The Experts below are selected from a list of 291 Experts worldwide ranked by ideXlab platform
Barry Wolf - One of the best experts on this subject based on the ideXlab platform.
-
Biotinidase deficiency should be considered in individuals thought to have multiple sclerosis and related disorders
Multiple sclerosis and related disorders, 2019Co-Authors: Barry WolfAbstract:Abstract Background Multiple sclerosis is a disorder of the central and peripheral nervous system of young and old adults that is characterized by muscle, coordination and vision abnormalities. Multiple sclerosis is likely due to numerous causes. Methods Recently, adolescents and adults with ophthalmological and or neurological findings have been diagnosed with Biotinidase deficiency. These individuals have exhibited myelopathy, paresis and/or spastic diplegia/tetraplegia with or without optic neuropathy/vision loss. These older individuals with Biotinidase deficiency were considered initially to have multiple sclerosis or similar disorders before they were determined to have Biotinidase deficiency. Results If a symptomatic individual with Biotinidase deficiency is treated with biotin early enough, the symptoms markedly improve or completely resolve, but if treatment is delayed, the symptoms may be irreversible. Conclusion Therefore, although Biotinidase deficiency is rare relative to that of multiple sclerosis, the disorder should be included in the differential diagnosis of individuals thought to have multiple sclerosis or related disorders. Biotinidase deficiency should be considered in individuals thought to have multiple sclerosis or related disorders.
-
successful outcomes of older adolescents and adults with profound Biotinidase deficiency identified by newborn screening
Genetics in Medicine, 2017Co-Authors: Barry WolfAbstract:We began screening newborns for Biotinidase deficiency disorder in 1984, and now all states in the United States and many countries perform this screening. The purpose of this study was to determine the outcomes of older adolescent and adult individuals with the disorder identified by newborn screening. We located and surveyed, by questionnaire and telephone interviews, 44 individuals with profound Biotinidase deficiency identified by newborn screening with a mean age of 23.1 years. All individuals had successfully completed high school, and many were attending or had completed college or graduate school. Compliance in using biotin has been excellent. Several individuals developed a variety of symptoms when they discontinued biotin for days or weeks. These features readily resolved when biotin was resumed. In addition, five treated women had nine uneventful pregnancies and deliveries. Newborn screening for profound Biotinidase deficiency and early treatment with biotin result in excellent outcomes for older adolescents and adults with the disorder. In addition, mothers with profound Biotinidase deficiency who were treated with biotin had pregnancies with good outcomes. These outcome results indicate that newborn screening for Biotinidase deficiency is one of the most successful newborn screening programs. Genet Med 19 4, 396–402.
-
irreversibility of symptoms with biotin therapy in an adult with profound Biotinidase deficiency
JIMD reports, 2017Co-Authors: Patrick Ferreira, Barry Wolf, Alicia ChanAbstract:We report a 36-year-old woman who exhibited progressive optic atrophy at 13 years old, then stroke-like episodes and spastic diplegia in her 20s. Biotinidase deficiency was not readily considered in the differential diagnosis, and the definitive diagnosis was not made until pathological variants of the Biotinidase gene (BTD) were found by exome sequencing. Profound Biotinidase deficiency was confirmed by enzyme analysis. Unfortunately, her symptoms did not resolve or improve with biotin treatment. Biotin therapy is essential for all individuals with profound Biotinidase deficiency and for preventing further damage in those who already exhibit irreversible neurological damage. Newborn screening for the disorder would have avoided years of clinical symptoms that now appear to be irreversible with biotin treatment.
-
Biotinidase deficiency should be considered in individuals exhibiting myelopathy with or without and vision loss
Molecular Genetics and Metabolism, 2015Co-Authors: Barry WolfAbstract:Multiple symptomatic children with Biotinidase deficiency have exhibited spastic para- or tetraplegia due to myelopathy with and without vision loss. Although this has been a feature of what has been designated as delayed onset-Biotinidase deficiency, myelopathy is likely also on the continuum of clinical features seen in younger children who have had these features attributed to dysfunction of the upper brain rather than of the spinal cord. Because many countries are still not screening their newborns for Biotinidase deficiency, the disorder should be included in the differential diagnosis of individuals with myelopathic symptoms. Many of these children have gone weeks to months before they were correctly diagnosed with Biotinidase deficiency. Rapid recognition that a child with myelopathy with and without vision loss has Biotinidase deficiency will undoubtedly facilitate prompt treatment, increase the possibility of complete recovery and avoid potential residual permanent neurological damage. Newborn screening for Biotinidase deficiency would avoid the delay in the diagnosis and treatment of individuals who otherwise may present with myelopathic or other neurological symptoms.
