Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.17.21 (prostate-specific membrane antigen)
 1,761 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After ingestion of synthetic PteGlu3 in physiological doses, the folate forms were studied in plasma obtained from human vena portae blood. Plasma conjugase was inhibited by rapid heat-denaturation. The folate forms were assayed with L. casei and S. faecalis and identified by thin-layer chromatography (biautography). Mono- and diglutamic folate was demonstrated in the portal plasma, indicating that intestinal hydrolysis precedes the absorption of conjugated folates. The pteroylpolyglutamate hydrolase activity in the human gastrointestinal tract was investigated. The activity was demonstrated in gastric juice, pancreatic juice, and intestinal mucosa. The highest activity was found in the pancreatic juice with a pH-optimum of 4.5. In gastric juice the pH-optimum for the enzyme was 3 and the activity half of that found in pancreatic juice. However, in view of the volumes of these fluids produced every day, the activity at physiological pH might be enough to hydrolyse the daily intake of conjugated folates in amounts of about 500 mug.
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PMID:The hydrolysis and absorption of conjugated folates in man. 0 71

Studies were conducted to determine the in vitro effect of selected food components on activity of the brush border membrane pteroylpolyglutamate hydrolase (folate conjugase) of porcine and human intestine. Foods differed widely in their effects although the pattern of the effects on both porcine and human enzymes was similar. Extracts of legumes, tomatoes, and orange juice consistently inhibited the conjugase activity. Citrate was also inhibitory to some extent. In contrast, extracts of cereal grain flours, whole egg, milk, cabbage, cauliflower, and lettuce caused little inhibition. Purified phytohemagglutinins, soybean trypsin inhibitors, and bovine milk folate-binding protein had no effect on the conjugase activity at the concentrations tested. The food substances that inhibited the conjugase activity did not bind the polyglutamyl folate substrate or inhibit intestinal brush border membrane sucrase and alkaline phosphatase. These findings suggest that food composition may influence folate bioavailability by interfering with the intestinal deconjugation of dietary polyglutamyl folates.
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PMID:Inhibition by selected food components of human and porcine intestinal pteroylpolyglutamate hydrolase activity. 229 33

The activity of folate conjugase (pteroylpolyglutamate hydrolase, EC 3.4.22.12) was measured in plasma from normal subjects and patients with breast cancer using pteroylglutamyl-gamma-glutamyl-gamma-(U14C) glutamate as the substrate. Conjugase assays also were performed on samples of breast-tumor tissue, normal breast, and fibroadenoma. When assayed at pH 4.5 and 7.4, mean plasma conjugase activity was significantly (p less than 0.05) elevated in a group of patients with anatomically proven metastatic disease (n = 21) when compared with control subjects (n = 12) and a group of patients (n = 13) with no clinical evidence of disease after mastectomies. Mean plasma conjugase activity assayed at pH 4.5 also was significantly higher in the metastatic disease group when compared with breast cancer patients before mastectomy (n = 9) and fibroadenoma patients before biopsy (n = 3). The specific activity of tissue conjugase assayed at pH 4.5 was significantly higher (p less than or equal to 0.05) in infiltrating ductal carcinoma than in normal adjacent breast tissue according to the Wilcoxon test for paired samples (n = 10).
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PMID:Folate conjugase activity in the plasma and tumors of breast-cancer patients. 303 25

Phosphonate and phosphinate analogues of N-acylated gamma-glutamylglutamate were tested for the ability to inhibit glutamate carboxypeptidase II (GCP II). All of the compounds inhibit GCP II with IC(50) values in the low nanomolar range. The comparison of the results to previously reported inhibitory studies of the same compounds toward folylpoly-gamma-glutamyl synthetase (FPGS) and gamma-glutamyl hydrolase (gamma-GH) provides insight into structural and mechanistic features of each enzyme. Potential utility of these compounds as diagnostic agents and probes to understand folate or antifolate poly-gamma-glutamates metabolism is also described.
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PMID:Phosphonate and phosphinate analogues of N-acylated gamma-glutamylglutamate. potent inhibitors of glutamate carboxypeptidase II. 1212 34

Dietary polyglutamyl folates are hydrolyzed to monoglutamyl folate derivatives prior to intestinal transport. In humans and pigs, the reaction occurs at pH 6.5 at the jejunal brush border membrane by folate hydrolase and is encoded by the glutamate carboxypeptidase II (GCPII) gene. Intracellular folate hydrolase with an optimal pH of 4.5 is encoded by the gamma-glutamyl hydrolase (gamma-GH) gene and predominates in rats. We determined the respective roles of GCPII and gamma-GH in dietary folate hydrolysis in rat small intestine. Duodenal, jejunal, and ileal mucosa, pancreas, and duodenal luminal fluid were collected from 10 Sprague-Dawley rats that had not been food deprived. Folate hydrolase was assayed at pH 4.5 and 6.5 with and without parahydroxymercuribenzoate (pHMB), an inhibitor of intracellular folate hydrolase. Folate hydrolase activity occurred at pH 4.5 in all tissues, was significantly inhibited by the addition of pHMB at both pH 4.5 and 6.5, and was virtually absent from brush border fractions at pH 6.5. The highest activity was in the postprandial duodenal luminal fluid at pH 4.5. Rat-specific primers for GCPII and gamma-GH were used to detect mRNA expression in pancreas, jejunal mucosa, and liver. GCPII expression was detected only in the liver, whereas gamma-GH was expressed in all 3 tissues. These results suggest that the hydrolysis of polyglutamyl folates in rats requires the intracellular folate hydrolase that is expressed by pancreatic gamma-GH, in contrast to GCPII that is expressed in the jejunal mucosal brush border in pigs and humans. gamma-GH folate hydrolase is abundant in rat postprandial pancreatic secretions and appears to hydrolyze dietary folates in the intestinal lumen prior to intestinal absorption.
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PMID:gamma-Glutamyl hydrolase, not glutamate carboxypeptidase II, hydrolyzes dietary folate in rat small intestine. 1744 73