoing orbital computed tomographic (CT) scanning for symptoms and signs unrelated to the pituitary gland had coronal and sagittal reformations of contiguous 1.5 mm slices through the sella. Mean male gland height was 4.1 +/- 1.1 mm, mean female gland height was 4.4 +/- 1.4 mm; no statistically significant differences with age were identified. Pituitary glands were homogeneous in 58% and inhomogeneous in 42% of patients; 91.5% had flat or concave superior surfaces. Coronal and saggital CT reformations are felt to be important in the evaluation of the pituitary gland.

Adult↗

Haem disorder in reconstituted human haemoglobin.

Degradation of the haem of haemoglobin (used as a chemical probe of the haem-protein relationship), suggests that reconstituted human haemoglobin contains significant haem disorder. This results from the insertion of haem into globin with an orientation 180 degrees different from the natural orientation. Haem disorder also slowly occurs in methaemoglobin solutions.

Ascorbic Acid↗

The effect of N-methylprotoporphyrin IX on the synthesis of photosynthetic pigments in Cyanidium caldarium. Further evidence for the role of haem in the biosynthesis of plant billins.

N-Methylprotoporphyrin IX strongly inhibits synthesis of phycocyanobilin, but not chlorophyll a, in the dark. In the light, both phycocyanin and chlorophyll a synthesis are inhibited in parallel. These results are consistent with the intermediacy of haem in algal bilin synthesis and suggest a control mechanism for chlorophyll a synthesis, previously unknown.

Aminolevulinic Acid↗

A study of the mechanism of quercetin oxygenation by 18O labelling. A comparison of the mechanism with that of haem degradation.

The mechanism of quercetin oxygenation, which is formally analogous to haem degradation, was studied by using 18O labelling. In both the enzymic oxygenation (catalysed by quercetinase) and the non-enzymic reaction (base-catalysed), both oxygen atoms incorporated into product were derived from a single oxygen molecule. Quercetin oxygenation therefore occurs by a classical dioxygenase mechanism and is not an appropriate model for study of the mechanism of haem catabolism.

Dioxygenases↗

CT of irradiated solid tumor metastases to the brain.

Twenty patients with solid tumor metastases to the brain, demonstrated by CT scanning, had follow-up scans after radiation therapy of the metastatic focus. Nine patients (45%) showed no evidence of the metastasis on the initial follow-up scans. Another 10 patients (50%) showed some improvement in the size, enhancement, or surrounding edema of the lesion. Only one patient showed progression in spite of therapy. The CT scan identified those patients who achieved longer survival and/or longer time intervals before brain relapse. However, CT scans must be interpreted with caution in patients still on corticosteroid treatment. Additionally, other non-tumoral conditions may mimic tumor recurrence. Radiation therapy offered palliation in patients with brain metastases, and in some instances, sterilized patients of their metastatic brain involvement.

Adult↗

Bile pigment synthesis in plants. Incorporation of haem into phycocyanobilin and phycobiliproteins in Cyanidium caldarium.

A procedure was developed whereby haem was taken up by dark-grown cells of the unicellular rhodophyte Cyanidium caldarium. These cells were subsequently incubated either in the dark with 5-aminolaevulinate, which results in excretion of phycocyanobilin into the suspending medium or incubated in the light, which results in synthesis and accumulation of phycocyanin and chlorophyll a within the cells. Phycocyanobilin was isolated from phycocyanin by cleavage from apoprotein in methanol. Phycocyanobilin prepared from phycocyanin or excreted from cells given 5-aminolaevulinate was methylated and purified by t.l.c. By using 14C labelling either in the haem or in 5-aminolaevulinate administered, haem incorporation into phycocyanobilin was demonstrated in both dark and light systems. Since chlorophyll a synthesized in the light in the presence of labelled haem contained no radioactivity, it was clear that haem was directly incorporated into phycocyanobilin and not first converted into protoporphyrin IX. These results clearly demonstrate phycocyanobilin synthesis via haem and not via magnesium protoporphyrin IX as has also been postulated.