-
why screen newborns for profound and partial Biotinidase deficiency
Molecular Genetics and Metabolism, 2015Co-Authors: Barry WolfAbstract:Newborn screening for Biotinidase deficiency is currently performed throughout the United States and inmany countries of the world. However, there are still many countries that do not screen for the disorder. After learning howmany countries are still not screening for Biotinidase deficiency, and after I received the comments on a recently submitted publication, I was compelled to address twomajor concerns about newborn screening for the disorder. The first is why should a country screen their newborns for profound Biotinidase deficiency (less than 10% of mean normal serum enzyme activity)? The second is, if a country screens their newborns for profound Biotinidase deficiency, why should they also screen for partial Biotinidase deficiency (between10% and 30% of mean normal serum enzyme activity)? Before addressing these issues, Iwould like to state that over thepast 32 years, my research has focused on the study of the clinical, biochemical and molecular aspects of Biotinidase deficiency. Even though my laboratory developed the colorimetric assay for Biotinidase activity using blood-soaked filter paper cards, and we conducted the first newborn screening program in Virginia, I have not received, nor do I currently receive, any compensation for any aspect of newborn screening of the disorder. This being said, I would like to address the above questions. Why screen newborns for profound Biotinidase deficiency? Since the discovery of Biotinidase deficiency in our laboratory in 1982 [1,2], there has been a rapid transition from the development of a colorimetric method for determining Biotinidase activity using blood-soaked filter paper spots [3] to the demonstration of the feasibility of performing
Paul G. Walfish - One of the best experts on this subject based on the ideXlab platform.
-
Biotinidase is a Novel Marker for Papillary Thyroid Cancer Aggressiveness
PLOS ONE, 2012Co-Authors: Anthony K.-c. So, Jatinder Kaur, Jasmeet Assi, Christina Macmillan, Ranju Ralhan, Paul G. WalfishAbstract:: Biotinidase was identified in secretome analysis of thyroid cancer cell lines using proteomics. The goal of the current study was to analyze the expression of Biotinidase in thyroid cancer tissues and fine needle aspiration (FNA) samples to evaluate its diagnostic and prognostic potential in thyroid cancer. Immunohistochemical analysis of Biotinidase was carried out in 129 papillary thyroid cancer (PTC, 34 benign thyroid tissues and 43 FNA samples and correlated with patients' prognosis. Overall Biotinidase expression was decreased in PTC compared to benign nodules (p = 0.001). Comparison of aggressive and non-aggressive PTC showed decrease in overall Biotinidase expression in the former (p = 0.001). Loss of overall Biotinidase expression was associated with poor disease free survival (p = 0.019, Hazards ratio (HR) = 3.1). We examined the effect of subcellular compartmentalization of nuclear and cytoplasmic Biotinidase on patient survival. Decreased nuclear expression of Biotinidase was observed in PTC as compared to benign tissues (p
-
Biotinidase is a novel marker for papillary thyroid cancer aggressiveness
PLOS ONE, 2012Co-Authors: Anthony K.-c. So, Jatinder Kaur, Jasmeet Assi, Christina Macmillan, Ranju Ralhan, Paul G. WalfishAbstract:: Biotinidase was identified in secretome analysis of thyroid cancer cell lines using proteomics. The goal of the current study was to analyze the expression of Biotinidase in thyroid cancer tissues and fine needle aspiration (FNA) samples to evaluate its diagnostic and prognostic potential in thyroid cancer. Immunohistochemical analysis of Biotinidase was carried out in 129 papillary thyroid cancer (PTC, 34 benign thyroid tissues and 43 FNA samples and correlated with patients' prognosis. Overall Biotinidase expression was decreased in PTC compared to benign nodules (p = 0.001). Comparison of aggressive and non-aggressive PTC showed decrease in overall Biotinidase expression in the former (p = 0.001). Loss of overall Biotinidase expression was associated with poor disease free survival (p = 0.019, Hazards ratio (HR) = 3.1). We examined the effect of subcellular compartmentalization of nuclear and cytoplasmic Biotinidase on patient survival. Decreased nuclear expression of Biotinidase was observed in PTC as compared to benign tissues (p<0.001). Upon stratification within PTC, nuclear expression was reduced in aggressive as compared to non-aggressive tumors (p<0.001). Kaplan-Meier survival analysis showed significant association of loss of nuclear Biotinidase expression with reduced disease free survival (p = 0.014, HR = 5.4). Cytoplasmic Biotinidase expression was reduced in aggressive thyroid cancers in comparison with non-aggressive tumors (p = 0.002, Odds ratio (OR) = 0.29) which was evident by its significant association with advanced T stage (p = 0.003, OR = 0.28), nodal metastasis (p<0.001, OR = 0.16), advanced TNM stage (p<0.001, OR = 0.21) and extrathyroidal extension (p = 0.001, OR = 0.23). However, in multivariate analysis extrathyroidal extension emerged as the most significant prognostic marker for aggressive thyroid carcinomas (p = 0.015, HR = 12.8). In conclusion, loss of overall Biotinidase expression is a novel marker for thyroid cancer aggressiveness.
