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G Burton

Publications and source records attributed to G Burton.

At least 91 records · Page 5Linked to original sources
PubMed1987

Versatile steroid molecules at the end of the aldosterone pathway.

18-hydroxycorticosterone converts spontaneously and reversibly to a variety of less polar forms and derivatives, some of which are precursors to aldosterone. In particular, 21-hydroxy-11 beta, 18-oxido-4-pregnene-3,20-dione (18-DAL) is hydroxylated to aldosterone with high yields in the presence of malate and NADP+, at pH 4.8. 18-DAL also behaves as a metabolic intermediate between 18-OH-B and aldosterone according to time-course and trapping experiments. Consequently, the final steps of the aldosterone pathway at pH 4.8 could be identified as 18-OH-B, 18-DAL and aldosterone, in this sequence. The submitochondrial distribution of aldosterone biosynthesis is compatible with this postulate. The work also shows that some forms of 18-OH-B are promoters of hydrogen transport in renal tubuli and that this regulation may be independent of sodium reabsorption. These results suggest a regulatory model, new in steroid biology, according to which steroid molecules bearing an oxidized angular C18-methyl may undergo structural changes between precursor ("P") and hormonal ("H") forms in response to homeostatic requirements.

18-Hydroxycorticosterone↗
PubMed1986

Biosynthesis of porphyrins and corrins. 2. Isolation, purification, and NMR investigations of the porphobilinogen-deaminase covalent complex.

The procedures for the generation of enzyme-substrate complexes from labeled porphobilinogens [(2,11-13C]PBG and [2,6,11-3H]PBG) with deaminase and the methods employed for their purification are described. Use of 13C NMR failed to detect the substrate bound to the enzyme, suggesting that the line width must be inordinately large. The complex was found to disproportionate with time when stored at 25 degrees C. However, enzyme-bound uroporphyrinogen I (uro'gen I) was detected, both in the intact protein and in the oligopeptides from tryptic digestion and peptide mapping. The first detection of an enzyme-substrate complex by 3H NMR is described for [3H]PBG and deaminase. The line widths of the observed resonances were found to be extremely large and dependent upon temperature, giving chemical shifts that suggest the involvement of a sulfhydryl group as the nucleophilic enzyme group that binds the substrate. The catalytic competence of this complex was also demonstrated by displacing bound [3H]PBG with unlabeled PBG. During the resultant formation of [3H]uro'gen I, a transient low-intensity signal was detected that has been tentatively assigned to the highly reactive azafulvene species, proposed in several mechanistic schemes for porphyrin biosynthesis.

Ammonia-Lyases↗
PubMed1986

Studies on 6 alpha-substituted penicillins. II. Synthesis and structure-activity relationships of 6 beta-(2-aryl-2-sulfoacetamido)-6 alpha-methoxy penicillanic acids.

The synthesis and antibacterial activity of 6 alpha-methoxysulbenicillin analogues (2) are described. Structure-activity studies of these derivatives bearing hydrophilic substituents in the phenyl ring led to the identification of disodium 6 beta-[D-2-(3,4-dihydroxyphenyl)-2-sulfoacetamido]-6 alpha-methoxypenicillanate (2m) as a compound with potent activity against Pseudomonas aeruginosa including beta-lactamase producing strains. Additional substitution of 2m gave derivatives 2p, 2q, 2r, with a further improvement in activity against Gram-negative bacteria.

Chemical Phenomena↗
PubMed1986

Mechanism of the inhibitory effect of 11 beta-hydroxypregna-1, 4-diene-3, 20-dione (delta HOP) at high concentrations in RNA synthesis.

The strong inhibition of thymocyte-RNA synthesis by 11 beta-hydroxypregna-1, 4-diene-3, 20-dione (delta HOP) reported recently, fulfills the three conditions required for a non-genomic effect, i.e.: no persistence upon washing out, instantaneous action and effect in the presence of inhibitors of RNA synthesis. Injection of (delta HOP) into mice (2 mg/100 g) also causes a 32% inhibition in their thymocyte-RNA synthesis, but the mechanism of this latter inhibition has still not been clarified.

Animals↗
PubMed1985

Electron impact induced fragmentations of the 1,4-diene analogues of steroid hormones and related steroids.

The electron impact induced fragmentations observed in the mass spectra of eight 1,4-diene-3-ketopregnane steroids are described. The effect of hydroxyl substituents in positions 11 beta, 17 alpha and 21, on the typical fragmentation pattern is analysed; in particular the 'long range' effect of the 17 alpha-hydroxy group on the relative abundance of the ions m/z 121 and 122 is confirmed using specific deuterium labelling.

Deuterium↗
PubMed1985

Eighteen-deoxyaldosterone and other less polar forms of 18-hydroxycorticosterone as aldosterone precursors in rat adrenals.

