Advertisement

Effects of Biotin Deprivation and Biotin Supplementation

  • Krishnamurti Dakshinamurti
  • Shyamala Dakshinamurti
  • Michael P. CzubrytEmail author
Living reference work entry

Abstract

A number of key carboxylase enzymes involved in metabolism depend upon the vitamin biotin for their structure and function. Humans and animals require biotin to be supplied in the diet. Biotin deficiency is relatively rare in the developed world and typically reflects consumption of egg white-enriched or ketogenic diets, whereas deficiency in underdeveloped countries is more likely to be due to biotin-poor diets. The effects of biotin deficiency are not typically life-threatening, but can lead to developmental delays in children, or hair and skin abnormalities in affected individuals. In contrast, biotin supplementation has been shown to provide salutary benefit in some individuals, such as diabetics. Here we examine the biochemistry of biotin, as well as the effects of biotin deficiency and supplementation, with a focus on human health.

Keywords

Biotin Prosthetic group Carboxylases Multiple carboxylase deficiency Glucose metabolism Cell differentiation and proliferation Pancreatic inflammatory proteins Pharmacological effects 

List of Abbreviations

ACC

Acetyl-CoA carboxylase

ATP

Adenosine triphosphate

HCS

Holocarboxylase synthetase

MCC

β-methylcrotonyl-CoA carboxylase

MCD

Multiple carboxylase deficiency

PAP

Pancreatitis-associated protein

PC

Pyruvate carboxylase

PCC

Propionyl-CoA carboxylase

PEPCK

Phosphoenolpyruvate carboxykinase

SMVT

Sodium-dependent multivitamin transporter

References

  1. Abu-Elheiga L, Matzuk MM, Abo-Hashema KA et al (2001) Continuous fatty acid oxidation and reduced fat storage in mice lacking acetyl-CoA carboxylase 2. Science 291:2613–2616CrossRefPubMedGoogle Scholar
  2. Albarracin CA, Fuqua BC, Evans JL et al (2008) Chromium picolinate and biotin combination improves glucose metabolism in treated, uncontrolled overweight to obese patients with type 2 diabetes. Diabetes Metab Res Rev 24:41–51CrossRefPubMedGoogle Scholar
  3. Atamna H, Newberry J, Erlitzki R et al (2007) Biotin deficiency inhibits heme synthesis and impairs mitochondria in human lung fibroblasts. J Nutr 137:25–30PubMedGoogle Scholar
  4. Baez-Saldana A, Camacho-Arroyo I, Espinosa-Aguirre JJ et al (2009) Biotin deficiency and biotin excess: effects on the female reproductive system. Steroids 74:863–869CrossRefPubMedGoogle Scholar
  5. Bowers-Komro DM, Mccormick DB (1985) Biotin uptake by isolated rat liver hepatocytes. Ann N Y Acad Sci 447:350–358CrossRefPubMedGoogle Scholar
  6. Chalifour LE, Dakshinamurti K (1982) The biotin requirement of human fibroblasts in culture. Biochem Biophys Res Commun 104:1047–1053CrossRefPubMedGoogle Scholar
  7. Chauhan J, Dakshinamurti K (1986) Purification and characterization of human serum biotinidase. J Biol Chem 261:4268–4275PubMedGoogle Scholar
  8. Chauhan J, Dakshinamurti K (1988) Role of human serum biotinidase as biotin-binding protein. Biochem J 256:265–270CrossRefPubMedPubMedCentralGoogle Scholar
  9. Chauhan J, Dakshinamurti K (1991) Transcriptional regulation of the glucokinase gene by biotin in starved rats. J Biol Chem 266:10035–10038PubMedGoogle Scholar
  10. Christeller JT, Markwick NP, Burgess EP et al (2010) The use of biotin-binding proteins for insect control. J Econ Entomol 103:497–508CrossRefPubMedGoogle Scholar
  11. Closa D, Motoo Y, Iovanna JL (2007) Pancreatitis-associated protein: from a lectin to an anti-inflammatory cytokine. World J Gastroenterol 13:170–174CrossRefPubMedPubMedCentralGoogle Scholar
  12. Dakshinamurti K (2005) Biotin – a regulator of gene expression. J Nutr Biochem 16:419–423CrossRefPubMedGoogle Scholar
  13. Dakshinamurti K, Allan L (1979) Isotope dilution assay for biotin: use of [3H]biotin. Methods Enzymol 62:284–287CrossRefPubMedGoogle Scholar
