Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.31 (beta-glucuronidase)
 7,680 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence has been presented suggesting the presence of vitamin D(3) 3beta-glucosiduronate and 1,25-dihydroxyvitamin D(3) glucosiduronate in rat bile. To evaluate the role of vitamin D glucosiduronates in calcium and phosphorus homeostasis, we synthesized vitamin D(3) 3beta-glucosiduronate and tested its biological activity in calcium- and vitamin D-deficient rats. After the intravenous administration of vitamin D(3) 3beta-glucosiduronate to rats maintained on a low calcium diet, there was an increase in duodenal calcium transport and an increase in serum calcium. Vitamin D(3) 3beta-glucosiduronate, however, was less active than equimolar amounts of vitamin D(3). At doses of less than 0.65-1 nmol per rat, the conjugate exhibited no activity. When vitamin D(3) 3beta-glucosiduronate was administered to vitamin D-deficient rats, 25-hydroxyvitamin D was detected in the serum; the increase in serum 25-hydroxyvitamin D levels was less than that observed after the administration of an equimolar amount of vitamin D(3). Vitamin D(3) 3beta-glucosiduronate showed no detectable activity in the induction of calcium binding protein in chick embryonic duodena, a system in which no endogenous steroid beta-glucuronidase activity is detectable. These data demonstrate that vitamin D(3) 3beta-glucosiduronate is biologically active in vivo and that the observed activity is due to hydrolysis of the conjugate to vitamin D(3). As vitamin D(3) 3beta-glucosiduronate is excreted in the bile of rats, it is possible that this conjugate is reutilized in vivo after hydrolysis to free vitamin D(3). These results suggest the existence of a mechanism for reutilization of the biliary products of vitamin D(3).
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PMID:Role of vitamin D glucosiduronate in calcium homeostasis. 625 10

Young rats, fed a low calcium and vitamin D deficient diet for 2 weeks, developed hypocalcemia, an increased activity of serum alkaline phosphatase and an increase in the serum concentration of immunoreactive parathyroid hormone. An increased activity of lactate dehydrogenase and cytochrome oxidase in odontoblasts was found. No shift in the general energy metabolic pathway was found as visualized in the lactate dehydrogenase iso-enzyme pattern. The dominating lactate dehydrogenase isoenzyme in odontoblasts from both the normal and the deficient rats was LDH 1 (H4, LD5), thus indicating primarily an aerobic energy-metabolism Also the activities of the lysosomal enzymes acid phosphatase, cathepsin D and hyaluronidase in the odontoblasts from the deficient animals were increased when compared to the normal animals. No significant change could be demonstrated for beta-glucuronidase and beta-N-acetylglucosaminidase. It was earlier found that this deficient diet caused an increase in odontoblast alkaline phosphatase activities and protein synthesis in vitro. In view of the present findings it might be concluded that the low calcium and vitamin D deficient diet causes a general increase in the odontoblast metabolism. It is not known whether this is due to the increase in parathyroid hormone or if it is a direct effect of the lowered serum calcium concentration.
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PMID:Odontoblast metabolism in rats deficient in vitamin D and calcium. IV. Lysosomal and energy metabolic enzymes. 625 18

The effect of the calcium antagonist verapamil on 1 alpha-hydroxy-vitamin D3 (1 alpha (OH)D3) stimulated bone resorption in tissue culture has been investigated. It was found that verapamil in concentrations above 20 mumol/l reduced 1 alpha (OH)D3-stimulated mineral mobilization, as measured by release of in vivo incorporated 45Ca from mouse calvarial bones. The inhibition of verapamil could be seen already 3 h after exposure to the drug. The increased degradation by 1 alpha (OH)D3 of the organic matrix in the calvaria, as assessed by the release of in vivo 3H-proline labelled collagen, was also reduced by verapamil. The inhibitory effect of the drug on 45Ca release was reversible after withdrawal. 1 alpha (OH)D3 increased the release of stable calcium and beta-glucuronidase, and these effects could be blocked by verapamil. Increasing medium calcium concentration from 1.8 to 5 mmol/l slightly reduced the inhibitory capacity of 50 mumol/l verapamil on 1 alpha (OH)D3-stimulated 45Ca release. These data indicate that stimulation of osteoclasts by hydroxylated metabolites of vitamin D to resorb bone and secrete lysosomal enzyme is dependent on an increased availability of free intracellular calcium.
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PMID:Inhibition of 1 alpha-hydroxy-vitamin D3 stimulated bone resorption in tissue culture by the calcium antagonist verapamil. 680 91

