Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Some important enzymes concerned with the biosynthesis of the precursors of glycosaminoglycans (gg), degradation of gg and biological sulphation have been studied in rats fed an atherogenic diet. L-Glutamine-D-fructose-6-phosphate amino-transferase and glucosamine-6-phosphate-N-acetylase--2 enzymes concerned with the biosynthesis of hexosamine precursors of gg--decreased in the liver in rats fed the atherogenic diet. UDPG pyrophosphorylase, UDPG dehydrogenase and UDPG glucuronic acid-5'-epimerase, which are concerned with the biosynthesis of the uronic precursors of gg, also decreased in the liver in the diet-fed rats. The activities of some of the enzymes concerned with degradation of gg-hyaluronidase, beta-glucuronidase beta-hexosaminidase, cathepsin and aryl sulphatase--increased both in the liver and aorta. The hepatic concentration of PAPS significantly decreased in the diet-fed rats. The sulphate-activating system, which includes ATP sulphurylase, APS kinase and sulphotransferase, also decreased. Thus the overall picture is one of decreased synthesis of gg and their increased degradation in the atheromatous rats.
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PMID:Metabolism of glycosaminoglycans in atheromatous rats. Enzymes concerned with synthesis, degradation and sulphation of glycosaminoglycans. 12 76

The effect of low and high doses of ascorbic acid on glycosaminoglycan and lipid metabolism was studied in guinea pigs fed both normal and atherogenic diets. The high dose of ascorbic acid (25 mg/100 g body weight/day) decreased the cholesterol level in the liver and aorta but not in the serum in animals fed the normal diet in comparison with those fed the low dose of ascorbic acid (0.1 mg/100 g body weight/day). In animals fed the atherogenic diet, cholesterol decreased in the serum and liver, but not in the aorta. Serum triglycerides were not affected by the dose of ascorbic acid in the group on the normal diet, but in the animals receiving the atherogenic diet, the high dose of ascorbic acid caused serum triglycerides to decrease when compared with the low dose. Hepatic and aortic triglycerides decreased in groups on normal and atherogenic diets receiving the high dose of ascorbic acid. Lipoprotein lipase activity was not affected in the aorta by the dose of ascorbic acid either in the normal or atherogenic diet group. It was increased in the liver and heart in both the groups receiving the low dose of ascorbic acid but decreased in the high dose group. The concentration of all the glycosaminoglycans significantly increased in the aorta of animals on normal diet receiving the high dose of ascorbic acid when compared with the low dose group. In the group on the atherogenic diet, hyaluronic acid was not affected, but all the sulphated glycosaminoglycans increased in the animals receiving the high dose when compared with those receiving the low dose. In the liver all the sulphated glycosaminoglycans increased while hyaluronic acid decreased in both the normal and atherogenic diet groups receiving the high rather than the low dose of ascorbic acid. L-Glutamine:D-fructose-6-phosphate aminotransferase and UDPG dehydrogenase, two key enzymes in the biosynthesis of precursors of glycosaminoglycans, were studied in relation to the dose of ascorbic acid. Hepatic aminotransferase activity was higher both in the normal and atherogenic diet groups when receiving the high rather than the low dose of ascorbic acid. UDPG dehydrogenase was not affected by the dose of ascorbic acid. The activities of the degrading enzymes -- hyaluronidase, beta-glucuronidase, beta-hexosaminidase and aryl sulphatase -- significantly increased both in the normal and atherogenic diet groups when receiving the low rather than the high dose of ascorbic acid. The concentration of PAPS, sulphate activity and sulphotransferase activity were all increased in both the normal and atherogenic diet groups receiving the high dose of ascorbic acid.
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PMID:Ascorbic acid and glycosaminoglycan and lipid metabolism in guinea pigs fed normal and atherogenic diets. 12 67

The polysaccharide from blackgram (Phaseolus mungo) has been previously reported to cause lower cholesterol, phospholipids and triglyceride levels in rats fed either low-or high-fat diets containing cholesterol. The effect of this polysaccharide fraction as compared to that of glucose and sucrose on the metabolism of glycosaminoglycans and glycoprotein has been studied. The pattern of change in the levels of different glycosaminoglycans varied in the different tissues. Sucrose fed animals gave lower levels of sulphated glycosaminoglycans in the aorta and liver. The polysaccharide and glucose fed animals gave comparable values in the aorta except in the case of chondroitin sulfate B which was higher and heparin lower in the polysaccharide group. L-glutamine:D-fructose-6-phosphate amino transferase and UDPG dehydrogenase were lowest in the sucrose fed animals and highest in the polysacchride group with the animals in the glucose group showing intermediate values, but UDPG pyrophosphorylase, while highest in the polysaccharide group, was similar in the glucose and sucrose groups. Some of the degrading enzymes studied-beta-glucuronidase, hyaluronidase and aryl sulphatase-were highest in the sucrose group and generally lowest in the polysaccharide group. Levels of 3'-phosphoadenosine-5'-phosphosulphate, the biological sulphating agent, the sulphate activating system which includes ATP sulphurylase and APS kinase and sulphotransferase activity were also lowest in the sucrose fed group and highest in the polysaccharide group. The glycoprotein concentration was highest in the liver and lowest in the kidney in the sucrose group.
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PMID:Nature of the dietary carbohydrate and metabolism of glycosaminoglycans and glycoproteins in rats. 17 34

