CIDeRplusGeneral Information:
| Id: | 7,559 |
| Diseases: |
Metabolic
Phenylketonuria - [OMIM] |
| Mammalia | |
| review | |
| Reference: | Schuck PF et al.(2015) Phenylketonuria Pathophysiology: on the Role of Metabolic Alterations Aging Dis 6: 390-399 [PMID: 26425393] |
Interaction Information:
| Comment | Phe is an essential amino acid obtained exclusively by the diet or by proteolysis. Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74810 |
gene/protein decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for PAH |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74811 |
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| Drugbank entries | Show/Hide entries for PAH |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74812 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74813 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74814 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74820 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74821 |
gene/protein Phenylalanine (histidine) transaminase increases_quantity of drug/chemical compound |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74822 |
gene/protein Phenylalanine (histidine) transaminase increases_quantity of drug/chemical compound |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74823 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74824 |
gene/protein Phenylalanine (histidine) transaminase decreases_quantity of drug/chemical compound |
| Comment | Phenylalanine is hydroxylated to tyrosine by PAH, found in liver and kidney. Alternatively phenylalanine is converted to phenylpyruvic acid (PPA), which is catalyzed by the enzyme phenylalanine (histidine) transaminase (EC 2.6.1.58), found mainly in liver. This reaction is activated by the substrate phenylalanine and might therefore become more relevant if phenylalanine levels are high. The third pathway is the decarboxylation of phenylalanine to phenylethylamine by phenylalanine decarboxylase (EC 4.1.1.53). |
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Formal Description Interaction-ID: 74825 |
gene/protein Phenylalanine (histidine) transaminase decreases_quantity of drug/chemical compound |
| Comment | Phenylketonuria is an autosomal recessive disease characterized by high levels of phenylalanine due to total or partial deficiency of the enzyme PAH. |
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Formal Description Interaction-ID: 74844 |
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| Drugbank entries | Show/Hide entries for PAH |
| Comment | Phenylketonuria is an autosomal recessive disease characterized by high levels of phenylalanine and low levels of tyrosine due to total or partial deficiency of the enzyme PAH. |
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Formal Description Interaction-ID: 74845 |
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| Comment | Phenylketonuria is an autosomal recessive disease characterized by high levels of phenylalanine and low levels of tyrosine due to total or partial deficiency of the enzyme PAH. |
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Formal Description Interaction-ID: 74846 |
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| Comment | Phenylketonuria as well as hyperphenylalaninemia in animal models are both associated with increased oxidative stress (DNA, protein, lipid damage, dcecreased antioxidative defenses). |
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Formal Description Interaction-ID: 74847 |
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| Comment | Phenylpyruvate is converted to phenyllactate and phenylacetate. Both metabolites are found in the plasma of PKU patients. |
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Formal Description Interaction-ID: 74850 |
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| Comment | Phenylpyruvate is converted to phenyllactate and phenylacetate. Both metabolites are found in the plasma of PKU patients. |
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Formal Description Interaction-ID: 74851 |
drug/chemical compound increases_quantity of drug/chemical compound |
| Comment | Phenylpyruvate is converted to phenyllactate and phenylacetate. Both metabolites are found in the plasma of PKU patients. |
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Formal Description Interaction-ID: 74852 |
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| Comment | Phenylpyruvate is converted to phenyllactate and phenylacetate. Both metabolites are found in the plasma of PKU patients. |
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Formal Description Interaction-ID: 74853 |
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| Comment | Phenyllactate and phenylacetate accumulate in patients with PKU. Both metabolites increase SOD activity in rat brain tissue. |
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Formal Description Interaction-ID: 74854 |
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| Comment | Phenyllactate and phenylacetate accumulate in patients with PKU. Both metabolites increase SOD activity in rat brain tissue. |
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Formal Description Interaction-ID: 74855 |
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| Comment | Phenylpyruvate accumulates in patients with PKU. It decreases the activity of glucose-6-phosphate deydrogenase in rat brain tissue. This might explain why phenylalanine leads to oxidative stress in PKU patients. |
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Formal Description Interaction-ID: 74856 |
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| Drugbank entries | Show/Hide entries for G6PD |
| Comment | Phenylpyruvate accumulates in patients with PKU. It decreases the activity of glucose-6-phosphate deydrogenase in rat brain tissue. This might explain why phenylalanine leads to oxidative stress in PKU patients. |
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Formal Description Interaction-ID: 74857 |
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| Comment | High phenylalanine concentration in PKU patients is associated with decreased serotonin, dopamine and norepinephrine levels. |
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Formal Description Interaction-ID: 74861 |
disease decreases_quantity of drug/chemical compound |
| Drugbank entries | Show/Hide entries for |
| Comment | High phenylalanine concentration in PKU patients is associated with decreased serotonin, dopamine and norepinephrine levels. |
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Formal Description Interaction-ID: 74864 |
disease decreases_quantity of drug/chemical compound |
| Comment | Phenylalanine is a competitive inhibitor of Tyr hydroxylase and Trp hydroxylase. |