Kirit Pindolia - One of the best experts on this subject based on the ideXlab platform.
-
characterization and functional analysis of cellular immunity in mice with Biotinidase deficiency
Molecular Genetics and Metabolism, 2014Co-Authors: Barry Wolf, Kirit Pindolia, Hong Li, Cisley CardwellAbstract:Abstract Biotinidase deficiency is an autosomal recessively inherited metabolic disorder that can be easily and effectively treated with pharmacological doses of the vitamin, biotin. Untreated children with profound Biotinidase deficiency may exhibit neurological, cutaneous and cellular immunological abnormalities, specifically candida infections. To better understand the immunological dysfunction in some symptomatic individuals with Biotinidase deficiency, we studied various aspects of immunological function in a genetically engineered knock-out mouse with Biotinidase deficiency. The mouse has no detectable Biotinidase activity and develops neurological and cutaneous symptoms similar to those seen in symptomatic children with the disorder. Mice with profound Biotinidase deficiency on a biotin-restricted diet had smaller thymuses and spleens than identical mice fed a biotin-replete diet or wildtype mice on either diet; however, the organ to body weight ratios were not significantly different. Thymus histology was normal. Splenocyte subpopulation study showed a significant increase in CD4 positive cells. In addition, in vitro lymphocyte proliferation assays consistently showed diminished proliferation in response to various immunological stimuli. Not all symptomatic individuals with profound Biotinidase deficiency develop immunological dysfunction; however, our results do show significant alterations in cellular immunological function that may contribute and/or provide a mechanism(s) for the cellular immunity abnormalities in individuals with Biotinidase deficiency.
-
Biotinidase knockout mice show cellular energy deficit and altered carbon metabolism gene expression similar to that of nutritional biotin deprivation clues for the pathogenesis in the human inherited disorder
Molecular Genetics and Metabolism, 2013Co-Authors: Alain De J Hernandezvazquez, Barry Wolf, Kirit Pindolia, Daniel Ortegacuellar, R Hernandezgonzalez, A Herediaantunez, Isabel Ibarragonzalez, Antonio VelazquezarellanoAbstract:Abstract Biotin is the prosthetic group of carboxylases that have important roles in the metabolism of glucose, fatty acids and amino acids. Biotinidase has a key role in the reutilization of the biotin, catalyzing the hydrolysis of biocytin (e-N-biotinyl- l -lysine) and biocytin-containing peptides derived from carboxylase turnover, thus contributing substantially to the bioavailability of this vitamin. Deficient activity of Biotinidase causes late-onset multiple carboxylase in humans, whose pathogenic mechanisms are poorly understood. Here we show that a knock-out Biotinidase-deficient mouse from a C57BL/6 background that was fed a low biotin diet develops severe ATP deficit with activation of the energy sensor adenosine monophosphate (AMP)-activated protein kinase (AMPK), inhibition of the signaling protein mTOR, driver of protein synthesis and growth, and affecting the expression of central-carbon metabolism genes. In addition, sensitivity to insulin is augmented. These changes are similar to those observed in nutritionally biotin-starved rats. These findings further our understanding of the pathogenesis of human Biotinidase deficiency.
