Biotin in Metabolism and Its Relationship to Human Disease

Pacheco‐Alvarez, Diana; Solorzano–Vargas, R. Sergio; Río, Alfonso León del

doi:10.1016/s0188-4409(02)00399-5

Cited by 120 publications

(82 citation statements)

References 84 publications

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“…1 In Escherichia coli, the biotin carboxyl carrier protein (BCCP), a subunit of acetyl-CoA carboxylase, uses biotin as a cofactor. [2][3][4] In mammals, there are five biotin-dependent carboxylases: two distinct acetyl-CoA carboxylases, b-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase, and pyruvate carboxylase. 1 In all carboxylases, biotin is covalently attached to the e-amino group of a lysine residue within a highly conserved hydrophobic sequence, Ala/ Val-Met-Lys-Met/Leu.…”

Section: Introductionmentioning

confidence: 99%

Nonenzymatic biotinylation of histone H2A

et al. 2009

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Holocarboxylase synthetase (HCS, eukaryotic enzyme) and BirA (prokaryotic) are biotin protein ligases that catalyze the ATP-dependent attachment of biotin to apocarboxylases via the reactive intermediate, bio-5 0 -AMP. In this study, we examined the in vitro mechanism of biotin attachment to histone H2A in the presence of HCS and BirA. The experiment derives from our observations that HCS is found in the nucleus of cells in addition to the cytoplasm, and it has the ability to attach biotin to histones in vitro (Narang et al., Hum Mol Genet 2004; 13:15-23). Using recombinant HCS or BirA, the rate of biotin attachment was considerably slower with histone H2A than with the biotin binding domain of an apocarboxylase. However, on incubation of recombinant H2A with chemically synthesized bio-5 0 -AMP, H2A was observed to be rapidly labeled with biotin in the absence of enzyme. Nonenzymatic biotinylation of a truncated apocarboxylase (BCCP87) has been previously reported (Streaker and Beckett, Protein Sci 2006; 15:1928-1935), though at a much slower rate than we observe for H2A. The specific attachment sites of nonenzymatically biotinylated recombinant H2A at different time points were identified using mass spectrometry, and were found to consist of a similar pattern of biotin attachment as seen in the presence of HCS, with preference for lysines in the highly basic N-terminal region of the histone. None of the lysine sites within H2A resembles the biotin attachment consensus sequence seen in carboxylases, suggesting a novel mechanism for histone biotinylation.

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Section: Introductionmentioning

confidence: 99%

Nonenzymatic biotinylation of histone H2A

et al. 2009

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“…During evolution, mammals lost the ability to synthesize biotin and now satisfy their need for the vitamin through a delicate balance between dietary biotin and reutilization of endogenous, protein-bound biotin (1,2). To ensure a continuous supply of the vitamin, eukaryotic organisms have developed a biotin utilization cycle that depends on the participation of three different proteins.…”

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confidence: 99%

Paradoxical Regulation of Biotin Utilization in Brain and Liver and Implications for Inherited Multiple Carboxylase Deficiency

Pacheco‐Alvarez

Solorzano–Vargas

Gravel

et al. 2004

Journal of Biological Chemistry

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Holocarboxylase synthetase (HCS) catalyzes the biotinylation of five carboxylases in human cells, and mutations of HCS cause multiple carboxylase deficiency (MCD). Although HCS also participates in the regulation of its own mRNA levels, the relevance of this mechanism to normal metabolism or to the MCD phenotype is not known. In this study, we show that mRNA levels of enzymes involved in biotin utilization, including HCS, are down-regulated during biotin deficiency in liver while remaining constitutively expressed in brain. We propose that this mechanism of regulation is aimed at sparing the essential function of biotin in the brain at the expense of organs such as liver and kidney during biotin deprivation. In MCD, it is possible that some of the manifestations of the disease may be associated with downregulation of biotin utilization in liver because of the impaired activity of HCS and that high dose biotin therapy may in part be important to overcoming the adverse regulatory impact in such organs.

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“…These enzymes catalyze significant metabolic reactions and they play an important role in biochemical processes such as gluconeogenesis, lipogenesis, aminoacid metabolism and energy transduction. 1 Biotin is synthesized by the normal microflora of the large intestine and is partly absorbed in the colon. Avidin, a glycoprotein found in egg whites, binds biotin very specifically and tightly (Kd = 10 -15 M).…”

Section: Biotinmentioning

confidence: 99%

Development of an Egg-white Bioassay for Monitoring Biotin Levels in Urine and Serum

et al. 2007

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This article reports on the development of a simple and cost-effective bioassay for the detection of biotin in urine and serum, based on the very selective binding of avidin and biotin. Avidin was allowed to react without isolating it from egg white. Egg white was treated with the dye HABA, which binds to avidin. Upon subsequent treatment with biotin, HABA is released due to the high affinity of biotin to avidin. The amount of HABA released is proportional to the amount of biotin used.

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Biotin in Metabolism and Its Relationship to Human Disease

Cited by 120 publications

References 84 publications

Nonenzymatic biotinylation of histone H2A

Nonenzymatic biotinylation of histone H2A

Paradoxical Regulation of Biotin Utilization in Brain and Liver and Implications for Inherited Multiple Carboxylase Deficiency

Development of an Egg-white Bioassay for Monitoring Biotin Levels in Urine and Serum

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