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Formal Description Interaction-ID: 74865 |
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| Comment | Phenylalanine is a competitive inhibitor of Tyr hydroxylase and Trp hydroxylase. |
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Formal Description Interaction-ID: 74866 |
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| Drugbank entries | Show/Hide entries for TH |
| Comment | Phenylalanine metabolites inhibit the enzyme dopa decarboxylase. |
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Formal Description Interaction-ID: 74867 |
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| Drugbank entries | Show/Hide entries for DDC |
| Comment | Lipid metabolism is impaired in PKU patients, which might be the reason for the hypomyelination found in PKU patients. |
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Formal Description Interaction-ID: 74868 |
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| Comment | Phe, phenylpyruvic acid and phenylacetic acid inhibit the activities of diphosphomevalonate decarboxylase (MVD) and HMGCR in an in vitro assay with chicken liver. |
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Formal Description Interaction-ID: 74869 |
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| Comment | Phenylketonuria as well as hyperphenylalaninemia in animal models are both associated with increased oxidative stress (DNA, protein, lipid damage, dcecreased antioxidative defenses). |
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Formal Description Interaction-ID: 74874 |
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| Comment | Phe, phenylpyruvic acid and phenylacetic acid inhibit the activities of diphosphomevalonate decarboxylase (MVD) and HMGCR in an in vitro assay with chicken liver. |
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Formal Description Interaction-ID: 74887 |
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| Comment | Phe, phenylpyruvic acid and phenylacetic acid inhibit the activities of diphosphomevalonate decarboxylase (MVD) and HMGCR in an in vitro assay with chicken liver. |
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Formal Description Interaction-ID: 74888 |
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| Comment | Phe, phenylpyruvic acid and phenylacetic acid inhibit the activities of diphosphomevalonate decarboxylase (MVD) and HMGCR in an in vitro assay with chicken liver. |
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Formal Description Interaction-ID: 74890 |
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| Drugbank entries | Show/Hide entries for HMGCR |
| Comment | Phe, phenylpyruvic acid and phenylacetic acid inhibit the activities of diphosphomevalonate decarboxylase (MVD) and HMGCR in an in vitro assay with chicken liver. |
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Formal Description Interaction-ID: 74891 |
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| Drugbank entries | Show/Hide entries for HMGCR |
| Comment | Phe, phenylpyruvic acid and phenylacetic acid inhibit the activities of diphosphomevalonate decarboxylase (MVD) and HMGCR in an in vitro assay with chicken liver. |
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Formal Description Interaction-ID: 74892 |
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| Drugbank entries | Show/Hide entries for HMGCR |
| Comment | Diphosphomevalonate decarboxylase (MVD) is involved in the cholesterol biosynthetic process. |
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Formal Description Interaction-ID: 74894 |
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| Drugbank entries | Show/Hide entries for |
| Comment | The level of docosahexaenoic acid, an essentail omega-3 long chain PUFA is lower in blood samples from PKU patients. |
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Formal Description Interaction-ID: 74895 |
disease decreases_quantity of drug/chemical compound |
| Comment | PKU patients present with lower levels of eicosapentaenoic acid and arachidonic acid, as compared with healthy controls. |
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Formal Description Interaction-ID: 74896 |
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| Comment | PKU patients present with lower levels of eicosapentaenoic acid and arachidonic acid, as compared with healthy controls. |
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Formal Description Interaction-ID: 74897 |
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| Drugbank entries | Show/Hide entries for |
| Comment | The catabolic products of excess phenylalanine, phenylpyruvate and phenyllactate, are proposed to inhibit synthesis of docosahexaenoic acid and arachidonic acid. |
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Formal Description Interaction-ID: 74898 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Comment | The catabolic products of excess phenylalanine, phenylpyruvate and phenyllactate, are proposed to inhibit synthesis of docosahexaenoic acid and arachidonic acid. |
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Formal Description Interaction-ID: 74899 |
drug/chemical compound decreases_quantity of drug/chemical compound |
| Comment | The catabolic products of excess phenylalanine, phenylpyruvate and phenyllactate, are proposed to inhibit synthesis of docosahexaenoic acid and arachidonic acid. |
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Formal Description Interaction-ID: 74900 |
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| Drugbank entries | Show/Hide entries for |
| Comment | The catabolic products of excess phenylalanine, phenylpyruvate and phenyllactate, are proposed to inhibit synthesis of docosahexaenoic acid and arachidonic acid. |
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Formal Description Interaction-ID: 74901 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Decreased serum coenzym Q concentrations are observed in patients with PKU. |
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Formal Description Interaction-ID: 74902 |
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| Comment | In rats subjected to high Phe concentrations the activity of creatine kinase (essential for maintenance of ATP homeostasis) is low in cerebral cortex. |
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Formal Description Interaction-ID: 74903 |
drug/chemical compound decreases_activity of gene/protein Creatine kinase |
| Comment | In rats subjected to high Phe concentrations the activity of creatine kinase (essential for maintenance of ATP homeostasis) is low in cerebral cortex. |
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Formal Description Interaction-ID: 74904 |