  14. Dakshinamurti K, Chalifour LE (1981) The biotin requirement of HeLa cells. J Cell Physiol 107:427–438CrossRefPubMedGoogle Scholar
  15. Dakshinamurti K, Chauhan J (1988) Regulation of biotin enzymes. Annu Rev Nutr 8:211–233CrossRefPubMedGoogle Scholar
  16. Dakshinamurti K, Chauhan J (1989) Biotin. Vitam Horm 45:337–384CrossRefPubMedGoogle Scholar
  17. Dakshinamurti K, Chauhan J (1990) Nonavidin biotin-binding proteins. Methods Enzymol 184:93–102CrossRefPubMedGoogle Scholar
  18. Dakshinamurti K, Cheah-Tan C (1968a) Biotin-mediated synthesis of hepatic glucokinase in the rat. Arch Biochem Biophys 127:17–21CrossRefPubMedGoogle Scholar
  19. Dakshinamurti K, Cheah-Tan C (1968b) Liver glucokinase of the biotin deficient rat. Can J Biochem 46:75–80CrossRefPubMedGoogle Scholar
  20. Dakshinamurti K, Ho Chong H (1970) Regulation of key hepatic glycolytic enzymes. Enzymol Biol Clin (Basel) 11:423–428CrossRefGoogle Scholar
  21. Dakshinamurti K, Li W (1994) Transcriptional regulation of liver phosphoenolpyruvate carboxykinase by biotin in diabetic rats. Mol Cell Biochem 132:127–132CrossRefPubMedGoogle Scholar
  22. Dakshinamurti K, Mistry SP (1963a) Amino acid incorporation and biotin deficiency. J Biol Chem 238:297–301PubMedGoogle Scholar
  23. Dakshinamurti K, Mistry SP (1963b) Tissue and intracellular distribution of biotin-C-1400H in rats and chicks. J Biol Chem 238:294–296PubMedGoogle Scholar
  24. Dakshinamurti K, Rector ES (1990) Monoclonal antibody to biotin. Methods Enzymol 184:111–119CrossRefPubMedGoogle Scholar
  25. Dakshinamurti K, Sabir MA, Bhuvaneswaran C (1970) Oxidative phosphorylation by biotin-deficient rat liver mitochondria. Arch Biochem Biophys 137:30–37CrossRefPubMedGoogle Scholar
  26. Dakshinamurti K, Landman AD, Ramamurti L et al (1974) Isotope dilution assay for biotin. Anal Biochem 61:225–231CrossRefPubMedGoogle Scholar
  27. Dakshinamurti K, Bhullar RP, Scoot A et al (1986) Production and characterization of a monoclonal antibody to biotin. Biochem J 237:477–482CrossRefPubMedPubMedCentralGoogle Scholar
  28. Dakshinamurti K, Chauhan J, Ebrahim H (1987) Intestinal absorption of biotin and biocytin in the rat. Biosci Rep 7:667–673CrossRefPubMedGoogle Scholar
  29. Dakshinamurti K, Bagchi RA, Abrenica B et al (2015) Microarray analysis of pancreatic gene expression during biotin repletion in biotin-deficient rats. Can J Physiol Pharmacol 93:1103–1110CrossRefPubMedGoogle Scholar
  30. De La Vega LA, Stockert RJ (2000) Regulation of the insulin and asialoglycoprotein receptors via cGMP-dependent protein kinase. Am J Physiol Cell Physiol 279:C2037–C2042Google Scholar
  31. Dundas CM, Demonte D, Park S (2013) Streptavidin-biotin technology: improvements and innovations in chemical and biological applications. Appl Microbiol Biotechnol 97:9343–9353CrossRefPubMedGoogle Scholar
  32. Dusetti NJ, Tomasini R, Azizi A et al (2000) Expression profiling in pancreas during the acute phase of pancreatitis using cDNA microarrays. Biochem Biophys Res Commun 277:660–667CrossRefPubMedGoogle Scholar
  33. Gravel RA, Narang MA (2005) Molecular genetics of biotin metabolism: old vitamin, new science. J Nutr Biochem 16:428–431CrossRefPubMedGoogle Scholar
  34. Kuroishi T (2015) Regulation of immunological and inflammatory functions by biotin. Can J Physiol Pharmacol 93:1091–1096CrossRefPubMedGoogle Scholar
  35. Larrieta E, Vega-Monroy ML, Vital P et al (2012) Effects of biotin deficiency on pancreatic islet morphology, insulin sensitivity and glucose homeostasis. J Nutr Biochem 23:392–399CrossRefPubMedGoogle Scholar
  36. Lazo De La Vega-Monroy ML, Larrieta E, German MS et al (2013) Effects of biotin supplementation in the diet on insulin secretion, islet gene expression, glucose homeostasis and beta-cell proportion. J Nutr Biochem 24:169–177CrossRefPubMedGoogle Scholar
  37. Lin S, Cronan JE (2011) Closing in on complete pathways of biotin biosynthesis. Mol BioSyst 7:1811–1821CrossRefPubMedGoogle Scholar
