Abstract

Patients with biotin deficiency present symptoms that are similar to those in patients with acrodermatitis enteropathica (inherent zinc deficiency). However, the association between biotin and zinc deficiency remains unknown. We have previously shown that epidermal keratinocytes of mice fed zinc-deficient (ZD) diets secreted more adenosine triphosphate (ATP) than those of mice fed zinc-adequate (ZA) diets and that epidermal Langerhans cells are absent in ZD mice. Langerhans cells highly express CD39, which potently hydrolyzes ATP into adenosine monophosphate (AMP). Thus, a lack of Langerhans cells in ZD mice leads to non-hydrolysis of ATP, thereby leading to the development of ATP-mediated irritant contact dermatitis. In this study, we examined if biotin-deficient (BD) mice showed the same underlying mechanisms as those in ZD mice. BD mice showed reduced serum zinc levels, disappearance of epidermal Langerhans cells, and enhanced ATP production in the skin. Consequently, irritant contact dermatitis was significantly enhanced and prolonged in BD mice. In conclusion, the findings of our study showed that biotin deficiency leads to zinc deficiency because of which patients with biotin deficiency show similar symptoms as those with acrodermatitis enteropathica.

Highlights

  • Biotin is a water-soluble vitamin that serves as a co-enzyme for five carboxylases, namely, the covalently bound coenzyme for acetyl-CoA carboxylases 1 and 2, pyruvate carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase

  • Dietary Biotin Deficiency Leads to Zinc Deficiency

  • After 9 weeks of initiation of the BD diet, the serum zinc levels in BD mice were significantly reduced compared with those in BA mice (Figure 1B; right panel), and were almost comparable to those in ZD mice after 7 weeks of initiation of ZD diet (Figure 1B; left and right panels). These data suggest that dietary biotin deficiency (BnD) leads to zinc deficiency (ZnD)

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Summary

Introduction

Biotin is a water-soluble vitamin that serves as a co-enzyme for five carboxylases, namely, the covalently bound coenzyme for acetyl-CoA carboxylases 1 and 2, pyruvate carboxylase, propionyl-CoA carboxylase, and 3-methylcrotonyl-CoA carboxylase. These biotin-dependent carboxylases facilitate various metabolic reactions such as gluconeogenesis, fatty acid synthesis, and amino acid synthesis. Patients with BnD [4] are known to develop clinical symptoms that are similar to those in patients with acrodermatitis enteropathica (AE), which is caused by loss-of-function mutations in Zrt-, Irt-like protein (ZIP) 4 [5,6,7]. The clinical symptoms of AE include characteristic skin lesions, alopecia, and diarrhea

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