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| Comment | Parathyroid hormone (PTH), a hormone that regulates calcium metabolism, osteocalcin, and dehydrocholecalciferol are increased in serum samples from phenylketonuric infants, whereas calcitonin is reduced. These alterations were not reverted by Phe-restricted diet. |
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Formal Description Interaction-ID: 74910 |
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| Drugbank entries | Show/Hide entries for PTH |
| Comment | Parathyroid hormone, a hormone that regulates calcium metabolism, osteocalcin (BGLAP), and dehydrocholecalciferol are increased in serum samples from phenylketonuric infants, whereas calcitonin is reduced. These alterations were not reverted by Phe-restricted diet. |
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Formal Description Interaction-ID: 74944 |
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| Drugbank entries | Show/Hide entries for BGLAP |
| Comment | Parathyroid hormone, a hormone that regulates calcium metabolism, osteocalcin (BGLAP), and dehydrocholecalciferol are increased in serum samples from phenylketonuric infants, whereas calcitonin is reduced. These alterations were not reverted by Phe-restricted diet. |
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Formal Description Interaction-ID: 74947 |
disease increases_quantity of drug/chemical compound Dehydrocholecalciferol |
| Comment | Parathyroid hormone (PTH), a hormone that regulates calcium metabolism, osteocalcin, and dehydrocholecalciferol are increased in serum samples from phenylketonuric infants, whereas calcitonin is reduced. These alterations were not reverted by Phe-restricted diet. |
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Formal Description Interaction-ID: 74951 |
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| Drugbank entries | Show/Hide entries for PTH |
| Comment | Parathyroid hormone, a hormone that regulates calcium metabolism, osteocalcin (BGLAP), and dehydrocholecalciferol are increased in serum samples from phenylketonuric infants, whereas calcitonin is reduced. These alterations were not reverted by Phe-restricted diet. |
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Formal Description Interaction-ID: 74956 |
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| Comment | Parathyroid hormone (PTH), a hormone that regulates calcium metabolism, osteocalcin, and dehydrocholecalciferol are increased in serum samples from phenylketonuric infants, whereas calcitonin is reduced. These alterations were not reverted by Phe-restricted diet. |
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Formal Description Interaction-ID: 74957 |
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| Comment | L-carnitine and selenium supplementation reduces oxidative stress in patients with Phenylketonuria. |
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Formal Description Interaction-ID: 75887 |
drug/chemical compound decreases_activity of process |
| Comment | L-carnitine and selenium supplementation reduces oxidative stress in patients with Phenylketonuria. |
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Formal Description Interaction-ID: 75888 |
drug/chemical compound decreases_activity of process |
| Comment | Animals fed with Phe-rich diet present with lower serotonin levels and impaired behavior. |
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Formal Description Interaction-ID: 75889 |
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| Comment | Patients with Phenylketonuria have lower levels of total cholesterol, HDL, LDL and apolipoprotein A-I/A-II and B. |
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Formal Description Interaction-ID: 75890 |
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| Drugbank entries | Show/Hide entries for |
| Comment | Patients with Phenylketonuria have lower levels of total cholesterol, HDL, LDL and apolipoprotein A-I/A-II and B. |
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Formal Description Interaction-ID: 75891 |
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| Comment | Patients with Phenylketonuria have lower levels of total cholesterol, HDL, LDL and apolipoprotein A-I/A-II and B. |
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Formal Description Interaction-ID: 75892 |
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| Comment | Patients with Phenylketonuria have lower levels of total cholesterol, HDL, LDL and apolipoprotein A-I/A-II and B. |
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Formal Description Interaction-ID: 75893 |
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| Comment | Patients with Phenylketonuria have lower levels of total cholesterol, HDL, LDL and apolipoprotein A-I/A-II and B. |
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Formal Description Interaction-ID: 75894 |
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| Comment | Patients with Phenylketonuria have lower levels of total cholesterol, HDL, LDL and apolipoprotein A-I/A-II and B. |
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Formal Description Interaction-ID: 75895 |
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| Comment | In a murine model for PKU the rate-controlling enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), is down-regulated. |
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Formal Description Interaction-ID: 75896 |
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| Drugbank entries | Show/Hide entries for HMGCR |
| Comment | In a murine model for PKU the rate-controlling enzyme, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), is down-regulated. |
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Formal Description Interaction-ID: 75897 |
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| Drugbank entries | Show/Hide entries for HMGCR |
| Comment | Levels of oxysterols and vitamin D, which are metabolites from cholesterol, are decreased in serum from phenylketonuric adult patients. |
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Formal Description Interaction-ID: 76054 |
disease decreases_quantity of drug/chemical compound Vitamin D |
| Comment | Addition of phenylpyruvic acid (PPA) and phenylalanine inhibits pyruvate kinase. |
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Formal Description Interaction-ID: 76065 |
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| Comment | Addition of phenylpyruvic acid (PPA) and phenylalanine inhibits pyruvate kinase. |
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Formal Description Interaction-ID: 76066 |
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