The effect of 1 alpha-hydroxy-vitamin D-3 on the release of calcium (40Ca, 45Ca), inorganic phosphate and lysosomal enzymes, on glucose consumption and lactate production was studied in a bone organ culture system using half calvaria from 6--7-day-old mice. 1 alpha-Hydroxy-vitamin D-3 stimulated the mobilization of minerals and increased the release of beta-glucuronidase, beta-N-acetylglucosaminidase and acid phosphatase, while no effect on the release of lactate dehydrogenase was seen. 1 alpha-Hydroxy-vitamin D-3 also caused a significant increase in the total activities of acid phosphatase in the bones after culture, indicating increased enzyme synthesis. The stimulatory effect on the release of Pi and beta-glucuronidase was also obtained after a temporary exposure to 1 alpha-hydroxy-vitamin D-3. The stimulation by 1 alpha-hydroxy-vitamin D-3 on the release of Ca2+, Pi and beta-glucuronidase was suppressed by a protein synthesis inhibitor, cycloheximide. No effect by 1 alpha-hydroxy-vitamin D-3 on glucose consumption and lactate production was registered, suggesting that increased mineral mobilization does not require increased lactate production. It is concluded that although the data in the present paper do not prove a cause-and-effect relationship between lysosomal enzyme release and bone resorption, they give further support to the concept that the processes are intimately associated.
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PMID:Relationship between bone resorption and lysosomal enzyme release as demonstrated by the effect of 1 alpha-hydroxy-vitamin D-3 in an organ culture system. 741 23

The separation and characterization of vitamin D(3)- and 25-hydroxyvitamin D(3)-monoglucuronides, biliary metabolites obtained from rats dosed with D(3) and 25-hydroxyvitamin D(3) per os, respectively, were carried out by HPLC. The glucuronide fractions were obtained from bile specimens by the combined use of a Bond Elut C18 cartridge, for solid phase extraction, and a lipophilic gel (piperidinohydroxypropyl Sephadex LH-20), for ion-exchange chromatography. Each glucuronide was identified by comparison with an authentic sample in three ways: its chromatographic behavior, that of its fluorescent labeled derivative using 4-[4-(6-methoxy-2-benzoxazolyl)phenyl]-1,2,4-triazoline-3,5- dione and data obtained following enzymatic hydrolysis using beta-glucuronidase.
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PMID:Separation and characterization of monoglucuronides of vitamin D(3) and25-hydroxyvitamin D(3) in rat bile by high-performance liquid chromatography. 886 Sep 45

In vivo metabolism of 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) in female dogs has been studied thoroughly, and its major bile metabolite identified. After single oral administration of 24,25-(OH)2 [6,19,19-3H]D3 the plasma concentrations of radioactive metabolites were monitored for 504 h, and the metabolites in the bile collected and analyzed. The concentration of 24,25-(OH)2D3 in plasma reached a maximum after 6 h and decayed in two distinct phases; a fast-phase with a half-life of 17 h, followed by a slow-phase with a 17-day half-life. The area under the concentration/time curve (AUC) was 78-84% (0-504 h). The only detectable metabolite in the plasma was 25-hydroxy-24-oxovitamin D3 whose AUC was less than 5%. At 504 h, about 50% of administered radioactivity has been excreted, of which about 90% was found in the feces, indicating most of the administered 24,25-(OH)2D3 to be excreted in bile. A major metabolite, which constituted 23% of the total bile radioactivity at 504 h, was found in the bile. This metabolite was efficiently deconjugated by beta-glucuronidase to afford an aglycone which was identified as 23S,25-dihydroxy-24-oxovitamin D3 (23S,25-(OH)2-24-oxo-D3), by co-chromatography on HPLC with synthetic standards. The glucuronide was isolated from the bile of dogs given large doses of 24,25-(OH)2D3, and the structure determined being 23-(beta-glucuronide) of 23S,25-(OH)2-24-oxo-D3, by analyzing its negative ion mass spectrum and the positive ion mass spectrum of its derivatives. Thus it was concluded that, in dogs, 24,25-(OH)2D3 is a long lasting vitamin D metabolite, is mainly excreted in bile when metabolized to 23S,25-(OH)2-24-oxo-D3 and is conjugated at 23-OH as glucuronide.
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PMID:In vivo metabolism of 24R,25-dihydroxyvitamin D3: structure of its major bile metabolite. 921 97

The monoglucuronides of vitamin D, 25-hydroxyvitamin D and the corresponding pro-forms were subjected to enzymatic hydrolysis using beta-glucuronidase, and substrate specificities were found in the examined enzymes originating from different sources, which were determined using reversed-phase high-performance liquid chromatography with UV detection. The enzymatic hydrolysis of the corresponding monosulfates was also examined using the same system.
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PMID:Enzymatic hydrolysis of the conjugate of vitamin D and related compounds. 922 45

