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Molecular genetics of biotin metabolism: Old vitamin, new science

Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
The Journal of Nutritional Biochemistry (Impact Factor: 4.59). 08/2005; 16(7):428-31. DOI: 10.1016/j.jnutbio.2005.03.020
Source: PubMed

ABSTRACT Biotin is a water-soluble vitamin that participates as a cofactor in gluconeogenesis, fatty acid synthesis and branched chain amino acid catabolism. It functions as the carboxyl carrier for biotin-dependent carboxylases. Its covalent attachment to carboxylases is catalyzed by holocarboxylase synthetase. Our interest in biotin has been through the genetic disease, "biotin-responsive multiple carboxylase deficiency," caused by deficient activity of holocarboxylase synthetase. As part of these studies, we made the unexpected findings that the enzyme also targets to the nucleus and that it catalyzes the attachment of biotin to histones. We found that patients with holocarboxylase synthetase deficiency have a much reduced level of biotinylated histones, yet the importance of this process is unknown. The dual nature of biotin, as the carboxyl-carrier cofactor of carboxylases and as a ligand of unknown function attached to histones, is an enigma that suggests a much more involved role for biotin than anticipated. It may change our outlook on the optimal nutritional intake of biotin and its importance in biological processes such as development, cellular homeostasis and regulation.

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    • "Biotin, also called vitamin H or B7, composed of ureido and tetrahydrothiophene rings sideways fused and by a valeryl chain, plays a key role in many metabolic reactions (Gravel & Narang, 2005; Pacheco-Alvarez, Solorzano- Vargas, & Del Rio, 2002). Biotin is also largely known for its high affinity (k a ≈ 10 13 M À1 ) (Green, 1975) with the tetrameric protein streptavidin (Weber, Ohlendorf, Wendoloski , & Salemme, 1989) and, because of such feature, is largely used in biochemistry, immunology and biotechnology . "
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    ABSTRACT: Despite the increasing use and development of peptide-based scaffolds in different fields including that of regenerative medicine, the understanding of the factors governing the self-assembly process and the relationship between sequence and properties have not yet been fully understood. BMHP1-derived self-assembling peptides (SAPs) have been developed and characterized showing that biotinylation at the N-terminal cap corresponds to better performing assembly and scaffold biomechanics. In this study, the effects of biotinylation on the self-assembly dynamics of seven BMHP1-derived SAPs have been investigated by molecular dynamics simulations. We confirmed that these SAPs self-assemble into β-structures and that proline acts as a β-breaker of the assembled aggregates. In biotinylated peptides, the formation of ordered β-structured aggregates is triggered by both the establishment of a dense and dynamic H-bonds network and the formation of a 'hydrophobic wall' available to interact with other peptides. Such conditions result from the peculiar chemical composition of the biotinyl-cap, given by the synergic cooperation of the uracil function of the ureido ring with the high hydrophobic portion consisting of the thiophenyl ring and valeryl chain. The inbuilt propensity of biotinylated peptides towards the formation of ordered small aggregates makes them ideal precursors of higher hierarchically organized self-assembled nanostructures as experimentally observed.
    Journal of biomolecular Structure & Dynamics 06/2013; 32(5). DOI:10.1080/07391102.2013.790848 · 2.98 Impact Factor
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    • "Phosphopantetheinylation and biotinylation are two posttranslational modifications, which occur widely in living organisms, especially in metabolic enzymes to regulate their activity, such as aromatic carboxylic acid reductase, non-ribosomal peptide synthetases (NRPSs), polyketide synthases (PKSs) and carboxylases [16], [17], [18]. Biotinylation of histone H4 has been recently found to be involved in the regulation of nucleosome structure and gene transcription [19]. "
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    ABSTRACT: The correct folding of a protein is a pre-requirement for its proper posttranslational modification. The Escherichia coli Sec pathway, in which preproteins, in an unfolded, translocation-competent state, are rapidly secreted across the cytoplasmic membrane, is commonly assumed to be unfavorable for their modification in the cytosol. Whether posttranslationally modified recombinant preproteins can be efficiently transported via the Sec pathway, however, remains unclear. ACP and BCCP domain (BCCP87) are carrier proteins that can be converted into active phosphopantetheinylated ACP (holo-ACP) and biotinylated-BCCP (holo-BCCP) by AcpS and BirA, respectively. In the present study, we show that, when ACP or BCCP87 is fused to the C-terminus of secretory protein YebF or MBP, the resulting fusion protein preYebF-ACP, preYebF-BCCP87, preMBP-ACP or preMBP-BCCP87 can be modified and then secreted. Our data demonstrate that posttranslational modification of preYebF-ACP, preYebF-BCCP87 preMBP-ACP and preMBP-BCCP87 can take place in the cytosol prior to translocation, and the Sec machinery accommodates these previously modified fusion proteins. High levels of active holo-ACP and holo-BCCP87 are achieved when AcpS or BirA is co-expressed, especially when sodium azide is used to retard their translocation across the inner membrane. Our results also provide an alternative to achieve a high level of modified recombinant proteins expressed extracellularly.
    PLoS ONE 08/2012; 7(8):e42519. DOI:10.1371/journal.pone.0042519 · 3.23 Impact Factor
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    • "It is our theory that low serum biotin levels initiate a series of biochemical events that leads potentially to the release of harmful lipid peroxidation by-products. In recent literature, it was found that biotin plays an important role in the regulation of chromatin structures, gene expression, and DNA repair (Gravel and Narang, 2005; Hassan and Zempleni, 2006). In this study, there was a strong correlation between low biotin serum levels and oxidant by-products suggesting a role for biotin in its libration or as an antioxidant. "
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    ABSTRACT: Serum biotin concentrations, erythrocyte superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), reduced glutathione (GSH) and plasma thiobarbituric acid reactive substances (TBARS) were measured in 36 dairy cows, 18 of them were healthy and served as control. In the 18 cows with lameness problems, there were 5 cows with interdigital necrobacillosis, 5 cows with subsolar abscessation, 2 cows with solar ulcers, 2 cows with white line disease, 2 cows with chronic laminitis and 2 cows with septic arthritis. The degree of lameness was estimated to be slight in 3 cows, moderate in 11 cows and severe in 4 cows. Plasma fibrinogen levels and TBARS concentrations were increased significantly (P≤0.05) in lame cows compared to control group. The antioxidant enzymes GSH-Px, and CAT concentrations were increased significantly (P≤0.05) in lame cows. The level of reduced glutathione and the activity of SOD were significantly decreased in affected cows compared to healthy ones. Serum biotin levels in healthy cows ranged from 2.25 to 3.5ng/ml while in lame cows, biotin levels ranged from 1.17 to 2.3ng/ml. Biotin levels correlated positively with blood GSH (r=0.870, P≤0.05), (r=0.735, P≤0.05) and with GSH-Px (r=0.539, P≤0.05), (r=0.637, P≤0.05) and with SOD (r=0.637, P≤0.05), (r=0.449, P≤0.05) and with catalase (r=0.533, P≤0.05), (r=0.585, P≤0.05) in both healthy and lameness affected subjects, respectively.
    Research in Veterinary Science 11/2010; 92(1):138-41. DOI:10.1016/j.rvsc.2010.10.017 · 1.51 Impact Factor
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