Samples containing as precursors either 18-hydroxycorticosterone (18-OH-B) in its M form, or this converted to less polar forms at pH 2 (ACM), or M or ACM enclosed in liposomes from adrenal lipids were incubated at pH 7.4, 4.8 or 3.3 in the presence or absence of quartered rat adrenals for 1 and 2 h. Optimal (10%) yields of aldosterone were obtained when (a) ACM was incubated at pH 4.8 and (b) M enclosed in liposomes was suspended in buffer and shaken without enzyme at pH 3.3. When conditions (a) were supplemented with malate and NADP, 16% of ACM was converted to aldosterone. ACM contained 80% of a fraction which, according to 13C NMR spectroscopy, was identical to 18-deoxyaldosterone (18-DAL). Experiments in which radioactivity from corticosterone (B) or M was trapped by radioinert M or 18-DAL disclosed a pathway comprising sequentially B, 18-OH-B, 18-DAL and aldosterone, and the combined evidence of this work, an enzymatic hydroxylation of 18-DAL to aldosterone.

18-Hydroxycorticosterone↗
PubMed1985

Preparation and structure-activity relationships of some 6 alpha-substituted penicillins.

The influence on the antibacterial activity of introducing a 6 alpha-methoxy group into carbenicillin, and various 6 alpha-substituents into sulbenicillin and piperacillin was examined. Further variations of the side chain aryl group were examined in the 6 alpha-methoxy substituted series. This led to the identification of disodium 6 beta-(D,L-2-carboxy-2-thien-3-ylacetamido)-6 alpha-methoxypenicillanate (5b) as a beta-lactamase stable derivative with useful activity against Enterobacteriaceae, and disodium 6 beta-[D-2-(4-aminophenyl)-2-sulfoacetamido]-6 alpha-methoxypenicillanate (6e) with slightly lower activity against the Enterobacteriaceae but more active against Pseudomonas aeruginosa.

Enterobacteriaceae↗
PubMed1984

13C NMR studies of glycolysis in intra- and extra-erythrocytic Babesia microti.

Metabolism in the erythrocytes of normal mice and mice infected with Babesia microti has been monitored non-invasively by high resolution 13C NMR spectroscopy. The conversion of [U-13C]glucose to lactate in both normal and infected cells together with the effect of the trypanocidal drug, 4,4'-diamidinodiazoaminobenzene diaceturate, on glycolytic rates were monitored. These studies show that erythrocytes utilize [U-13C]glucose at a rate of 3 X 10(-12) mumol cell-1 min-1 at 35 degrees C while parasitized cells consume 2.9 X 10(-11) mumol cell-1 min-1 and produce lactate as the sole end-product. This rate decreases to 9 X 10(-12) mumol cell-1 min-1 on the addition of 0.75 mM drug.

Animals↗
PubMed1984

In vitro inhibitory effects of an iodinated derivative of arachidonic acid on calf thyroid.

Thyroid glands from different species are capable of iodinating lipids including iodinate derivates of arachidonic acid. The synthesis of an iodoarachidonate derivative (IA) allowed us to explore its possible role in thyroid function; when calf thyroid slices were incubated with IA, an inhibition of 125I uptake (T/M) was observed, with concentrations as low as 10(-8)M. The decrease of the T/M values reached a plateau at 10(-4)M. Arachidonic acid (AA) also decreased 125I uptake. Besides, IA caused a significant inhibition of 125I organification both in thyroid slices and homogenates. AA was without effect on this parameter. The stimulatory effect of TSH on 125I organification was also significantly impaired by IA at 10(-5)M. IA produced a significant decrease in 3H-uridine incorporation into total RNA. This effect is due to a diminution of 3H-uridine uptake as well as to a probable action at a transcriptional step. The addition of MMI did not alter the inhibitory action of IA, and AA was without effect. Therefore we may conclude that IA has an inhibitory action on the thyroid per se at the membrane level and in different subcellular sites. These results suggest a possible role of IA in thyroid autoregulation.

Animals↗
PubMed1983

Dissociation of glucocorticoid effects of C-21 steroids at high concentrations in thymocytes.

A dissociation between inhibition of RNA synthesis and cell lysis was observed when thymocytes of adrenalectomized rats were incubated with high concentrations of pregn-4-ene-11 beta-ol-3,20-dione and pregna-1,4-diene-11 beta-ol-3,20-dione. In contrast, no dissociation of these effects was found with the typical glucocorticoids cortisol and corticosterone, nor with their 1,4-diene analogs under the same conditions.

Animals↗
PubMed1981

Control of porphyrin biosynthesis in Rhodopseudomonas spheroides and Propionibacterium shermanii. A direct 13C nuclear-magnetic-resonance spectroscopy study.

The facultative anaerobes Rhodopseudomonas spheroides and Propionibacterium shermanii were grown under anaerobic and aerobic conditions. The effect of light was studied with the photosynthetic R. spheroides, and the adaptation of both species to dark anaerobic life was monitored by direct observation of 5-amino[5-13C]laevulinic acid metabolism by using 13C nuclear-magnetic-resonance spectroscopy.

Aerobiosis↗