THE METABOLISM OF L-SERYLGLYCINE O(35S)-SULPHATE IN THE RAT.
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ABSTRACT:
SUBMITTER: TUDBALL N
PROVIDER: S-EPMC1206793 | biostudies-other | 1965 Jun
REPOSITORIES: biostudies-other
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Project description:The metabolic fate of heparan N-[(35)S]sulphate was studied in rats. Heparan sulphate was obtained from either bovine aorta or lung and labelled with (35)S by desulphation and subsequent resulphation in vitro. Experiments in which heparan N-[(35)S]sulphate was administered intravenously to either free-range or wholly anaesthetized rats with ureter cannulae established that substantial desulphation occurs in vivo, with elimination of inorganic [(35)S]sulphate in urine. Oligosaccharides labelled with (35)S, possible intermediates in heparan sulphate degradation, could not be detected in urine or blood. The general distribution of radioactivity after administration of heparan N-[(35)S]sulphate, as demonstrated by whole-body radioautography, suggested that desulphation was not restricted to one organ in particular. Support for this view was obtained in experiments in which heparan N-[(35)S]sulphate was administered to animals after the removal of kidneys, liver, spleen, pancreas or gastrointestinal tract. In all cases inorganic [(35)S]sulphate was still produced. The ability of rats of desulphate heparan N-[(35)S]sulphate was progressively impaired by increasing concentrations of heparin administered simultaneously. It was concluded that heparan sulphate is metabolized at a number of sites in the body by a sequence of degradative events leading to the formation of inorganic sulphate. It is also concluded that at least some of these events are common to heparan sulphate and heparin.
| S-EPMC1165019 | biostudies-other
Project description:1. When Na235SO4 is injected intravenously in rats, it is immediately available for sulphate conjugation of the phenolic drug harmol (7-hydroxyl-1-methyl-9H-pyrido[3,4-b]indole) in the liver. This was established by following the time course of the biliary excretion of the sulphate conjugate of harmol, and the incorporation of [35S]sulphate into harmol sulphate. 2. During the 10min immediately after injection of Na235SO4 re-distribution of [35S]sulphate took place, which resulted in a rapid initial decrease in the plasma concentration of [35S]sulphate; a concomitant decrease in the amount of [35S]sulphate incorporated into harmol sulphate was observed, indicating that the co-substrate of sulphation, adenosine 3'-phosphate 5'-sulphatophosphate, equilibrates rapidly with [35S]sulphate in plasma. 3. The results suggest that the pool size of adenosine 3'-phosphate 5'-sulphatophosphate is very small; therefore the specific radioactivity of [35S]sulphate in plasma determines the specific radioactivity incorporated into sulphate esters at any time.
| S-EPMC1185690 | biostudies-other
Project description:Rat liver cells grown in primary cultures in the presence of [(35)S]sulphate synthesize a labelled heparan sulphate-like glycosaminoglycan. The characterization of the polysaccharide as heparan sulphate is based on its resistance to digestion with chondroitinase ABC or hyaluronidase and its susceptibility to HNO(2) treatment. The sulphate groups (including sulphamino and ester sulphate groups) are distributed along the polymer in the characteristic block fashion. In (3)H-labelled heparan sulphate, isolated after incubation of the cells with [(3)H]galactose, 40% of the radioactive uronic acid units are l-iduronic acid, the remainder being d-glucuronic acid. The location of heparan sulphate at the rat liver cell surface is demonstrated; part of the labelled polysaccharide can be removed from the cells by mild treatment with trypsin or heparitinase. Further, a purified plasma-membrane fraction isolated from rats previously injected with [(35)S]sulphate contains radioactively labelled heparan sulphate. A proteoglycan macromolecule composed of heparan sulphate chains attached to a protein core can be solubilized from the membrane fraction by extraction with 6m-guanidinium chloride. The proteoglycan structure is degraded by treatment with papain, Pronase or alkali. The production of heparan [(35)S]sulphate by rat liver cells incubated in the presence of [(35)S]sulphate was followed. Initially the amount of labelled polysaccharide increased with increasing incubation time. However, after 10h of incubation a steady state was reached where biosynthetic and degradative processes were in balance.
