Kinetic properties of different forms of hepatic UDP glucuronyltransferase
Biochimica et Biophysica Acta (BBA) - EnzymologyPublished 1 October 1972
Arnt Winsnes
Citations54
Generate an AI Snapshot to get a quick, structured summary of this paper.
Study Snapshot
ObjectiveStudy objective
MethodsResearch methodology
PopulationPopulation studied
Sample sizeSample sizes
OutcomesStudy outcomes here
ResultsStudy results comes here
LimitationsResearch study limitations comes here
A concise AI-generated summary of the paper will appear here once you click Generate AI Snapshot.
TL;DR
It is concluded that lecithin may have an important function in promoting a conformational change towards an enzyme form with better substrate affinity as a constituent of the microsomal membrane.
Abstract
1. Liver microsomes from mouse, rat and guinea pig were used for the enzyme source in the study of p-nitrophenol and o-aminophenol glucuronidation at varying UDPglucuronate concentrations and a fixed concentration of acceptor substrate. 2. In the case of p-nitrophenol glucuronyltransferase (UDPglucuronate glucuronyltransferase (acceptor-unspecific), EC 2.4.1.17) abrupt transitions in the Lineweaver-Burk plots (indicating negative cooperativity) were obtained with "native", frozen, sonicated, phospholipase C (EC 3.1.4.3) digested and detergent-treated microsomes from mouse and rat liver. With guinea pig microsomes most double-reciprocal plots were linear. The UDP-N-acetylglucosamine-activated enzyme also exhibited typical linear Lineweaver-Burk plots with mouse liver microsomes. 3. When o-aminophenol served as acceptor, linear Lineweaver-Burk plots were obtained in all instances except with frozen mouse liver microsomes as enzyme source. 4. UDP-N-acetylglucosamine treatment, freezing, sonication, phospholipase C digestion and detergent treatment of microsomes resulted in the activation of glucuronyltransferase at V as well as substantial increases in apparent KUDPglucuronate values. 5. The apparent KUDPglucuronate values increased 7–20-fold as a result of phospholipase C treatment of microsomes. Addition of lecithin micelles to such preparations lowered the apparent KUDPglucuronate markedly, but did not reverse the activation at V. It is concluded that lecithin may have an important function in promoting a conformational change towards an enzyme form with better substrate affinity. As a constituent of the microsomal membrane, however, lecithin also seems important for the postulated masking of active sites of glucuronyltransferase.
Keywords
MedicineBiochemistry, Genetics and Molecular BiologyPharmacology, Toxicology and Pharmaceutics
BiochemistryMultiple cyclic nucleotide phosphodiesterase activities from rat brain
1,062 Citations1971M. Michael Appleman, W. J. Thompson
BiochemistryMembrane formation in Tetrahymena pyriformis. 4. Lipid composition and biochemical properties of Tetrahymena pyriformis membrane systems
675 Citations1971Guy A. Thompson, Raymond J. Bambery +1 more
BiochemistryNegative cooperativity in enzyme action. Binding of diphosphopyridine nucleotide to glyceraldehyde-3-phosphate dehydrogenase
458 Citations1968Abby. Conway, Daniel E. Koshland
Journal of Biological ChemistrySarcoplasmic Reticulum
347 Citations1968A. Martonosi, J. R. Donley +1 more
Treatment of skeletal muscle microsomes with phospholipase C inhibits the adenosine triphosphatase activity and calcium transport, parallel with the selective hydrolysis of membrane lecithin, and is accompanied by tight binding ofospholipids to the microsomal membrane.
European Journal of BiochemistryThe Trapping of Uridine Phosphates by<scp>d</scp>‐Galactosamine,<scp>d</scp>‐Glucosamine, and 2‐Deoxy‐<scp>d</scp>‐galactose
298 Citations1970Dietrich Keppler, J. Rudigier +2 more
Observations contribute to an understanding of the orotate-mediated prevention of the galactosamine-induced liver damage, and of the role of pyrimidine nucleotides in this experimental hepatitis.
Journal of Biological ChemistryRegulation of Microsomal Enzymes by Phospholipids
207 Citations1971Donald A. Vessey, David Zakim
The activation of UDP-glucuronyltransferase in these experiments cannot be attributed to compartmentation of the enzyme but is due to phospholipid-induced alterations of enzyme conformation.
