Reactome: A Curated Pathway Database

Defects in biotin (Btn) metabolism (R-HSA-3323169)

Species Homo sapiens


Biotin (Btn, vitamin B7, vitamin H, coenzyme R) is an essential cofactor for five biotin-dependent carboxylase enzymes, involved in the synthesis of fatty acids, isoleucine, valine and in gluconeogenesis. Thus, Btn is necessary for cell growth, fatty acid synthesis and the metabolism of fats and amino acids. Inherited metabolic disorders characterized by deficient activities of all five biotin dependent carboxylases are termed multiple carboxylase deficiencies. Two congenital defects in biotin metabolism leading to multiple carboxylase deficiency are known, holocarboxylase synthetase deficiency (MIM 609018) and biotinidase deficiency (MIM 253260). In both scenarios symptoms include ketolactic acidosis, organic aciduria, hyperammonemia, skin rashes, hypotonia, seizures, developmental delay, alopecia, and coma. As humans are auxotrophic for Btn, the micronutrient must be obtained from external soures such as intestinal microflora and dietary forms. Accordingly, severe malnutrition can also give rise to biotin deficiency and multiple carboxylase deficiency. Biotin deficiency can also be induced by the excessive consumption of raw egg white that contains the biotin-binding protein avidin. Holocarboxylase synthetase deficiency arises when all five biotin-dependent enzymes are not biotinylated leading to their reduced activities. The defective genes causing these conditions are described here (Pendini et al. 2008, Suzuki et al. 2005). Biotinidase deficiency is caused by defects in the recycling of Btn. General symptoms include decreased appetite and growth, dermatitis and perosis. The defective genes causing these conditions are described here (Procter et al. 2013).

Locations in the PathwayBrowser
Name Identifier Synonyms
vitamin metabolic disorder 0050718
Literature References
pubMedId Title Journal Year
18442489 Microbial biotin protein ligases aid in understanding holocarboxylase synthetase deficiency Biochim. Biophys. Acta 2008
16134170 Mutations in the holocarboxylase synthetase gene HLCS Hum. Mutat. 2005
23550138 The Biotinidase Gene Variants Registry: A Paradigm Public Database G3 (Bethesda) 2013