Β-Glucuronidases IN METABOLIC HYDROLYSIS

Wakabayashi, Masao

doi:10.1016/b978-0-12-257602-7.50016-0

Cited by 15 publications

(6 citation statements)

References 278 publications

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“…In contrast, when expressed as tissue concentration, the activity of Cat D, but not that of GUase, was significantly elevated. In degenerative processes such as those following vitamin E deficiency or irradiation, decreased GUase activity has been recorded (35). The mechanisms of protein degradation in influenza are not clear, but reduced proteinsynthesizing capacity, as reflected by the abrupt decrease of RNA at a normal or even slightly increased protein degradation rate, seems to fit our data best.…”

Section: Discussionsupporting

confidence: 53%

Sequential metabolic alterations in the myocardium during influenza and tularemia in mice

Ilbäck¹,

Friman²,

Beisel³

et al. 1984

Infect Immun

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Mice with generalized influenza or tularemia of similar lethality were studied in an effort to compare biochemical responses of the myocardium during infections of viral and bacterial etiology. A progressive loss of body weight characterized the course of both infections. Accompanying this, the myocardial content of protein and the activities of lactate dehydrogenase, citrate synthase, and cytochrome c oxidase all decreased. However, myocardial protein degradation appeared earlier and was more pronounced in influenza, and the protein changes were accompanied by a rapid decline of myocardial RNA. Activation of acid hydrolases, such as cathepsin D and 0-glucuronidase, occurred in tularemia but not in influenza, whereas leakage of ,

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Section: Discussionsupporting

confidence: 53%

Sequential metabolic alterations in the myocardium during influenza and tularemia in mice

Ilbäck¹,

Friman²,

Beisel³

et al. 1984

Infect Immun

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“…Human β-glucuronidase has been found in all mammalian tissues and body fluids, with the highest activity in kidney, spleen, epididymis, liver, cancer tissue, and the gastrointestinal tract, which is distinct from the β-glucuronidase produced by gastrointestinal tract microorganisms (Marsh et al 1952; Levvy 1960; Wakabayashi 1970). One third of the β-glucuronidase found in liver cells is localized in the endoplasmic reticulum, whereas the remaining two thirds is found in the lysosome (Swank et al 1986).…”

Section: Introductionmentioning

confidence: 99%

“…The primary β-glucuronidase inhibitor used for in vitro assays is D-saccharic acid 1,4-lactone (saccharolactone), which was discovered by Levvy in 1952 to competitively inhibit the enzyme (Levvy 1952). Several other β-glucuronidase inhibitors have been identified including polymeric phosphates of diethystibestrol, dienestrol, hexesterol, and benzeterol and some heavy metals (Cu +2 , Ag +2 , Hg +2 ) (Wakabayashi 1970). However, these inhibitors are not selective for β-glucuronidase, and are not used in routine microsomal glucuronidation assays.…”

Section: Introductionmentioning

confidence: 99%

Effect of the β-glucuronidase inhibitor saccharolactone on glucuronidation by human tissue microsomes and recombinant UDP-glucuronosyltransferases

Oleson

Court

2008

Journal of Pharmacy and Pharmacology

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Glucuronidation studies using microsomes and recombinant UDP-glucuronosyltransferases (rUGTs) can be complicated by the presence of endogenous β-glucuronidases leading to underestimation of glucuronide formation rates. Saccharolactone is the most frequently used β-glucuronidase inhibitor, although as of yet it is not clear whether this reagent should be routinely added to glucuronidation incubations. Here we determined the effect of saccharolactone on eight different UGT probe activities using pooled human liver microsomes (pHLMs) and rUGTs. Despite the use of buffered incubation solutions it was necessary to adjust the pH of saccharolactone solutions to avoid effects (enhancement or inhibition) of lowered pH on UGT activity. Saccharolactone at concentrations ranging from 1 to 20 mM failed to show enhancement of any of the glucuronidation activities evaluated that could be considered consistent with inhibition of β-glucuronidase. However, for most activities, higher saccharolactone concentrations resulted in a modest degree of inhibition. The greatest inhibitory effect was observed for 5-hydroxytryptamine and estradiol glucuronidation by pHLMs with 35% decrease at 20 mM saccharolactone concentration. Endogenous β-glucuronidase activities were also measured using various human tissue microsomes and rUGTs with estradiol-3-glucuronide and estradiol-17-glucuronide as substrates. Glucuronide hydrolysis was observed for pHLMs, lung microsomes, and insect-cell expressed rUGTs, but not for kidney or intestinal microsomes, or HEK293 microsomes. However, the extent of hydrolysis was relatively small representing only 9 to 19% of the glucuronide formation rate measured in the same preparations. Consequently, these data do not support the routine inclusion of saccharolactone in glucuronidation incubations and, if used, saccharolactone concentrations should be titrated to achieve activity enhancement without inhibition.

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“…,8-glucuronidase has beeni the most extensively studied (for review see Wakabayashi [2]). Changes in the urinary level of this enzyme have been reported in a variety of pathological states, including urinary tract infection (3)(4)(5)(6), renial disease (7), transplantation rejection (8), protein-calorie malnutrition (9), epilepsy (10), and neoplasms of the bladder (11), testes (12), larynx (12), and breast (12).…”

Section: Introductionmentioning

confidence: 99%

Coordinacy of lysosomal enzyme excretion in human urine.

Paigen¹,

Peterson²

1978

J. Clin. Invest.

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A B S T R A C T Assay conditions have been developed for the determination of urinary 8-glucuronidase, ,8-galactosidase, a-galactosidase, and, -hexosaminidase using fluorometric substrates. The assay conditions for ,8-glucuronidase overcome interference by both low and high molecular weight inhibitors, a problem that has confused earlier studies of enzyme excretion.The fouir lysosomal enzymes are excreted coordinately; although their absolute levels (in units per milligram of creatinine) vary during the day and from one day to the next, the ratio of one enzyme to another remains relatively constant. The lack of correlationi between plasma aind urine enzyme levels, together with the high molecular weights of these enzymes, suggests that the urinary enzymes are not derived by glomerular filtration. The lack of coordinacy with lactate dehydrogenase suggests they are not derived from exfoliated cells. By analogy with experimental animals, they' may be derived from lysosomes extruded into the lumnen of the proxinmal tubule by epithelial cells.There is considerable variation among a poptulation of 125 healthy adult subjects for total enzyme exeretionl. Both total enzyme excretion and coordinacy ratios are log-normially' distributed, suggesting that they are the resuiltants of many factors, each of which has a relative, or proportional, effect on enzyme excretion. About one-half the population variation resides in a process common to the exeretion of all four enzymes (possibly the lsosomiie extruisioni pathway'), and about one-half r-esides in factors affectiing each enzviye independently.

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Β-Glucuronidases IN METABOLIC HYDROLYSIS

Cited by 15 publications

References 278 publications

Sequential metabolic alterations in the myocardium during influenza and tularemia in mice

Sequential metabolic alterations in the myocardium during influenza and tularemia in mice

Effect of the β-glucuronidase inhibitor saccharolactone on glucuronidation by human tissue microsomes and recombinant UDP-glucuronosyltransferases

Coordinacy of lysosomal enzyme excretion in human urine.

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