The characterization of the urinary metabolites of vitamin D(3) in man under physiological conditions was performed using liquid chromatography-tandem mass spectrometry (LC-MS-MS). The urine specimens obtained from healthy volunteers were treated with beta-glucuronidase, purified with disposal solid-phase extraction cartridges, derivatized with a Cookson-type reagent, 4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalyl)ethyl]-1,2,4-triazoline-3,5-dione, and subjected to LC-MS-MS. The derivatization was employed to increase the ionization efficiencies of the vitamin D(3) metabolites, which enabled detection of the metabolites in the picogram range. The identification of the genin parts of the metabolites was done by comparison with authentic samples based on their LC-MS-MS data. The glucuronides of 23S,25-dihydroxyvitamin D(3) and 24R,25-dihydroxyvitamin D(3) were obtained as the main metabolites from the urine in almost equal amounts. In contrast to the fact that the plasma/serum concentration of the former is much lower than that of the latter, the hydroxylation at the C-23 position was considered to be the important side-chain modification of 25(OH)D(3) to excrete the excess vitamin D(3) in man. In addition, 23S,25-dihydroxy-24-oxovitamin D(3) occurred as its glucuronide in most of the urine, which suggested that this metabolite also plays a part in the excretion of vitamin D(3) in man.
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PMID:Characterization of urinary metabolites of vitamin D(3) in man under physiological conditions using liquid chromatography-tandem mass spectrometry. 1209 29

Klotho gene mutation leads to a syndrome strangely resembling chronic kidney disease patients undergoing dialysis with multiple accelerated age-related disorders, including hypoactivity, sterility, skin thinning, muscle atrophy, osteoporosis, vascular calcifications, soft-tissue calcifications, defective hearing, thymus atrophy, pulmonary emphysema, ataxia, and abnormalities of the pituitary gland, as well as hypoglycemia, hyperphosphatemia, and paradoxically high-plasma calcitriol levels. Conversely, mice overexpressing klotho show an extended existence and a slow aging process through a mechanism that may involve the induction of a state of insulin and oxidant stress resistance. Two molecules are produced by the klotho gene, a membrane bound form and a circulating form. However, their precise biological roles and molecular functions have been only partly deciphered. Klotho can act as a circulating factor or hormone, which binds to a not yet identified high-affinity receptor and inhibits the intracellular insulin/insulin-like growth factor-1 (IGF-1) signaling cascade; klotho can function as a novel beta-glucuronidase, which deglycosylates steroid beta-glucuronides and the calcium channel transient receptor potential vallinoid-5 (TRPV5); as a cofactor essential for the stimulation of fibroblast growth factor (FGF) receptor by FGF23. The two last functions have propelled klotho to the group of key factors regulating mineral and vitamin D metabolism, and have also stimulated the interest of the nephrology community. The purpose of this review is to provide a nephrology-oriented overview of klotho and its potential implications in normal and altered renal function states.
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PMID:Klotho: an antiaging protein involved in mineral and vitamin D metabolism. 2241 41

The discovery that two recently identified molecules, klotho and fibroblast growth factor 23 (FGF23), played an important role in calcium, phosphate, and vitamin D metabolism has transformed our traditional physiological view in which bone and mineral homeostasis was mainly regulated by parathyroid hormone, vitamin D, and calcitonin, according to mineral body needs. FGF23 is a 251-amino acid secreted protein produced by osteoblasts and osteocytes in bone following the stimulation by phosphate and vitamin D or the inhibition by dentin matrix protein 1. Originally isolated from tumoral cells of patients with tumor-induced osteomalacia and hypophosphatemia, FGF23 inhibits phosphate reabsorption in renal proximal tubular cells and 1alpha-hydroxylase activity, resulting in decreased synthesis of calcitriol. To exert these actions, FGF23 requires the conversion, by klotho, of the canonical FGF receptor 1 (IIIc) in a specific high affinity FGF23 receptor. On the other hand, klotho is a putative antiaging gene identified in 1997 when a particular mouse strain, created by random insertion mutagenesis, was found to be short-lived and displayed premature atherosclerosis, osteopenia, skin atrophy, pulmonary emphysema, hyperphosphatemia, hypercalcemia, and high serum calcitriol levels. The gene of klotho encodes a 1012-amino acid cell-surface protein with a short cytoplasmic tail and an extracellular domain that consists in tandem duplicated copies of a beta-glucuronidase-like sequence, which can be released into the circulation as soluble forms after being cleaved by metalloproteinases such as ADAM10 and ADAM17. By modulating FGF23 action, klotho regulates urinary phosphate excretion and calcitriol synthesis. By virtue of its beta-glucuronidase activity, klotho deglycosylates the calcium channel TRPV5 (transient receptor potential vallinoid-5) and regulates urinary calcium excretion. klotho also binds to Na(+),K(+)-ATPase in parathyroid cells and regulates calcium-stimulated PTH secretion. Finally, klotho extends life span via several mechanisms, including the reduction of calcitriol synthesis, serum calcium, and phosphorus levels; the induction of insulin resistance; and by increasing the resistance to oxidative stress.
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PMID:Klotho gene, phosphocalcic metabolism, and survival in dialysis. 1912 71


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