Aminolevulinic Acid↗

Orientation of oxygen in oxyhaemoproteins and its implications for haem catabolism.

Haem is degraded to bile pigments in the catabolism of haemoproteins in mammals and in the formation of photosynthetic pigments in algae. The first stage of this reaction involves oxygen attack at one of the four methene-bridge carbon atoms, which is ultimately eliminated as CO(ref. 1). The four bridges are not sterically equivalent (Fig. 1) and the bilirubin in mammalian bile and algal bile pigments consists almost exclusively of the alpha-isomers. Little is known about the structures of the ring-cleaving enzymes responsible, although microsomal haem oxygenase, which catalyses the breakdown of haem to biliverdin in mammals, has very similar spectroscopic properties to myoglobin. The degradation process has been simulated in vitro by a 'coupled oxidation' method in which the proportions of the four possible isomeric products depend on the nature of the globin moiety to which the haem is bound. We report here the use of an interactive computer display system to explore the relative accessibilities of the four methene bridges to a haem-bound oxygen molecule in myoglobin and in the alpha and beta chains of haemoglobin. Our calculated interaction energies agree well with the proportions of the four isomers that are observed experimentally.

Animals↗

Accumulation of chemostimulatory amino acids by a sedimentable fraction isolated from olfactory rosettes of rainbow trout (Salmo gairdneri).

The accumulation of amino acids by a sedimentable fraction from olfactory rosettes of rainbow trout (Salmo gairdneri) was examined to determine the correspondence with established criteria for receptors. Physical parameters such as saturability, reversibility, affinity and quantity of sites were reasonably consistent with receptor criteria. The kinetics of association were slow and not in accord with values expected of sensory receptors. Accumulation correlated with electrophysiological effectiveness for most amino acids. The correlation was tissue specific, not being evident in brain or gill. Denervation experiments showed that high-affinity accumulation depended upon the presence of neuronal elements in the olfactory mucosa. Inhibition studies with amino acids and analogues generally indicated good correspondence with previous electrophysiological findings. Experiments with transport inhibitors, lack of Na+, counter-transport and increasing osmotic strength showed some involvement of amino acid transport. Inconsistencies between the various aspects of amino acid accumulation by the sedimentable fraction and electrophysiological response preclude unequivocal classification of the accumulation as representing olfactory receptors.

Acetates↗

Mechanism of photooxidation of bacteriochlorophyll c derivatives. A possible model for natural chlorophyll breakdown.

The photooxidation of methyl pheophorbides, derived from bacteriochlorophyll c, yields ring-opened acetylbilitrienes which are structurally related to mammalian bile pigments. The mechanism of this photooxidation, and that of certain mesomethyl-substituted model compounds, has been studied using 18O labeling with molecular oxygen. In all cases, the methine bridge carbon atoms were retained in the ring-opened photoproducts and both oxygen atoms incorporated into the acetylbilitriene photoproducts were derived from a single oxygen molecule. In this respect, ring opening of bacteriochlorophyll c derivatives and mesomethyl-substituted model compounds differs from the nonphotochemical (enzymatic) ring opening of heme which involves elimination of the methine bridge carbon atom as carbon monoxide and insertion of two oxygen atoms, each from a different molecule of molecular oxygen. The process of photooxidation of bacteriochlorophyll c and mesomethyl-substituted model compounds studied may have implications for the mechanism of natural degradation of chlorophyll a and b during leaf senescence and grain ripening.

Bacteria↗

Mechanism of bile-pigment synthesis in algae. 18O incorporation into phycocyanobilin in the unicellular rhodophyte, Cyanidium caldarium.

The origin of the lactam oxygen atoms of phycocyanobilin from Cyanidium caldarium was studied using 18O labelling. By inhibiting photosynthesis, a high 18O enrichment was maintained in the gas phase and the resulting incorporation of label showed that the lactam oxygen atoms were derived from two oxygen molecules. Slow exchange of these oxygen atoms with water was demonstrated directly by using H218O.

Bile Pigments↗