  38. Mann S, Ploux O (2011) Pyridoxal-5′-phosphate-dependent enzymes involved in biotin biosynthesis: structure, reaction mechanism and inhibition. Biochim Biophys Acta 1814:1459–1466CrossRefPubMedGoogle Scholar
  39. Mock DM, Dyken ME (1997) Biotin catabolism is accelerated in adults receiving long-term therapy with anticonvulsants. Neurology 49:1444–1447CrossRefPubMedGoogle Scholar
  40. Narang MA, Dumas R, Ayer LM et al (2004) Reduced histone biotinylation in multiple carboxylase deficiency patients: a nuclear role for holocarboxylase synthetase. Hum Mol Genet 13:15–23CrossRefPubMedGoogle Scholar
  41. Oh W, Abu-Elheiga L, Kordari P et al (2005) Glucose and fat metabolism in adipose tissue of acetyl-CoA carboxylase 2 knockout mice. Proc Natl Acad Sci U S A 102:1384–1389CrossRefPubMedPubMedCentralGoogle Scholar
  42. Ortega-Cuellar D, Hernandez-Mendoza A, Moreno-Arriola E et al (2010) Biotin starvation with adequate glucose provision causes paradoxical changes in fuel metabolism gene expression similar in rat (Rattus norvegicus), nematode (Caenorhabditis elegans) and yeast (Saccharomyces cerevisiae). J Nutrigenet Nutrigenomics 3:18–30CrossRefPubMedGoogle Scholar
  43. Pacheco-Alvarez D, Solorzano-Vargas RS, Gravel RA et al (2004) Paradoxical regulation of biotin utilization in brain and liver and implications for inherited multiple carboxylase deficiency. J Biol Chem 279:52312–52318CrossRefPubMedGoogle Scholar
  44. Paulose CS, Thliveris JA, Viswanathan M et al (1989) Testicular function in biotin-deficient adult rats. Horm Metab Res 21:661–665CrossRefPubMedGoogle Scholar
  45. Romero-Navarro G, Cabrera-Valladares G, German MS et al (1999) Biotin regulation of pancreatic glucokinase and insulin in primary cultured rat islets and in biotin-deficient rats. Endocrinology 140:4595–4600CrossRefPubMedGoogle Scholar
  46. Roth KS (1985) Prenatal treatment of multiple carboxylase deficiency. Ann NY Acad Sci 447:263–271CrossRefPubMedGoogle Scholar
  47. Roth KS, Yang W, Allan L et al (1982) Prenatal administration of biotin in biotin responsive multiple carboxylase deficiency. Pediatr Res 16:126–129CrossRefPubMedGoogle Scholar
  48. Sato Y, Wakabayashi K, Ogawa E et al (2016) Low serum biotin in Japanese children fed with hydrolysate formula. Pediatr Int 58:867–871CrossRefPubMedGoogle Scholar
  49. Singer GM, Geohas J (2006) The effect of chromium picolinate and biotin supplementation on glycemic control in poorly controlled patients with type 2 diabetes mellitus: a placebo-controlled, double-blinded, randomized trial. Diabetes Technol Ther 8:636–643CrossRefPubMedGoogle Scholar
  50. Singh IN, Dakshinamurti K (1988) Stimulation of guanylate cyclase and RNA polymerase II activities in HeLa cells and fibroblasts by biotin. Mol Cell Biochem 79:47–55CrossRefPubMedGoogle Scholar
  51. Skamnioti P, Gurr SJ (2009) Against the grain: safeguarding rice from rice blast disease. Trends Biotechnol 27:141–150CrossRefPubMedGoogle Scholar
  52. Spence JT, Koudelka AP (1984) Effects of biotin upon the intracellular level of cGMP and the activity of glucokinase in cultured rat hepatocytes. J Biol Chem 259:6393–6396PubMedGoogle Scholar
  53. Stanley JS, Griffin JB, Zempleni J (2001) Biotinylation of histones in human cells. Effects of cell proliferation. Eur J Biochem 268:5424–5429CrossRefPubMedGoogle Scholar
  54. Stratton SL, Horvath TD, Bogusiewicz A et al (2011) Urinary excretion of 3-hydroxyisovaleryl carnitine is an early and sensitive indicator of marginal biotin deficiency in humans. J Nutr 141:353–358CrossRefPubMedPubMedCentralGoogle Scholar
  55. Sugita Y, Shirakawa H, Sugimoto R et al (2008) Effect of biotin treatment on hepatic gene expression in streptozotocin-induced diabetic rats. Biosci Biotechnol Biochem 72:1290–1298CrossRefPubMedGoogle Scholar
  56. Sweetman L, Nyhan WL (1986) Inheritable biotin-treatable disorders and associated phenomena. Annu Rev Nutr 6:317–343CrossRefPubMedGoogle Scholar