Biochimica et Biophysica Acta (BBA) - EnzymologyStudies on the activation in vitro of glucuronyltranferase
200 Citations1969Arnt Winsnes
Results are compatible with an activation by preincubation, detergents and UDP-N-acetylglucosamine due to exposition of active sites of glucuronyltransferases that have been nonfunctioning in unactivated tissue homogenates.
Journal of Biological ChemistryStudies on the Phospholipid Requirement of Glucose 6-Phosphatase
189 Citations1968Sue M. Duttera, William L. Byrne +1 more
The phospholipase A products have contradictory effects on glucose 6-phosphatase activity, and Lysolecithin, a trace component in microsomes, was the most effective phospholIPid in reactivation at low concentrations, but inhibited at higher levels.
Journal of Biological ChemistryA Requirement for Lipids by the Microsomal Stearyl Coenzyme A Desaturase
158 Citations1969Paul D. Jones, P.W. Holloway +2 more
The similarities between the lipid requirements of the DPNH-cytochrome c reductase and the stearyl-CoA desaturase support the suggestion that the two systems share a common electron transfer pathway or carrier.
Archives of Biochemistry and BiophysicsSpontaneous and detergent activation of a glucuronyltransferase in vitro
121 Citations1967Kira K. Lueders, Edward L. Kuff
Microsomal glucuronyltransferase catalyzing formation of p-nitrophenyl glucuronide in rat, guinea pig, and mouse livers, and transplantable rat hepatomas, was activated spontaneously during storage at 0 ° and by low concentrations of deoxycholate and Triton X-100 added in vitro.
Journal of Biological ChemistryA Requirement for Phospholipids by the Microsomal Reduced Diphosphopyridine Nucleotide-Cytochrome c Reductase
110 Citations1967Peter D. Jones, Salih J. Wakil
It is shown that lipids may be required for the transfer of electrons in the region beyond the flavoprotein of the DPNH-cytochrome c reductase system of intact microsomes, and when ferricyanide was used as the electron acceptor, no such lipid requirement could be demonstrated.
Biochemical JournalThe effect of phenobarbital on the submicrosomal distribution of uridine diphosphate glucuronyltransferase from rat liver
98 Citations1970Gerard J. Mulder
The latency of the enzyme in vitro, as shown by the effect of the detergent Triton X-100, is discussed in relation to the proposed heterogeneity of UDP glucuronyltransferase.
Archives of Biochemistry and BiophysicsMicrosomal rat liver UDP glucuronyltransferase: Effects of piperonyl butoxide and other factors on enzyme activity
97 Citations1971George W. Lucier, Otelia S. McDaniel +1 more
1-Naphthol and p -nitrophenol were shown to be glucuronidated by the same enzyme by of the mixed substrate method, divalent cation requirements, activation by detergent or ageing, submicrosomal distributions, levels of induction by piperonyl butoxide, and gravitational studies.
Molecular PharmacologyRole of Phospholipids in the Hepatic Microsomal Drug-Metabolizing System
85 Citations1970M. D. Chaplin, Gilbert J. Mannering
These studies provide further evidence that the type I and type II binding sites differ and that thetype I binding site is associated with membrane phospholipids, and show that type I binding is not required for the oxidation of type I compounds by microsomal enzymes.
Biochemical and Biophysical Research CommunicationsThe phospholipid-dependence of UDP-glucuronyltransferase
74 Citations1969Allan B. Graham, G. C. Wood
It is considered that the activity of the enzyme depends on phospholipids and hence, probably, on the structural integrity of the microsomal membrane.
Journal of Lipid ResearchPhenobarbital-induced alterations in phosphatidylcholine and triglyceride synthesis in hepatic endoplasmic reticulum
70 Citations1971David Young, Geraldine K. Powell +1 more
In vitro enzyme studies indicate that the increase in phosphatidylcholine content of phenobarbital-induced proliferating endoplasmic reticulum is related to increased activity of the pathway of phosphatidocholine biosynthesis involving the sequential methylation ofosphatidylethanolamine.