| S-EPMC1164759 | biostudies-other
Project description:To investigate the metabolism of proteoglycans in young growing rats, calvaria, incisors, femoral diaphysis and metaphysis were labelled in vivo for 0.5-72 h with [35S]sulphate. At each time point the specific radioactivity, expressed as c.p.m. of [35S]sulphate/micrograms of uronic acid, of papain-resistant macromolecules in each tissue was determined. The identity of the glycosaminoglycans was established by the use of specific enzymic and chemical methods of degradation. Incorporation of the label into each tissue was maximal at 12 h; it then declined to 50-75% of that value by 72 h. Chondroitin sulphate was the predominant glycosaminoglycan in each tissue, representing 80-96% of the total; heparan sulphate comprised 2-14% of the total; in general, radioactive material sensitive to keratanase comprised less than 1% of the total. The relative amount of labelled chondroitin sulphate increased, whereas that of heparan sulphate decreased, with increasing time of incorporation. These data show that 25-50% of the newly synthesized glycosaminoglycans are lost from mineralizing tissues, during the time in which the newly secreted organic matrix becomes mineralized.
| S-EPMC1144531 | biostudies-other
Project description:The metabolic fate and mode of excretion of cyclohexylphenyl 4-[35S]sulphate were studied in the guinea pig. Up to 54.8% of the dose appeared in the bile, the majority as unchanged ester. Substantial amounts of hydroxylated cyclohexylphenyl 4-[35S]sulphate were also excreted in the bile together with minor amounts of the corresponding glucuronic acid conjugate. When isolated guinea-pig livers were perfused with cyclohexylphenyl 4-[35S]sulphate the biliary components were the same as those in the intact animal, although the relative concentration of the hydroxylated derivative was significantly greater. When the hydroxylated derivative was re-injected into guinea pigs it was excreted almost entirely unchanged in the bile. However, in the rat, it was excreted in the bile as a glucuronic acid conjugate. These findings are discussed in relation to studies carried out in the rat [Hearse, Powell, Olavesen & Dodgson (1969) Biochem. Pharmacol. 18, 181--195] and to differences in enzyme activities in rat and guinea-pig liver. The results are also discussed in terms of the molecular-weight threshold for the excretion of anions in guinea-pig bile.
| S-EPMC1186252 | biostudies-other
Project description:The metabolic fates of the synthetic surfactants, sodium [1-(14)C]undecyltriethoxy sulphate and sodium [1-(14)C]dodecyltriethoxy sulphate were studied in the rat. Both compounds were extensively metabolized regardless of the route of administration, oral, intraperitoneal or intravenous. Short-chain radioactive products were eliminated in the urine: the major metabolite of the dodecyl homologue in the urine was identified as (-)O(2)C(14)CH(2)- (OC(2)H(4))(3)OSO(3) (-) by n.m.r. and g.l.c.-mass spectrometry, whereas the major metabolite of the undecyl homologue in the urine was tentatively identified as (-)O(2)CCH(2) (14)CH(2)- (OC(2)H(4))(3)OSO(3) (-). In contrast with experiments with the dodecyl derivative, when [1-(14)C]undecyltriethoxy sulphate was administered to rats, appreciable amounts of radioactivity were recovered as (14)CO(2) in expired air. Whole-body radioautography implicated the liver as the major site of metabolism of both surfactants. The nature of the metabolic products establishes that both compounds are degraded by omega,beta-oxidation. Cleavage of the ether linkage proximal to the sulphate moiety may account for the small amounts of (14)CO(2) recovered in expired air after the administration of [1-(14)C]dodecyltriethoxy sulphate. It is suggested the substantial amounts of (14)CO(2) recovered after [1-(14)C]-undecyltriethoxy sulphate administration originate from (-)O(2) (14)C(OC(2)H(4))(3) OSO(3) (-), an unstable product of omega,beta-oxidation. An n.m.r. spectrum of the metabolite identified as 2-(triethoxy sulphate)acetic acid and a mass spectrum of the trimethylsilyl derivative of the parent alcohol of that metabolite have been deposited as Supplementary Publication SUP50086 (5 pages) at the British Library Lending Division, Boston Spa, Wetherby, West Yorkshire LS23 7BQ, U.K., from whom copies can be obtained on the terms indicated in Biochem. J. (1978) 169, 5.
| S-EPMC1185928 | biostudies-other
Project description:1. The incorporation of [(35)S]sulphate in vivo into the acid-soluble intermediates extracted from young rat skin showed three sulphated hexosamine-containing components. 2. The rates of synthesis of these components were determined in vivo by measuring the incorporation of radioactivity from [U-(14)C]glucose into their isolated hexosamine moieties. 3. The incorporation of radioactivity from [U-(14)C]glucose into the isolated hexosamine and uronic acid moieties of the acid glycosaminoglycans was also measured. These results, combined with those obtained on the intermediary pathways of hexosamine and uronic acid biosynthesis previously determined in this tissue, indicated that the acid-soluble sulphated hexosamine-containing components were not precursors of the sulphated hexosamine found in the acid glycosaminoglycans. 4. The rates of synthesis of the acid glycosaminoglycan fractions were calculated from the incorporation of radioactivity from [U-(14)C]glucose into the hexosamine moiety. The sulphated components containing principally dermatan sulphate, chondroitin 6-sulphate and in smaller amounts, chondroitin 4-sulphate, heparan sulphate and heparin appeared to be turning over about twice as rapidly as hyaluronic acid and about four times as rapidly as the small keratan sulphate fraction. The relative rates of synthesis of the sulphated glycosaminoglycans were calculated from the incorporation of [(35)S]sulphate and were in agreement with those from (14)C-labelling studies.