-
neurological deficits in mice with profound Biotinidase deficiency are associated with demylination and axonal degeneration
Neurobiology of Disease, 2012Co-Authors: Kirit Pindolia, Barry Wolf, Cisley Cardwell, Jieli Chen, Michael ChoppAbstract:Biotinidase deficiency is an autosomal recessively inherited disorder characterized by neurological and cutaneous abnormalities. We have developed a transgenic knock-out mouse with Biotinidase deficiency to better understand aspects of pathophysiology and natural history of the disorder in humans. Neurological deficits observed in symptomatic mice with Biotinidase deficiency are similar to those seen in symptomatic children with the disorder. Using a battery of functional neurological assessment tests, the symptomatic mice performed poorly compared to wild-type mice. Demyelination, axonal degeneration, ventriculomegaly, and corpus callosum compression were found in the brains of untreated, symptomatic enzyme-deficient mice. With biotin treatment, the symptomatic mice improved neurologically and the white matter abnormalities resolved. These functional and anatomical findings and their reversal with biotin therapy are similar to those observed in untreated, symptomatic and treated individuals with Biotinidase deficiency. The mouse with Biotinidase deficiency appears to be an appropriate animal model in which to study the neurological abnormalities and the effects of treatment of the disorder.
-
development and characterization of a mouse with profound Biotinidase deficiency a biotin responsive neurocutaneous disorder
Molecular Genetics and Metabolism, 2011Co-Authors: Kirit Pindolia, Barry Wolf, Megan Jordan, Miriam G Blitzer, Nell I Matthews, Donald M Mock, Erin T StrovelAbstract:Biotinidase deficiency is the primary enzymatic defect in biotin-responsive, late-onset multiple carboxylase deficiency. Untreated children with profound Biotinidase deficiency usually exhibit neurological symptoms including lethargy, hypotonia, seizures, developmental delay, sensorineural hearing loss and optic atrophy; and cutaneous symptoms including skin rash, conjunctivitis and alopecia. Although the clinical features of the disorder markedly improve or are prevented with biotin supplementation, some symptoms, once they occur, such as developmental delay, hearing loss and optic atrophy, are usually irreversible. To prevent development of symptoms, the disorder is screened for in the newborn period in essentially all states and in many countries. In order to better understand many aspects of the pathophysiology of the disorder, we have developed a transgenic Biotinidase-deficient mouse. The mouse has a null mutation that results in no detectable serum Biotinidase activity or cross-reacting material to antibody prepared against Biotinidase. When fed a biotin-deficient diet these mice develop neurological and cutaneous symptoms, carboxylase deficiency, mild hyperammonemia, and exhibit increased urinary excretion of 3-hydroxyisovaleric acid and biotin and biotin metabolites. The clinical features are reversed with biotin supplementation. This Biotinidase-deficient animal can be used to study systematically many aspects of the disorder and the role of Biotinidase, biotin and biocytin in normal and in enzyme-deficient states.
-
analysis of mutations causing Biotinidase deficiencya
Human Mutation, 2010Co-Authors: Barry Wolf, Kirit Pindolia, Megan JordanAbstract:Biotinidase deficiency is an inherited disorder in which the vitamin, biotin, is not recycled. Individuals with Biotinidase deficiency can develop neurological and cutaneous symptoms if they are not treated with biotin. Biotinidase deficiency screening has been incorporated into essentially all newborn screening programs in the United States and in many countries. We now report 140 known mutations in the Biotinidase gene (BTD) that cause Biotinidase deficiency. All types of mutations have been found to cause Biotinidase deficiency. Variants have been identified throughout the coding sequence. Essentially all the variants result in enzymatic activities with less than 10% of mean normal enzyme activity (profound Biotinidase deficiency) with the exception of the c.1330G>C (p.D444H) mutation, which results in an enzyme having 50% of mean normal serum activity. The putative three-dimensional structure of Biotinidase has been predicted by homology to that of nitrilases/amidases. The effect of the various missense mutations can be predicted to affect various important sites within the structure of the enzyme. This compilation of variants causing Biotinidase deficiency will be useful to clinical laboratories that are performing mutation analysis for confirmational testing when the enzymatic results are equivocal for children identified through newborn screening. Hum Mutat 31:983–991, 2010. © 2010 Wiley-Liss, Inc.
Anthony K.-c. So - One of the best experts on this subject based on the ideXlab platform.
