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G Formiggini

Publications and source records attributed to G Formiggini.

At least 37 records · Page 2Linked to original sources

Liver cytosolic protein-bound folates in phenobarbitone-treated rats.

The effect of acute phenobarbitone treatment on the distribution of endogenous bound folates in three specific cytosolic folate-binding proteins (FBP-C), has been studied in rat liver. The bound folate amount shows no difference between treated and control rats. As it is well known that FBP's preferentially bind longer-chain polyglutamates, the content of which is markedly lower in phenobarbitone-treated rat liver, it might be suggested that shorter chain folates also bind to FBP's in these animals.

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Protein bound folates in liver of castrated rats.

The effect of castration and testosterone treatment on the distribution of [3H] radioactive and endogenous bound folates in hepatic cytosolic folate binding proteins (FBP-C) has been studied in rats. The distribution of [3H] radioactive bound folates in these FBP's shows no significant difference in the three experimental group animals. On the contrary a significant decrease in the amount of endogenous bound folates is observed in castrated if compared with control rats, particularly marked for FBP-CI and FBP-CII bound folates. The testosterone treatment of castrated rats partially restores bound folate levels. The decrease of bound folates in castrated rats might be ascribable to a lower availability of longer-chain forms, almost the ones that bind to FBP's; however lower binding protein content and/or lower affinity for ligands cannot be excluded.

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The time course of [3H]PteGlu uptake and its incorporation into pteroylpolyglutamates in liver of phenobarbitone treated rats.

The uptake of an injected dose of [3H]PteGlu and its incorporation into folate forms in the liver of control and phenobarbitone-treated rats were investigated at a number of time intervals from 1 to 24 h. At 1 h the hepatic uptake of the label was quite similar in both groups of animals and radioactivity was incorporated only in pteroylmonoglutamates. At 6 h label was present also in pteroylpolyglutamate forms and radioactivity values were similar in the two groups. At longer time periods the radioactivity was lower in treated animals than in control ones. The whole data show that phenobarbitone on the one hand does not modify the transport of the vitamin; on the other, it does interfere with "pteroylpolyglutamate synthetase activity".

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The uptake of [3H] pteroylglutamic acid into rat liver during regeneration and its incorporation into pteroylpolyglutamates of that organ.

The metabolism of injected [3H] PteGlu in hepatectomized rats was studied. Significantly higher radioactivity was found in all folate derivatives of regenerating liver. The results confirm the hypothesis according to which the decrease of endogenous polyglutamate content of regenerating liver might be ascribed to greater utilization rather than to lower synthesis of these coenzymes.

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Effect of phenobarbitone on folic acid metabolism in the rat.

Anticonvulsant drugs have well-known relationships with folic acid, often leading, in epileptic patients on long term treatment to signs of folic acid deficiency and to haematological complications. The findings of this work, carried out on rats, show strong interference of phenobarbitone with folic acid metabolism, particularly with pteroylpolyglutamate synthesis in liver. This is proved by lower polyglutamate content, lower 3H folate incorporation in polyglutamate forms and in protein-bound folates, and also by lower blood radioactivity, higher urinary excretion of 3H folate metabolites and by higher 3H folate concentration in kidneys.

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The metabolism of [3H] pteroylglutamic acid in rat liver during regeneration after partial hepatectomy.

The rate of [3H] PteGlu uptake and of its incorporation into pteroylpolyglutamate derivatives at different times after label administration, was studied in the regenerating liver of rats 36 hr after partial hepatectomy. While 1 hr after administration of labelled PteGlu the radioactivity levels in regenerating livers are quite similar to controls, they are markedly higher 6, 12, 24 hr after label injection, which is mostly due to the high polyglutamate content. If the regenerating process, on the one hand does not modify the folate uptake rate, it does, on the other, increase the capacity for retaining folates, thanks to a more powerful ability to convert them into pteroylpolyglutamates.

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Uptake and metabolism of [3H] pteroylglutamic acid by developing chick embryo.

Chick embryos at 9 and 12 days of development were injected into the air space with [3', 5', 7, 9 -3H]pteroylglutamic acid. After various time periods the incorporation of radioactivity into folate derivatives was measured. In the 9-day embryo the label incorporation into longer chain polyglutamates, expressed per gram, was higher than in the 12-day embryo. Since the endogenous content of these compounds was lower at 9 days, the results suggest that, at this stage of development, the turnover of longer pteroylpolyglutamates is more rapid.

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Pteroylpolyglutamates in liver of phenobarbitone-treated rats.

The effects of "acute" phenobarbitone treatment on some aspects of folate metabolism in rat liver, that is total folate activity, protein bound and free folate, and various-length pteroylpolyglutamate amounts, were studied. The administration of two doses of the anticonvulsant drug (8 mg/100 g of body weight), caused a severe depletion in folate pool, free folate and in the percentage of longer-chain polyglutamates, while the amount of protein bound folates was unchanged. Such modifications are more evident in the animals killed at 24 h after the last drug injection rather than in those killed 12 h later. The possible mechanisms by which phenobarbitone might interfere with the synthesis of pteroylpolyglutamates, the actual coenzymic forms of folic acid, are discussed.

