Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.11.2 (prolyl hydroxylase)
 1,814 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Binding of iron with the molecule of prolyl hydroxylase was studied using 59Fe. The label was administered into one-day-old rats and within 36 hours the enzyme was isolated from skin. After the final step of purification (DEAE cellulose) 59Fe was not found in fractions of prolyl hydroxylase. The purity of the enzyme preparations was controlled by polyacrylamide gel disc electrophoresis. The data obtained suggest that Fe ions are not inherent in the enzyme molecule.
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PMID:[Presence of iron in the composition of prolyl hydroxylase]. 19 81

We studied 12 members of a family with precirrhotic hemochromatosis to define the physiologic abnormalities in the asymptomatic phase of the disease. Six of 12 had increased iron stores; the mode of inheritance was consistent with an autosomal dominant trait. Serum ferritin levels were no more predictive of tissue iron levels than measurements of serum iron, transferrin saturation or chelatable iron excretion. In three affected family members intestinal iron content was normal. Liver proline hydroxylase activity and urinary hydroxyproline excretion did not correlate with tissue iron content, suggesting that, in addition to the possible role of tissue iron, hepatic fibrosis may involve other factors. "Borderline diabetes mellitus" was present in three affected family members, but extensive studies revealed that pituitary dysfunction is uncommon in early hemochromatosis. Increased levels of liver iron proved to be the most reliable marker for the disease.
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PMID:Familial hemochromatosis. Physiologic studies in the precirrhotic stage of the disease. 19 51

The activity of procollagen prolyl hydroxylase was measured in fibrotic liver obtained from mice with hepatosplenic schistosomiasis, an animal model of the most prevalent form of human liver fibrosis. Measurable activity of prolyl hydroxylase in fibrotic liver supernatants was 47-fold higher than that of normal liver. The effect of prolyl hydroxylase inhibition on collagen synthesis in fibrotic liver slices was studied, using 8,9-dihydroxy-7-methyl benzo[b]quinolizinium bromide (GPA 1734). This compound was shown in other systems to inhibit prolyl and lysyl hydroxylations by iron chelation at concentrations which did not affect total protein synthesis. The formation of nondialyzable labelled hydroxyproline was inhibited by GPA 1734, 40, 70 and 95% at 30, 50 and 100 micrometer, respectively. Incorporation of proline into total liver protein was unaffected at 30 and 50 micrometer, but was inhibited 20% at 100 micrometer GPA 1734. Underhydroxylated collagen synthesized by liver slices with GPA 1734 was extracted with neutral salt solution and was subsequently hydroxylated with partially-purified prolyl hydroxylase to the same extent as control material synthesized in the absence of GPA 1734.
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PMID:Liver collagen hydroxylation in murine schistosomiasis. 20 35

Rats of Wistar strain, of same age, were kept on iron free diet up to nearly absolute iron deficiency in iron depots. Afterwards granuloma was produced by implantation of cotton pellets subcutaneously. For characterization of the collagen biosynthesis in the granuloma the neutral salt soluble collagen and the activity of the prolyl hydroxylase were measured in the granuloma 4, 8 and 12 days after cotton pellet implantation. At the same time "collagen-like" protein was determined in the serum of the animals. The enzyme activity was statistically significant lower in the granuloma of animals on iron deficiency than in the granuloma of the comparable groups on normal diet. Statistically significant higher concentration of neutral salt soluble collagen was found 8 and 12 days after cotton pellet implantation in the group on iron free diet. There was no significant difference as to the serum levels of "collagen-like" protein in serum.
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PMID:[Parameters of collagen biosynthesis in cotton pellet granuloma of rats on iron deficiency (author's transl)]. 21 Apr 87

The activity of collagen prolyl hydroxylase in aortic wall was studied in rabbits exposed to chronic 10% ambient oxygen tension for 30 days. Prolyl hydroxylase in rabbit aorta was shown to be similar to the enzyme from other sources in that it required molecular oxygen, alpha-ketoglutarate, ferrous iron and ascorbate for its activity. The activity of prolyl hydroxylase was increased to 180% of controls in the intima-media samples from rabbits exposed to hypoxia. No atherosclerotic lesions could be seen in arteries of animals kept in chronic hypoxia. If the arteries of rabbits were injured with a single mechanical dilatation, the activity of prolyl hydroxylase increased more than 2-fold, as reported previously. The exposure of these animals to chronic hypoxia further elevated the prolyl hydroxylase activity.
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PMID:Increased collagen prolyl hydroxylase activity in the aortic wall of rabbits exposed to chronic hypoxia. 22 78

Iron is essential for the activity of proline hydroxylase and is an important co-factor in collagen synthesis. Fibroblast cultures exposed to desferrioxamine show impairment of DNA synthesis and reduced collagen formation, as measured by hydroxyproline synthesis and the deposition of hydroxyproline in the cell mat. In patients with transfusional iron overload long-term treatment with desferrioxamine is said to result in the inhibition of hepatic fibrosis. It is suggested that this may be a direct effect on collagen synthesis rather than an effect of reduced iron stores.
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PMID:The effect of desferrioxamine on fibroblasts and collagen formation in cell cultures. 42 Jul 37

