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; DOI:10.1080/07391102.2013.790848 · 2.98 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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    • "These proteins were also identified in SH–eGFP control samples (Supplementary Table II) and include a group of abundant carboxylases (e.g. MCCC1, PCCA, ACACA) that are known to be biotinylated in vivo (Gravel and Narang, 2005), and hence most likely interact with the streptavidin column independent of the bait protein. (ii) A group of proteins including HSP70 chaperones (HSPA5, HSPA6 and HSPA8) that remained in the sample even after the second purification step (Figure 3B, orange lines). "
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    ABSTRACT: Protein complexes represent major functional units for the execution of biological processes. Systematic affinity purification coupled with mass spectrometry (AP-MS) yielded a wealth of information on the compendium of protein complexes expressed in Saccharomyces cerevisiae. However, global AP-MS analysis of human protein complexes is hampered by the low throughput, sensitivity and data robustness of existing procedures, which limit its application for systems biology research. Here, we address these limitations by a novel integrated method, which we applied and benchmarked for the human protein phosphatase 2A system. We identified a total of 197 protein interactions with high reproducibility, showing the coexistence of distinct classes of phosphatase complexes that are linked to proteins implicated in mitosis, cell signalling, DNA damage control and more. These results show that the presented analytical process will substantially advance throughput and reproducibility in future systematic AP-MS studies on human protein complexes.
    Molecular Systems Biology 02/2009; 5:237. DOI:10.1038/msb.2008.75 · 14.10 Impact Factor
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