Inhibition of Intestinal Biotin Absorption by Chronic Alcohol Feeding:Cellular and Molecular Mechanisms
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1. Yeast cells grown in the presence of an unknown radioactive biotin vitamer produced by Penicillium chrysogenum incorporated the vitamer into the newly synthesized biotin. 2. The biotin was isolated as the avidin-biotin complex and after hydrolysis the biological activity and radioactivity were shown to be coincidental. 3. The specific activity of the biotin was identical with that of the pimelic acid used in a previous investigation to label the unknown vitamer. 4. The role of the unknown biotin vitamer as an intermediate in biotin biosynthesis is discussed.
Avidin
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Avidin
Biotin deficiency
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Biotin is a water soluble enzyme cofactor that belongs to the vitamin B complex. In humans, biotin is involved in important metabolic pathways such as gluconeogenesis, fatty acid synthesis, and amino acid catabolism by acting a as prosthetic group for pyruvate carboxylase, propionyl-CoA carboxylase, beta-methylcrotinyl-CoA carboxylase, and acetyl-CoA carboxylase. Carboxylases are synthesized as apo-carboxylases without biotin and the active form is produced by their covalent binding of biotin to the epsilon-amino group of a lysine residue of the apocarboxylases. This reaction is catalyzed by the holo-carboxylase synthetase. The last step in the degradation of carboxylases, the cleavage of the biotinyl moiety from the epsilon-amino group lysine residues, is catalyzed by biotinidase and results in the release of free biotin, which can be recycled. Biotin regulates the catabolic enzyme propionyl-CoA carboxylase at the posttranscriptional level whereas the holo-carboxylase synthetase is regulated at the transcriptional level. Aside from its role in the regulation of gene expression of carboxylases, biotin has been implicated in the induction of the receptor for the asialoglycoprotein, glycolytic enzymes and of egg yolk biotin binding proteins. Biotin deficiency in humans is extremely rare and is generally associated with prolonged parenteral nutrition, the consumption of large quantities of avidin, usually in the form of raw eggs, severe malnutrition and, inherited metabolic disorders. In humans, there are autosomal recessive disorders of biotin metabolism that result from the disruption of the activity of biotinidase or holo-carboxylase synthetase.
Biotin deficiency
Acetyl-CoA Carboxylase
Fatty acid synthesis
Avidin
Catabolism
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In common with other organisms which require biotin for growth, L. easei can utilize the methyl ester of biotin. However growth and fermentation are slower than with free biotin.
Lactobacillus casei
Vitamin b complex
Biotin deficiency
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After a short account of the discovery of biotin and the progress of early biotin research, the natural occurrence of biotin with particular consideration to the raw materials used in the fermentation industry and its products is described. Of the many known biotin derivatives, those appearing in nature and those which can be converted to biotin-active (or inactive) compounds by simple procedures are reported. Ways to by-pass the need for biotin in microbes is discussed. The importance of biotin in yeast production, the biotin requirements of yeast, and the effect of culture conditions on these requirements are reported. The close relationship between the participation of biotinylenzymes and the biotin requirements is noted.
Biotin deficiency
Vitamin b complex
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Biotin deficiency
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Avidin
Streptavidin
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Streptavidin
Biotin deficiency
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The endosomal entrapment of functional nanoparticles is a severe limitation to their use for biomedical applications. In the case of magnetic nanoparticles (MNPs), this entrapment leads to poor heating efficiency for magnetic hyperthermia and suppresses the possibility to manipulate them in the cytosol. Current strategies to limit their entrapment are based on their functionalization with cell-penetrating peptides in order to promote their translocation directly across the cell membrane or their endosomal escape. However, these strategies suffer from potential release of free peptides in cell and to the best of our knowledge there is currently a lack of effective methods for the cytosolic delivery of MNPs after incubation with cells. Herein, we report the conjugation of fluorescently labelled cationic peptides to γ-Fe2O3@SiO2 core-shell nanoparticles by click chemistry to improve MNP access to the cytosol. We compare the effect of Arg9 and His4 peptides. On one hand, Arg9 is a classical cell-penetrating peptide, able to enter cells by direct translocation and on the other hand, it has been demonstrated that sequences rich in histidine residues promote endosomal escape, most probably by the proton sponge effect. The methodology developed allows to have a high co-localization of the peptides and core-shell nanoparticles in cells and to attest that the grafting onto nanoparticles of peptides rich in histidine promotes NP access to the cytosol. The endosomal escape was confirmed by a calcein leakage assay and by ultrastructural analysis in transmission electron microscopy. No toxicity of the nanoparticles functionalized with peptides was found. We show that our conjugation strategy is compatible with the addition of multiple substrates and can thus be used for the delivery of cytoplasm-targeted therapeutics.
Cell-penetrating peptide
Calcein
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d-Biotin, dl-desthiobiotin, 7, 8-diaminopelargonic acid, 7-keto, 8-aminopelargonic acid, 7-amino, 8-keto-pelargonic acid, 7, 8-diketopelargonic acid並びにoleic acidを単一のgrowth factorとする培地でbiotin要求性のあるBrevibacterium lactofermentum No. 2256を用いL-グルタミン酸醗酵を行なわしめ,その醗酵菌体中のbiotinを調べた.菌体の硫酸加水分解液につきビオアッセイ法を適用し, biotinの存在することを認めた.特にd-biotin以外のgrowth factor醗酵菌体中にもd-biotinの場合と同様に著量のbiotinが検出された.ビオアッセイ-biotinはbioautographによりおおむねd-biotinに一致すると確認された.この結果から本細菌は前記6種growth factor物質よりd-biotinを生合成する能力のあることが判る.またこれら6種growth factorよりのd-biotin生成率の大小順列が先に提示したbiotin生合成系路上の配列順序と一致し, d-biotinをに近いものほどbiotin生成率が高く,遠いものほど低かった.この関係は生合成系路上にある諸前駆体の配列の正しいことの一証拠と考えられた.従って本菌のbiotin生合成系路はpimelic acid→7, 8-diketopelargonic acidの間では完全に欠除しているように思われる.
Biotin deficiency
Glutamic acid
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