The effect of orchidectomy in male rabbits and administration of testosterone to orchidectomized animals on the metabolism of glycosaminoglycans (GAG) has been studied. The response of the different GAG fractions in the aorta varies with the nature of the GAG, and in some cases is different in different segments of the aorta. Orchidectomy produced an increase in hyaluronic acid fraction, decrease in heparin sulphate fraction, and no response in the chondroitin sulphate A fraction in the aortic arch, thoracic aorta, and abdominal aorta. Chondroitin sulphate C and chondroitin sulphate B fractions decreased only in the abdominal aorta and were not significantly altered in the other two segments, while heparin fraction decreased only in the thoracic aorta and was not affected in the other segments. Administration of testosterone to the orchidectomized animals counteracted these changes in the aortic GAG fractures. The enzymes concerned with the synthesis of precursors of GAG--L-glutamine:D-fructose-6-phosphate aminotransferase, UDPG dehydrogenase, and UDPG pyrophosphorylase-- all decreased in the orchidectomized animals; testosterone administration increased their activity in the orchidectomized animals. Enzymes concerned with degradation of GAG--beta-glucuronidase, beta-hexosaminidase, aryl sulphatase, cathepsin, and hyaluronidase--increased in the orchidectomized and decreased on administration of testosterone. Concentration of PAPS and activity of sulphate-activating system and sulphotransferase also decreased in the orchidectomized animals, and testosterone administration tended to restore this decrease to normal levels.
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PMID:Sex hormones and metabolism of glycosaminoglycans. I. Effect of orchidectomy and administration of testosterone in rabbits. 99 37

The has operon is composed of three genes, hasA, hasB, and hasC that encode hyaluronate synthase, UDP-glucose dehydrogenase, and presumptively UDP-glucose pyrophosphorylase, respectively. Expression of the has operon was shown to be required for the synthesis of the hyaluronic acid capsule in group A streptococci. Previous studies indicated that some group A and group C streptococcal strains produce the hyaluronic acid capsule, while others do not. In addition, it was observed that encapsulated strains cultured in stationary phase of growth lose the hyaluronic acid capsule. Therefore, the molecular mechanisms controlling the expression of the hyaluronic acid capsule in group A streptococci was investigated. In this study, it was determined that all encapsulated and unencapsulated strains of group A streptococci as well as encapsulated group C streptococci analyzed possess the has operon locus. The acapsular phenotype was accounted for by the absence of hyaluronate synthase activity in the membrane and not the production of extracellular hyaluronidase. A has operon mRNA transcript was not expressed by unencapsulated strains of group A streptococci, whereas encapsulated strains of group A streptococci grown to mid to late exponential phase produced the hyaluronate capsule, as well as has operon mRNA. However, as the streptococci entered the stationary phase of growth, they became acapsular and this was concomitant with the loss of has operon mRNA transcript. These results were confirmed by primer extension analyses of RNA isolated from encapsulated and unencapsulated strains of group A streptococci as well as RNA prepared from encapsulated strains cultured in exponential and stationary phases of growth. Thus, the loss of has operon mRNA in unencapsulated group A streptococci, as well as growth phase regulation occurs at the previously mapped has operon promoter. These data suggested that the synthesis of the hyaluronic acid capsule for group A streptococci may be controlled by transcriptional mechanisms.
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PMID:Hyaluronic acid synthesis operon (has) expression in group A streptococci. 762 71

Hyaluronan (HA) is synthesized by three HA synthases (HAS1, HAS2, and HAS3) and secreted in the extracellular matrix. In human skin, large amounts of HA are found in the dermis. HA is also synthesized by keratinocytes in the epidermis, although its epidermal functions are not clearly identified yet. To investigate HA functions, we studied the effects of HA depletion on human keratinocyte physiology within in vitro reconstructed human epidermis. Inhibition of HA synthesis with 4-methylumbelliferone (4MU) did not modify the expression profile of the epidermal differentiation markers involucrin, keratin 10, and filaggrin during tissue reconstruction. In contrast, when keratinocytes were incubated with 4MU, cell proliferation was decreased. In an attempt to rescue the proliferation function, HA samples of various mean molecular masses were added to keratinocyte cultures treated with 4MU. These samples were unable to rescue the initial proliferation rate. Furthermore, treatments with HA-specific hyaluronidase, although removing almost all HA from keratinocyte cultures, did not alter the differentiation or proliferation processes. The differences between 4MU and hyaluronidase effects did not result from differences in intracellular HA, sulfated glycosaminoglycan concentration, apoptosis, or levels of HA receptors, all of which remained unchanged. Similarly, knockdown of UDP-glucose 6-dehydrogenase (UGDH) using lentiviral shRNA effectively decreased HA production but did not affect proliferation rate. Overall, these data suggest that HA levels in the human epidermis are not directly correlated with keratinocyte proliferation and differentiation and that incubation of cells with 4MU cannot equate with HA removal.
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PMID:Hyaluronan Does Not Regulate Human Epidermal Keratinocyte Proliferation and Differentiation. 2662 28