The mechanism by which tetracyclines affect the formation of dentin was studied by measuring the biosynthesis of collagen in the pulp. The material consisted of 160 rabbit pulps and 108 rat pulps. Collagen synthesis was determined by incubating pulps with [14C]proline and measuring the formation of non-dialyzable [14C]hydroxyproline. The activity of protocollagen proline hydroxylase was measured as the conversion of [14C]proline to [14C]hydroxyproline in a protocollagen substrate by the supernatant of a pulp homogenate. In in vitro experiments, oxytetracycline or demethylchlortetracycline inhibited collagen synthesis. Also, the activity of protocollagen proline hydroxylase extracted from rabbit pulps was decreased in the presence of tetracyclines. In both cases the inhibition was related to the concentration of tetracyclines and the inhibition could be prevented by addition of ferrous iron to the incubation. In in vivo studies, injections of demethylchlortetracycline to rats inhibited collagen synthesis measured in vitro and the activity of protocollagen proline hydroxylase in the incisor pulps. It was concluded that this effect may be specific to collagen synthesis and the effect may be through chelation of ferrous iron, a cofactor of protocollagen proline hydroxylase. Consequently, the mineralization disturbances in developing teeth during tetracycline therapy may be partly due to a decreased formation of the organic matrix of dentin.
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PMID:Effect of tetracyclines on collagen biosynthesis in the dental pulp. 82 92

The action of hydralazine on collagen prolyl hydroxylation was studied in a cell culture system using WI-38 fibroblasts. The prolyl hydroxylation level was determined by a method involving the digestion of collagen by bacterial collagenase and the examination of specific peptides. The presence of low concentrations of hydralazine (0.2 mM) in both "young" and "old" fibroblast cultures strongly inhibited collagen prolyl hydroxylation. The degree of inhibition was greater in serum-deficient cultures. No significant improvement in the degree of hydroxylation was observed by increasing either ascorbate or iron levels in the hydralazine-containing cultures in which hydroxylation was inhibited. Some of the reported side effects of hydralazine seen in patients might be related to its inhibitory effects on mixed function oxidative (MFO) hydroxylation systems. While the ascorbate dependence of the prolyl hydroxylase system of WI-38 decreased with the "age" of the culture, hydralazine inhibition of hydroxylation was dramatic with cultures of all "ages".
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PMID:Collagen prolyl hydroxylation in WI-38 fibroblast cultures: action of hydralazine. 85 25

Ffty asymptomatic members of a kindred with familial hemochromatosis were studied in an effort to clarify some of the physiologic abnormalities present in the pre-cirrhotic or latent stage of the disease. Using excess hepatic iron as a marker for inheritance of hemochromatosis, results of liver biopsies on 31 family members suggest an auto-somal dominant mode of inheritance with incomplete expressivity. In addition to a relationship between alcohol intake and excess liver iron, there was a strong association between the level of alcohol intake and the presence of hepatic fibrosis in those subjects with excess iron stores. Both serum iron and transferrin saturation were significantly higher in family members with iron overload than in those who were not affected. Only transferrin saturation was significantly correlated with the severity of hepatic iron deposition. Studies of glucose tolerance (OGTT, IVITT, glucose clamp studies) demonstrated a defect in carbohydrate metabolism associated with deficient insulin secretion and insulin resistance, both of which were related to the degree of hepatic iron depostion. In this kindred we have found no evidence for a contribution of inheritance to the carbohydrate intolerance of hemochromatosis. Iron overload was not related to activity of hepatic collagen proline hydroxylase or urinary excretion of peptide-bound hydroxyproline. Serum ferritin, previously thought to be a reliable marker of reticuloendothelial iron stores, was normal in 19 of 20 family members with iron overload.
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PMID:Familial hemochromatosis: characteristics of the precirrhotic stage in a large kindred. 87 Jul 91

Prolyl 4-hydroxylase, a key enzyme in collagen biosynthesis, catalyzes the conversion of selected prolyl residues to trans-hydroxyproline in nascent or completed pro-alpha chains of procollagen. The enzyme is a tetramer composed of two nonidentical subunits, designated alpha and beta. To compare the enzyme and its subunits from different sources, the chick embryo and human placental prolyl 4-hydroxylases were purified to homogeneity and their physicochemical and immunological properties were determined. Both enzymes were glycoproteins with estimated apparent molecular weights ranging between 400 and 600 kDa. Amino acid and carbohydrate analyses showed slight differences between the two holomeric enzymes, consistent with their deduced amino acid sequences from their respective cDNAs. Human placental prolyl 4-hydroxylase contained more tightly bound iron than the chick embryo enzyme. Immunodiffusion of the human placental enzyme with antibodies raised against the purified chick embryo prolyl 4-hydroxylase demonstrated partial identity, indicating different antigenic determinants in their tertiary structures. The enzymes could be separated by high-resolution capillary electrophoresis, indicating differential charge densities for the native chick embryo and human placental proteins. Electrophoretic studies revealed that the human prolyl 4-hydroxylase is a tetrameric enzyme containing two nonidentical subunits of about 64 and 62 kDa, in a ratio of approximately 1 to 2, designated alpha and beta, respectively. In contrast, the chick embryo alpha and beta subunit ratio was 1 to 1. Notably, the human alpha subunit was partially degraded when subjected to electrophoresis under denaturing conditions. Analogously, when the chick embryo enzyme was subjected to limited proteolysis, selective degradation of the alpha subunit was observed. Finally, only the alpha subunit was bound to Concanavalin A demonstrating that the alpha subunits of prolyl 4-hydroxylase in both species were glycosylated. Using biochemical techniques, these results demonstrated that the 4-trans-hydroxy-L-proline residues in human placental collagens are synthesized by an enzyme whose primary structure and immunological properties differ from those of the previously well-characterized chick embryo enzyme, consistent with their recently deduced primary structures from cDNA sequences.
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PMID:Comparison between avian and human prolyl 4-hydroxylases: studies on the holomeric enzymes and their constituent subunits. 132 42


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