-
Biotinidase is a Novel Marker for Papillary Thyroid Cancer Aggressiveness
PLOS ONE, 2012Co-Authors: Anthony K.-c. So, Jatinder Kaur, Jasmeet Assi, Christina Macmillan, Ranju Ralhan, Paul G. WalfishAbstract:: Biotinidase was identified in secretome analysis of thyroid cancer cell lines using proteomics. The goal of the current study was to analyze the expression of Biotinidase in thyroid cancer tissues and fine needle aspiration (FNA) samples to evaluate its diagnostic and prognostic potential in thyroid cancer. Immunohistochemical analysis of Biotinidase was carried out in 129 papillary thyroid cancer (PTC, 34 benign thyroid tissues and 43 FNA samples and correlated with patients' prognosis. Overall Biotinidase expression was decreased in PTC compared to benign nodules (p = 0.001). Comparison of aggressive and non-aggressive PTC showed decrease in overall Biotinidase expression in the former (p = 0.001). Loss of overall Biotinidase expression was associated with poor disease free survival (p = 0.019, Hazards ratio (HR) = 3.1). We examined the effect of subcellular compartmentalization of nuclear and cytoplasmic Biotinidase on patient survival. Decreased nuclear expression of Biotinidase was observed in PTC as compared to benign tissues (p
-
Biotinidase is a novel marker for papillary thyroid cancer aggressiveness
PLOS ONE, 2012Co-Authors: Anthony K.-c. So, Jatinder Kaur, Jasmeet Assi, Christina Macmillan, Ranju Ralhan, Paul G. WalfishAbstract:: Biotinidase was identified in secretome analysis of thyroid cancer cell lines using proteomics. The goal of the current study was to analyze the expression of Biotinidase in thyroid cancer tissues and fine needle aspiration (FNA) samples to evaluate its diagnostic and prognostic potential in thyroid cancer. Immunohistochemical analysis of Biotinidase was carried out in 129 papillary thyroid cancer (PTC, 34 benign thyroid tissues and 43 FNA samples and correlated with patients' prognosis. Overall Biotinidase expression was decreased in PTC compared to benign nodules (p = 0.001). Comparison of aggressive and non-aggressive PTC showed decrease in overall Biotinidase expression in the former (p = 0.001). Loss of overall Biotinidase expression was associated with poor disease free survival (p = 0.019, Hazards ratio (HR) = 3.1). We examined the effect of subcellular compartmentalization of nuclear and cytoplasmic Biotinidase on patient survival. Decreased nuclear expression of Biotinidase was observed in PTC as compared to benign tissues (p<0.001). Upon stratification within PTC, nuclear expression was reduced in aggressive as compared to non-aggressive tumors (p<0.001). Kaplan-Meier survival analysis showed significant association of loss of nuclear Biotinidase expression with reduced disease free survival (p = 0.014, HR = 5.4). Cytoplasmic Biotinidase expression was reduced in aggressive thyroid cancers in comparison with non-aggressive tumors (p = 0.002, Odds ratio (OR) = 0.29) which was evident by its significant association with advanced T stage (p = 0.003, OR = 0.28), nodal metastasis (p<0.001, OR = 0.16), advanced TNM stage (p<0.001, OR = 0.21) and extrathyroidal extension (p = 0.001, OR = 0.23). However, in multivariate analysis extrathyroidal extension emerged as the most significant prognostic marker for aggressive thyroid carcinomas (p = 0.015, HR = 12.8). In conclusion, loss of overall Biotinidase expression is a novel marker for thyroid cancer aggressiveness.
Jeanne Hymes - One of the best experts on this subject based on the ideXlab platform.
-
identification of alternatively spliced human Biotinidase mrnas and putative localization of endogenous Biotinidase
Molecular Genetics and Metabolism, 2004Co-Authors: Christine M Stanley, Jeanne Hymes, Barry WolfAbstract:Abstract Biotinidase is essential for recycling the vitamin biotin and for transferring biotin to proteins, such as histones, suggesting that the enzyme localizes to various cellular and extracellular sites. To better understand the functions of the enzyme, we examined its gene structure and subcellular localization. Using RACE-PCR and a BLAST search, we extended the 5 ′ sequence of the Biotinidase gene. Three novel, alternatively spliced variants of Biotinidase, 1a, 1b, and 1c, were identified in multiple human tissues. Exon 1c is present only in testes. The sequence of the 5 ′ splice variants, 1a and 1b, suggest that Biotinidase localizes to the mitochondria and/or ER, respectively. Using indirect immunofluorescence studies, Biotinidase localizes to organelles in the cytoplasm, but not nucleus, of human fibroblasts and Hep G2 cells. Endogenous expression was examined by isopycnic gradient centrifugation of rat liver organelles, which identified an 85kDa Biotinidase protein with biotinyl-hydrolase and transferase activities in microsomes and possibly lysosomes. A 48kDa protein, which also reacts with anti-Biotinidase, localizes to mitochondria. The 48kDa protein is not N-glycosylated but is biotinylated, is in the inner mitochondrial matrix, but has no biotinyl-hydrolase or transferase activities. The function and validation of the mitochondrial species remains to be determined. The 5 ′ splice variants and organelle fractionation studies indicate that Biotinidase is directed to the secretory pathway and perhaps mitochondria.