| S-EPMC1179489 | biostudies-other
Project description:Sulphate-reducing bacteria (SRB) are studied across a range of scientific fields due to their characteristic ability to metabolise sulphate and produce hydrogen sulphide, which can lead to significant consequences for human activities. Importantly, they are members of the human gastrointestinal microbial population, contributing to the metabolism of dietary and host secreted molecules found in this environment. The role of the microbiota in host digestion is well studied, but the full role of SRB in this process has not been established. Moreover, from a human health perspective, SRB have been implicated in a number of functional gastrointestinal disorders such as Irritable Bowel Syndrome and the development of colorectal cancer. To assist with the study of SRB, we present a mathematical model for the growth and metabolism of the well-studied SRB, Desulfovibrio vulgaris in a closed system. Previous attempts to model SRB have resulted in complex or highly specific models that are not easily adapted to the study of SRB in different environments, such as the gastrointestinal tract. We propose a simpler, Monod-based model that allows for easy alteration of both key parameter values and the governing equations to enable model adaptation. To prevent any incorrect assumptions about the nature of SRB metabolic pathways, we structure the model to consider only the concentrations of initial and final metabolites in a pathway, which circumvents the current uncertainty around hydrogen cycling by SRB. We parameterise our model using experiments with varied initial substrate conditions, obtaining parameter values that compare well with experimental estimates in the literature. We then validate our model against four independent experiments involving D. vulgaris with further variations to substrate availability. Further use of the model will be possible in a number of settings, notably as part of larger models studying the metabolic interactions between SRB and other hydrogenotrophic microbes in the human gastrointestinal tract and how this relates to functional disorders.
| S-EPMC6653664 | biostudies-literature
Project description:Intraperitoneal, intravenous or oral administration of sodium oestrone [(35)S]-sulphate to male and female Medical Research Council hooded rats is followed by the rapid excretion of the bulk of the radioactivity in urine in the form of inorganic [(35)S]sulphate. Pre-treatment of rats with an antibiotic regimen does not affect the results except in the case of oral administration, when relatively large amounts of the dose are recovered as ester [(35)S]sulphate in faeces. Intravenous administration of the labelled ester to male and female rats with cannulae in bile duct and ureter gave results similar to those obtained with free-range animals. Only small amounts of radioactivity appeared in bile and this was mainly in the form of ester sulphate, including both oestrone [(35)S]sulphate and oestradiol-17beta 3[(35)S]-sulphate. Whole-body radioautography pinpointed the liver as the probable site of the desulphation of the sulphate ester and this was confirmed by liver and kidney perfusion experiments and by studies with rats in which kidney function had been eliminated by ligation of the renal pedicles.
| S-EPMC1176931 | biostudies-other
Project description:The metabolic fate of potassium dodecyl [(35)S]sulphate was studied in rats. Intraperitoneal and oral administration of the ester into free-ranging animals were followed by the excretion of the bulk of the radioactivity in the urine within 12hr., approximately 17% being eliminated as inorganic [(35)S]sulphate. Similar results were obtained in experiments in which potassium dodecyl [(35)S]sulphate was injected intravenously into anaesthetized rats with bile-duct and ureter cannulae. Analysis of urinary radioactivity revealed the presence of a new ester sulphate (metabolite A). This metabolite was isolated, purified and subsequently identified as the sulphate ester of 4-hydroxybutyric acid by paper, thin-layer and gas chromatography, by paper electrophoresis and by comparison of its properties with those of authentic butyric acid 4-sulphate. The identity of the metabolite was confirmed by isotope-dilution experiments. When either purified metabolite A or authentic potassium butyric acid 4[(35)S]-sulphate was administered to free-ranging rats the bulk of the radioactivity was eliminated unchanged in the urine within 12hr., approx. 20% of the dose appearing as inorganic [(35)S]sulphate. Whole-body radioautography and isolated-liver-perfusion experiments implicated the liver as the major site of metabolism of potassium dodecyl [(35)S]sulphate. It is suggested that butyric acid 4-sulphate probably arises by omega-oxidation of dodecyl sulphate to a fatty acid-like compound, which is then degraded by beta-oxidation.
| S-EPMC1187492 | biostudies-other