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[Effect of folic acid deficiency on the synthesis of pteroylpolyglutamates].

In order to evaluate the effect of folate deficiency on pteroylpolyglutamate synthesis in rat liver, the hepatic and urinary content of reduced folates, the distribution of pteroylpolyglutamates and the incorporation of i.p. injected 3H folic acid in polyglutamates have been studied. In deficient rats the hepatic content of reduced folates and the urinary amounts of reduced metabolites are lower and do not increase after vitamin treatment. Longer chain pteroylpolyglutamates are severely depleted and their content is not significantly modified by folic acid treatment. The percentage of labelled folic acid incorporated into pteroylglutamates is markedly decreased. The inability of deficient rat liver to synthesize polyglutamates might be ascribed to the decrease of pteroylpolyglutamate synthetase activity, and/or to the lower availability of tetrahydrofolates, the preferred substrates for the enzyme.

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[Folic acid metabolism in rapidly growing tissues: synthesis of pteroylpolyglutamates].

Pteroylpolyglutamates are regarded as the functional coenzyme form of folate: hence their synthesis may represent important regulatory step in the folate-dependent processes. To verify this hypothesis the pteroylpolyglutamate content was studied in rapidly growing tissues, which require a large availability of folate coenzymes, essential as carbon atom donors in the synthesis of purine and pyrimidine nucleotides and in the metabolism of some aminoacids. In the developing chick embryo, the higher polyglutamates are the only folate forms present and their content increases progressively during the development of the embryo. In rat liver regenerating after partial hepatectomy the higher polyglutamate forms decrease below the normal values from 12 to 72 h after the operation; the normal values are restored after 180 h. The initial drop is not related to a lower synthesis, but to a greater utilization of these coenzymes during the early periods of regeneration, when biosynthetic processes are markedly increased. In fact the content of polyglutamates in regenerating liver can be maintained at normal levels by increasing the availability of precursors via folic acid administration to hepatectomized rats.

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Distribution of pteroylglutamates in rat liver during regeneration after partial hepatectomy.

1. Liver pteroylpolyglutamate distribution was studied during regeneration after partial hepatectomy in rats maintained under controlled feeding conditions. 2. Pteroylhexaglutamate, pteroylpentaglutamate and pteroyltetraglutamate concentrations decrease from 12 to 72 h after operation, then increase and reach normal values at 180 h. Pteroyltriglutamate concentration, already high at 12 h, remains so in the subsequent periods. Pteroyldiglutamate concentration was unchanged. Monoglutamate concentrations at first decrease, and at 180 h exceed normal values. 3. The decrease in polyglutamate derivatives with a high number of glutamate residues, at present considered to be the coenzyme forms of folate, could be related not to a decreased synthesis, but to a greater requirement for these compounds during the early periods of regeneration, when biosynthetic processes are markedly increased. It is indeed probable that the increased availability of the preferred substrate of pteroylpolyglutamate synthetase, i.e. tetrahydrofolate, enhances conversion of folate into coenzyme forms.

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Synthesis of pteroylpolyglutamates in rat liver during regeneration after partial hepatectomy.

The liver content of higher polyglutamate forms of folic acid, which in partially hepatectomized rats is markedly lower as compared with sham operated animals, is normalized by the vitamin administration. The greater availability of folic acid and consequently of the tetrahydrofolates, promotes the synthesis of actual coenzymic forms; so their content, in regenerating liver, is maintained at normal values in spite of a higher requirement caused by the exaltation of biosynthetic processes.

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Polyglutamate forms of folate in liver of folic acid-deficient rats.

In view of role played by pteroylpolyglutamates as actual folate coenzymes in single-carbon unit metabolism, the effect of folic acid deficiency on the distribution of these compounds in rat liver has been studied. In deficient rats the liver levels of pteroylpolyglutamates and in particular of those containing a higher number of glutamyl residues are more decreased as compared with monoglutamates. In fact penta- and other higher polyglutamates: mono-, di- and tri-glutamates ratio is lower in deficient rats than that in control rats. The decreased amount of these coenzymic forms observed in this condition may be considered as the consequence of the severe alterations of process which adds glutamate moieties to monoglutamate forms.

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Studies on folate metabolism in folic acid-deficient rats.

The distribution in liver of pteroylpolyglutamates and urinary excretion of folate metabolites was studied in folic acid deficient rats after injection of the vitamin, in order to evaluate the effect of folic acid deficiency on the conversion of the vitamin into actual coenzymic forms. Any significant difference neither in total activity nor in pteroylpolyglutamates of liver does not appear between deficient supplemented and unsupplemented animals. Also the urinary amounts of reduced metabolites in deficient rats do not increase after injection of folic acid. Therefore the inability of deficient rat liver to synthesize polyglutamates may be ascribed to the lower availability of tetrahydrofolates as they are the preferred substrates of pteroylpolyglutamate synthetase.

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