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Biomedical subjects

G J Dutton

Publications and source records attributed to G J Dutton.

50 records · Page 3Linked to original sources
PubMed1973

Some properties of the uridine diphosphate glucuronyltransferase activity synthesizing thio-beta-D-glucuronides.

1. Some properties of the UDP-glucuronyltransferase synthesizing thio-beta-d-glucuronides were investigated and compared with those of the enzyme synthesizing the O-glucuronides of analogous phenols. 2. Enzyme activity was generally similar for both classes of substrate in tissue distribution, intracellular location, optimum pH, perinatal development and induction by organ culture or by phenobarbital. 3. Certain differences were noted between the two types of activity in behaviour on storage and on activation, in kinetic behaviour and in distribution between Wistar and Gunn rats; the Gunn rats were not deficient in hepatic UDP-glucuronyltransferase activity towards o-aminothiophenol. 4. These differences are no greater than those exhibited in the synthesis of various O-glucuronides; therefore thiolic substrates could compete in vivo with phenolic compounds for access to the UDP-glucuronyltransferase complex as well as for UDP-glucuronic acid.

Aging↗
PubMed1972

Mechanism of biosynthesis of thio- -D-glucuronides and thio- -D-glucosides.

1. The thio-beta-d-glucosiduronic acids (thio-beta-glucuronides) of o-aminothiophenol, diethyldithiocarbamic acid, p-nitrothiophenol and thiophenol are formed biosynthetically in broken- and intact-cell preparations of mouse liver. 2. For this biosynthesis to occur in homogenates or microsomal fractions, UDP-glucuronic acid was required during incubation; glucose, glucuronic acid or UDP could not replace it. UDP was a product of the reaction. 3. The biosynthetic mechanism linking glucuronic acid to thiol and carbodithioic groups therefore requires UDP-glucuronyltransferase activity and resembles that forming the various types of O-glucuronides. 4. An analogous enzymic mechanism employing UDP-glucose synthesizes the thio-beta-d-glucosides of diethyldithiocarbamic acid and thiophenol in gut preparations of the mollusc Arion ater; this mechanism resembles that forming the O-glucosides. The thio-beta-d-glucosides are formed also in intact cells. 5. As expected from the distribution of O-glycosides, S-glucuronides of these aglycones were not detectable with the invertebrate, nor were the S-glucosides with the vertebrate. 6. Despite their similar biosyntheses, S- and O-beta-glycosides differ in susceptibility to hydrolysis by beta-glycosidases. Rat preputial-gland beta-glucuronidase hydrolysed thioglucuronides of o-aminothiophenol, diethyldithiocarbamic acid and p-nitrothiophenol, hydrolysis being inhibited by glucarolactone; the thioglucuronide of thiophenol was not hydrolysed by preputial-gland or liver beta-glucuronidase. The two S-glucosides resisted hydrolysis by beta-glucosidase from almond emulsin.

Animals↗
PubMed1972

Development of phenobarbital-sensitive control mechanisms for uridine diphosphate glucuronyltransferase activity in chick embryo liver.

Uridine diphosphate (UDP) glucuronyltransferase activity in chick liver rises at hatching from near zero to adult levels. This rise will occur prematurely in embryo liver during organ culture. Increase in enzyme activity during organ culture differs with embryo age: in liver from 11-day old embryos it ceases at adult values; in liver from 5-day old embryos it continues to much higher-than-adult levels. Phenobarbital added to culture medium accelerates these rises in enzyme activity and elevates the plateau reached in 11-day embryo liver to that observed in 5-day embryo liver. Kinetic analysis of the changes in enzyme activity induced by phenobarbital during culture suggests that the regulatory mechanisms for enzyme activity are different in 5- and 11-day embryo liver and that these differences reflect developmental changes occurring in ovo.

Age Factors↗
PubMed1967

Development of uridine diphosphate-glucuronyltransferase activity in cultures of chick-embryo liver.

1. The liver of the domestric fowl (Gallus gallus) remains capable of conjugating o-aminophenol with glucuronic acid after 8 days' culture. The pathway of o-aminophenyl glucuronide formation in cultured liver, as in fresh tissue, includes the enzyme UDP-glucuronyltransferase. 2. UDP-glucuronyltransferase activity in chick-embryo liver increases on culture from very low to adult values within 6-8 days. 3. The development of UDP-glucuronyltransferase activity in cultured chick-embryo liver requires certain serum factors in the medium. The requirements change with embryo age. Liver from embryos younger than 15 days develops enzyme activity equally well in media containing either foetal or adult serum; liver from embryos older than 16 days develops activity only with adult serum. The development of enzyme activity in liver from the older embryos appears to be stimulated by diffusible factors in adult serum and inhibited by diffusible factors in foetal serum. It is suggested that the stimulation and inhibition of enzyme formation by small, diffusible molecules may be part of the mechanism regulating UDP-glucuronyltransferase activity in vivo. 4. Liver from 19-day-old chick embryos cultured with foetal serum begins to develop UDP-glucuronyltransferase activity if transferred to an adult-serum medium. Its capacity to develop UDP-glucuronyltransferase activity in adult serum survives in a foetal-serum medium for at least 5 days, the longest period tested. 5. The activity of UDP-glucuronyltransferase reached in 19-day chick-embryo liver after 1 or 2 days with adult serum is maintained without further increase after transfer to a foetal-serum medium. After 3 days with adult serum UDP-glucuronyltransferase activity continues to increase when the tissue is transferred to a foetal-serum medium. Thus liver from 19-day-old embryos requires 3 days with adult serum before development of enzyme activity becomes independent of a continuous adult-serum environment.

Aging↗
PubMed1966

The synthesis of o-aminophenyl glucuronide in several tissues of the domestic fowl, Gallus gallus, during development.

1. Synthesis of o-aminophenyl glucuronide has been studied in tissues of the domestic fowl, Gallus gallus, during development. 2. The only route of synthesis detected is glucuronyl transfer from UDP-glucuronic acid, and evidence suggests this to be the major pathway. 3. The pathway exists in liver, to a lesser extent in kidney and alimentary tract, and possibly also in skin. It is absent from spleen and adrenal gland. 4. o-Aminophenyl glucuronide formation, UDP-glucuronyltransferase, UDP-glucuronic acid and UDP-glucose dehydrogenase exist in the embryo liver from at least 12 days of incubation. Transferase activity falls just before hatching and rises suddenly on emergence. Overall synthesis of o-aminophenyl glucuronide observed in liver slices confirms this pattern, which also occurs in kidney. UDP-glucuronyltransferase appears in intestinal mucosa only after hatching, and is absent from embryonic spleen. The allantoic membrane forms no o-aminophenyl glucuronide. 5. These findings are related to the isolated existence of an avian embryo.

Adrenal Glands↗