-
Biotinidase IN SERUM AND TISSUES
Methods in Enzymology, 2004Co-Authors: Jeanne Hymes, Kristin Fleischhauer, Barry WolfAbstract:Publisher Summary This chapter describes the assays of Biotinidase hydrolytic activity. Natural and artificial substrates have been used in various assays of Biotinidase activity; these include secondary enzymatic, radiometric, colorimetric, and fluorometric measurements. Some methods require derivatization or chromatographic separation of the reaction products. Serum and tissues, such as liver with high Biotinidase activity, can be measured using the colorimetric assay. Biotinidase activity can also be measured in cultured cells, such as hepatocytes and fibroblasts, by this method. Biotinidase activity in tissues, such as peripheral blood leukocytes and brain, requires a more sensitive method, such as the radioassay. A high-performance liquid chromatography (HPLC) method for measuring Biotinidase activity using biotinyl-6-has been aminoquinoline as substrate developed. An HPLC radioassay uses biotinylmono[ 125 ]iodotyramine and biotinyldi[ 125 ]iodotyramine as substrates. The simplest and most commonly used method for measuring Biotinidase activity uses biotinyl- p -aminobenzoate (BPABA) as substrate. The chapter describes two methods that are based on measurement of the lipoyl- p -aminobenzoate (PABA) released from BPABA by the hydrolytic action of Biotinidase. The first method is usually used for the diagnosis of Biotinidase deficiency. The second method is 100-fold more sensitive than the colorimetric assay and can measure Biotinidase activity in tissues, such as leukocytes and amniotic cells that have low enzyme activities.
-
Amino acid homologies between human Biotinidase and bacterial aliphatic amidases: putative identification of the active site of Biotinidase.
Molecular Genetics and Metabolism, 2000Co-Authors: Katie L. Swango, Jeanne Hymes, Paul Brown, Barry WolfAbstract:Abstract A search of protein databases revealed amino acid homologies among human Biotinidase, bacterial aliphatic amidases, and bacterial and plant nitrilases. Amino acids YRK 210–212 of Biotinidase are conserved among the enzyme families. This homology and naturally occurring mutations that cause Biotinidase deficiency suggest that this region is essential for enzyme activity and is conserved from bacteria. Cys 245 is likely the cysteine in the active site of Biotinidase.
-
human Biotinidase isn t just for recycling biotin
Journal of Nutrition, 1999Co-Authors: Jeanne Hymes, Barry WolfAbstract:For years, the major role of biotin has been as the coenzyme for four carboxylases in humans. Although there has been evidence that biotin might have other functions, none has been firmly established. The discovery that human serum Biotinidase has biotinyl-transferase activity, in addition to Biotinidase hydrolase activity, presents new possibilities for the role of Biotinidase in biotin metabolism. Specific transfer of biotin to histones by Biotinidase provides a possible explanation for why biotin is found in the nucleus and the nature of its role in the regulation of protein transcription. Future studies will help to determine the functions of Biotinidase in biotin metabolism and in disease states.
-
Human Biotinidase Isn’t Just for Recycling Biotin
Journal of Nutrition, 1999Co-Authors: Jeanne Hymes, Barry WolfAbstract:For years, the major role of biotin has been as the coenzyme for four carboxylases in humans. Although there has been evidence that biotin might have other functions, none has been firmly established. The discovery that human serum Biotinidase has biotinyl-transferase activity, in addition to Biotinidase hydrolase activity, presents new possibilities for the role of Biotinidase in biotin metabolism. Specific transfer of biotin to histones by Biotinidase provides a possible explanation for why biotin is found in the nucleus and the nature of its role in the regulation of protein transcription. Future studies will help to determine the functions of Biotinidase in biotin metabolism and in disease states.