Biochemical JournalA role for phospholipids in the binding and metabolism of drugs by hepatic microsomes. Use of the fluorescent hydrophobic probe 1-anilinonaphthalene-8-sulphonate
68 Citations1971Thomas E. Eling, Richard P. DiAugustine
It was postulated that phospholipids have a permissive role in the metabolism of most drugs by hepatic microsomes and that the ANS probe might reflect interactions of compounds with microsomal membrane phospholIPids.
Pediatric ResearchBilirubin Uridine Diphospho-glucuronyltransferase in Rat Liver Microsomes: Genetic Variation and Maturation
66 Citations1971Leon Strebel, Gerard B. Odell
Results suggested that bilirubin monoglucuronide can be intermediate to the formation of bilirUBin diglucuronid, and may permit more precise differential diagnosis of retention jaundice of infancy and childhood and especially the “physiologic” jaundices of the newborn.
Biochimica et Biophysica Acta (BBA) - EnzymologyStudies on bilirubin UDP-glucuronyltransferase
60 Citations1967Elias Halac, Albert Reff
Kinetic data obtained with activated microsomes, and fractionation and inactivation experiments performed with deoxycholate-solubilized enzyme have yielded evidence in favor of the existence of at least two UDP-glucuronyltransferases.
Biochimica et Biophysica Acta (BBA) - EnzymologyPartial purification of hepatic UDP-glucuronyltransferase: Studies of some of its properties
51 Citations1970A P Mowat, Irwin M. Arias
Application of the purification procedure to livers of cat, Gunn rat and hypophysectomized or thyroidectomized rats also yielded a stable purified enzyme preparation, without separating conjugating ability for the substrates tested.
Biochemical JournalSOME DIFFERENCES IN THE CONJUGATION OF <i>O</i>-AMINOPHENOL AND <i>P</i>-NITROPHENOL BY THE URIDINE DIPHOSPHATE TRANSGLUCURONYLASE OF MOUSE-LIVER HOMOGENATES
45 Citations1965I. D. E. Storey
The results are discussed as suggesting that there are at least two uridine diphosphate transglucuronylases and that the o-aminophenol system was much more readily inhibited by all compounds than the p-nitrophenol system.
Biochemical JournalThe phospholipid-dependence of uridine diphosphate glucuronyltransferase. Reactivation of phospholipase A-inactivated enzyme by phospholipids and detergents
42 Citations1971David Attwood, Allan B. Graham +1 more
It is concluded that the reactivation by phospholipids is phosphatidylcholine-specific, and that high positive or negative zeta-potentials were correlated with the ability of the amphipathic compound to inactivate glucuronyltransferase.
Biochemical JournalMeasurement of uridine diphosphate glucuronic acid concentrations and synthesis in animal tissues
42 Citations1970V. Zhivkov
The concentration of UDP-glucuronic acid was higher in the liver of rats, rabbits and guinea pigs than in the same tissue of some species of birds, amphibia and fishes; also, the concentration in rat liver, kidney and small intestine was several times lower than that of the same tissues of Guinea pigs.
Archives of Biochemistry and BiophysicsActivation of tyrosinase in microsomes and melanosomes from B16 and Harding-Passey melanomas
40 Citations1970I. A. Menon, Herbert F. Haberman
Results indicate that tyrosinase in B16 and Harding-Passey melanomas is normally present in a latent state and could be increased significantly by procedures such as freezing and thawing, sonication, treatment with sodium deoxycholate, digitonin, sodium lauryl sulfate and Triton-X 100.
Chemico-Biological InteractionsActivation of microsomal UDP glucuronyltransferase by phospholipases
40 Citations1971Otto Hänninen, Raija Puukka
The digestion of microsomal membranes (from rat liver) with purified phospholipase A or C was found to increase severalfold the measurable UDP glucuronyltransferase activity in the membranes without solubilizing the enzyme.
Life SciencesActivation in vitro of rat hepatic UDP-glucuronyltransferase by ultrasound
34 Citations1970P.Th. Henderson
Kinetic studies at varying acceptor and UDPglucuronate concentrations demonstrate that ultrasonic treatment of the liver homogenate results in a significant increase of the apparent Km-values for UDPglUCuronyltransferase.