  57. Takakura Y, Oka N, Suzuki J et al (2012) Intercellular production of tamavidin 1, a biotin-binding protein from Tamogitake mushroom, confers resistance to the blast fungus Magnaporthe oryzae in transgenic rice. Mol Biotechnol 51:9–17CrossRefPubMedGoogle Scholar
  58. Terouanne B, Bencheick M, Balaguer P et al (1989) Bioluminescent assays using glucose-6-phosphate dehydrogenase: application to biotin and streptavidin detection. Anal Biochem 180:43–49CrossRefPubMedGoogle Scholar
  59. Thuy LP, Sweetman L, Nyhan WL (1991) A new immunochemical assay for biotin. Clin Chim Acta 202:191–197CrossRefPubMedGoogle Scholar
  60. Tong L (2005) Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery. Cell Mol Life Sci 62:1784–1803CrossRefPubMedGoogle Scholar
  61. Tong L (2013) Structure and function of biotin-dependent carboxylases. Cell Mol Life Sci 70:863–891CrossRefPubMedGoogle Scholar
  62. Tong L, Harwood HJ Jr (2006) Acetyl-coenzyme A carboxylases: versatile targets for drug discovery. J Cell Biochem 99:1476–1488CrossRefPubMedGoogle Scholar
  63. Vasseur S, Folch-Puy E, Hlouschek V et al (2004) p8 improves pancreatic response to acute pancreatitis by enhancing the expression of the anti-inflammatory protein pancreatitis-associated protein I. J Biol Chem 279:7199–7207CrossRefPubMedGoogle Scholar
  64. Velazquez-Arellano A, Hernandez-Esquivel Mde L, Sanchez RM et al (2008) Functional and metabolic implications of biotin deficiency for the rat heart. Mol Genet Metab 95:213–219CrossRefPubMedGoogle Scholar
  65. Velazquez-Arellano A, Ortega-Cuellar D, Hernandez-Mendoza A et al (2011) A heuristic model for paradoxical effects of biotin starvation on carbon metabolism genes in the presence of abundant glucose. Mol Genet Metab 102:69–77CrossRefPubMedGoogle Scholar
  66. Wakabayashi K, Kodama H, Ogawa E et al (2016) Serum biotin in Japanese children: enzyme-linked immunosorbent assay measurement. Pediatr Int 58:872–876CrossRefPubMedGoogle Scholar
  67. Watanabe T, Dakshinamurti K, Persaud TV (1995) Biotin influences palatal development of mouse embryos in organ culture. J Nutr 125:2114–2121PubMedGoogle Scholar
  68. Watanabe-Kamiyama M, Kamiyama S, Horiuchi K et al (2008) Antihypertensive effect of biotin in stroke-prone spontaneously hypertensive rats. Br J Nutr 99:756–763CrossRefPubMedGoogle Scholar
  69. Wiedmann S, Eudy JD, Zempleni J (2003) Biotin supplementation increases expression of genes encoding interferon-gamma, interleukin-1beta, and 3-methylcrotonyl-CoA carboxylase, and decreases expression of the gene encoding interleukin-4 in human peripheral blood mononuclear cells. J Nutr 133:716–9PubMedGoogle Scholar
  70. Wolf B (2011) The neurology of biotinidase deficiency. Mol Genet Metab 104:27–34CrossRefPubMedGoogle Scholar
  71. Wolf B (2015) Biotinidase deficiency should be considered in individuals exhibiting myelopathy with or without and vision loss. Mol Genet Metab 116:113–118CrossRefPubMedGoogle Scholar
  72. Yuasa M, Matsui T, Ando S et al (2013) Consumption of a low-carbohydrate and high-fat diet (the ketogenic diet) exaggerates biotin deficiency in mice. Nutrition 29:1266–1270CrossRefPubMedGoogle Scholar
  73. Zhang H, Kandil E, Lin YY et al (2004) Targeted inhibition of gene expression of pancreatitis-associated proteins exacerbates the severity of acute pancreatitis in rats. Scand J Gastroenterol 39:870–881CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • Krishnamurti Dakshinamurti
    • 2
  • Shyamala Dakshinamurti
    • 3
  • Michael P. Czubryt
    • 1
    Email author
  1. 1.Department of Physiology and Pathophysiology, Institute of Cardiovascular Sciences, St. Boniface Hospital Albrechtsen Research CentreUniversity of ManitobaWinnipegCanada
  2. 2.Department of Biochemistry and Medical GeneticsSt. Boniface Hospital Albrechtsen Research Centre, University of ManitobaWinnipegCanada
  3. 3.Departments of Pediatrics and Physiology, Biology of Breathing Group, Manitoba Institute of Child HealthUniversity of ManitobaWinnipegCanada

Personalised recommendations