Biochemical JournalProperties of Lubrol-extracted uridine diphosphate glucuronyltransferase
27 Citations1971Richard D. Howland, Alan Burkhalter +3 more
The characteristics of the conjugation of the two phenols were found to differ with respect to pH optimum, bivalent cation requirement and Michaelis constants, suggesting that more than one enzyme is involved in the conjUGation reaction.
Biochimica et Biophysica Acta (BBA) - EnzymologyThe effects of sulfhydryl reacting agents on hepatic UDP-glucuronyltransferase in vitro
27 Citations1971Arnt Winsnes
The present report indicates that the active site of glucuronyltransferase is not dependent on sulfhydryl groups for catalysis, and the activating effect of UDP- N -acetylglucosamine was very sensitive towards such treatment.
Biochemical PharmacologyAge and sex dependent variability of the activation characteristics of UDP-glucuronyltransferase in vitro
27 Citations1971Arnt Winsnes
The observation that the activation characteristics of glucuronyltransferase in vitro vary with the age and the sex of the animal points towards an importance of the activation in vitro beyond its ability to increase the sensitivity of the enzyme assay, and raises the question of what assay conditions should be used to determine the functional level of glucURonyl transferase in vivo.
Journal of Biological ChemistryPartial Purification and Kinetic Properties of a Soluble Estrogen Glucuronyltransferase from Pig Intestine
26 Citations1969Govind S. Rao, Heinz Breuer
A soluble enzyme from the small intestine of the pig, capable of conjugating uridine diphosphate glucuronic acid with 17β-estradiol, has been purified 5- to 10-fold, and it is likely that only one enzyme catalyzes the glucuronidation of both 17 β-ESTradiol and estrone.
Biochemical PharmacologyVariable effect of phenobarbital treatment of mice on hepatic UDP-glucuronyltrans-ferase activity when judged by slightly different enzyme-assay techniques
25 Citations1971Arnt Winsnes
The results stress the importance of doing parallel studies of both non-activated and detergent-activated enzyme, as differences in the enzyme-assay techniques employed could be responsible for discrepancies.
Biochemical JournalThe effect of steroids and nucleotides on solubilized bilirubin uridine diphosphate glucuronyltransferase
24 Citations1970B.P.F. Adlard, G. H. Lathe
It was confirmed that bilirubin glucuronyltransferase can be obtained in solubilized form from rat liver microsomes and the competitive effects of stilboestrol, oestrone sulphate and 3beta-hydroxyandrost-5-en-17-one, with respect to UDP-glucuronic acid, may be explained on an allosteric basis.
Experimental Cell ResearchActivation by freezing of (Na + K)-ATPase in a microsomal fraction from ox kidney cortex
20 Citations1971Olaf Møller
It is concluded that the activation by freezing is due to an opening of closed vesicles whereby more enzyme sites are made available for the substrate.
Biochimica et Biophysica Acta (BBA) - EnzymologyAssay of UDPGlcUA pyrophosphatase and its relation to transglucuronidation
19 Citations1970Kim Ping Wong, Yeo Kok Lau
There is an inverse relationship between the hepatic activities of the pyrophosphatase and glucuronyltransferase in four species of animals and the reduction in the rate of transglucuronidation by the interfering pyroph phosphatase was most significant in rat liver homogenate.
Archives of Biochemistry and BiophysicsRegulation of microsomal enzymes by phospholipids
17 Citations1972David Zakim, Donald A. Vessey
Relatively high concentrations of organic mercurials react with a third type of -SH group (Type 3) to produce a deactivated form of UDPglycuronyltransferase, which renders the enzyme unstable at 37 ° in the absence of substrates.
Biochemical JournalStudies on a testosterone glucuronyltransferase from the cytosol fraction of human liver
14 Citations1970Govind S. Rao, Marie Luise Rao +1 more
The present findings suggest that testosterone and oestriol are conjugated by two separate enzymes.
Biochemical JournalFactors affecting the activity of oestradiol hydroxylase in rat liver microsomal subfractions
7 Citations1971B.J. Brown, Peter H. Jellinck
It is proposed that this polyamine acts either by direct activation of the enzyme complex or by inhibition of the lipid peroxidase pathway in a linked system rather than by stabilization of the reticular membranes.