Pathways

Biotin is a vitamin that is an essential nutrient for humans. Biotin can be absorbed from consuming various foods such as: legumes, soybeans, tomatoes, romaine lettuce, eggs, cow's milk, oats and many more. Biotin acts as a cofactor for enzymes to catalyze carboxylation reactions involved in gluconeogenesis, amino acid catabolism and fatty acid metabolism. Biotin deficiency has been associated with many human diseases. These diseases may be caused by dysfunctional biotin metabolism due to enzyme deficiencies. Some research suggests biotin may play a role in transcription regulation or protein expression which may lead to biotin related diseases.

Biotin (vitamin H or vitamin B7) is the essential cofactor of biotin-dependent carboxylases, such as pyruvate carboxylase and acetyl-CoA carboxylase. In E. coli and many organisms, pimelate thioester is derived from malonyl-ACP. The pathway starts with a malonyl-[acp] interacting with S-adenosylmethionine through a biotin synthesis protein BioC resulting in an S-adenosylhomocysteine and a malonyl-[acp] methyl ester. The latter compound is then involved in the synthesis of a 3-ketoglutaryl-[acp] methyl ester through a 3-oxoacyl-[acyl-carrier-protein] synthase. The compound 3-ketoglutaryl-[acp] methyl ester is reduced by a NADPH-mediated 3-oxoacyl-[acyl-carrier-protein] reductase resulting in a 3R-hydroxyglutaryl-[acp] methyl ester. It is then dehydrated through a (3R)-hydroxymyristoyl-[acp] dehydratase producing an enoylglutaryl-[acp] methyl ester. enoylglutaryl-[acp] methyl ester is then reduced through an NADPH mediated enoyl-acp-reductase [NADH] resulting in a glutaryl-[acp] methyl ester. Continuing, glutaryl-[acp] methyl ester interacts with a malonyl-[acp] through a 3-oxoacyl-[acp] synthase 2 resulting in a 3-ketopimeloyl [acp] methyl ester then is further reduced through an NADPH 3-oxoacyl [acp] reductase producing a 3-hydroxypimeloyl-[acp] methyl ester and then dehydrated by (3R)-hydroxymyristoyl-[acp] dehydratase to produce an enoylpimeloyl-[acp] methyl ester. The product is then reduced by an NADPH-dependent enoyl-[acp]reductase resulting in a pimeloyl-[acp] methyl ester. Reacting with water through a carboxylesterase, pimeloyl-[acp] methyl ester is converted into a pimeloyl-[acp] and a methanol. The pimeloyl-acp reacts with L-alanine through an 8-amino-7-oxononanoate synthase resulting in 8-amino-7-oxononanoate which in turn reacts with S-adenosylmethionine through a 7,8-diaminonanoate transaminase resulting in an S-adenosyl-4-methylthio-2-oxobutanoate and 7,8-diaminononanoate. The latter compound is then dephosphorylated through a dethiobiotin synthetase resulting in a dethiobiotin. This compound interacts with a sulfurated[sulfur carrier), a hydrogen ion, and an S-adenosylmethionine through a biotin synthase to produce biotin and releasing L-methionine and a 5-deoxyadenosine. Finally, biotin is then metabolized by a bifunctional protein resulting in pyrophosphate and biotinyl-5-AMP which in turn reacts with the same protein (bifunctional protein birA resulting in a biotin carboxyl carrying protein. This product then enters fatty acid biosynthesis.

Biotin (vitamin H or vitamin B7) is the essential cofactor of biotin-dependent carboxylases, such as pyruvate carboxylase and acetyl-CoA carboxylase. In E. coli and many organisms, pimelate thioester is derived from malonyl-ACP. The pathway starts with a malonyl-[acp] interacting with S-adenosylmethionine through a biotin synthesis protein BioC resulting in an S-adenosylhomocysteine and a malonyl-[acp] methyl ester. The latter compound is then involved in the synthesis of a 3-ketoglutaryl-[acp] methyl ester through a 3-oxoacyl-[acyl-carrier-protein] synthase. The compound 3-ketoglutaryl-[acp] methyl ester is reduced by a NADPH-mediated 3-oxoacyl-[acyl-carrier-protein] reductase resulting in a 3R-hydroxyglutaryl-[acp] methyl ester. It is then dehydrated through a (3R)-hydroxymyristoyl-[acp] dehydratase producing an enoylglutaryl-[acp] methyl ester. enoylglutaryl-[acp] methyl ester is then reduced through an NADPH mediated enoyl-acp-reductase [NADH] resulting in a glutaryl-[acp] methyl ester. Continuing, glutaryl-[acp] methyl ester interacts with a malonyl-[acp] through a 3-oxoacyl-[acp] synthase 2 resulting in a 3-ketopimeloyl [acp] methyl ester then is further reduced through an NADPH 3-oxoacyl [acp] reductase producing a 3-hydroxypimeloyl-[acp] methyl ester and then dehydrated by (3R)-hydroxymyristoyl-[acp] dehydratase to produce an enoylpimeloyl-[acp] methyl ester. The product is then reduced by an NADPH-dependent enoyl-[acp]reductase resulting in a pimeloyl-[acp] methyl ester. Reacting with water through a carboxylesterase, pimeloyl-[acp] methyl ester is converted into a pimeloyl-[acp] and a methanol. The pimeloyl-acp reacts with L-alanine through an 8-amino-7-oxononanoate synthase resulting in 8-amino-7-oxononanoate which in turn reacts with S-adenosylmethionine through a 7,8-diaminonanoate transaminase resulting in an S-adenosyl-4-methylthio-2-oxobutanoate and 7,8-diaminononanoate. The latter compound is then dephosphorylated through a dethiobiotin synthetase resulting in a dethiobiotin. This compound interacts with a sulfurated[sulfur carrier), a hydrogen ion, and an S-adenosylmethionine through a biotin synthase to produce biotin and releasing L-methionine and a 5-deoxyadenosine. Finally, biotin is then metabolized by a bifunctional protein resulting in pyrophosphate and biotinyl-5-AMP which in turn reacts with the same protein (bifunctional protein birA resulting in a biotin carboxyl carrying protein. This product then enters fatty acid biosynthesis.

Biotin is an essential vitamin, which most plants such as Arabidopsis thaliana is capable of synthesizing on its own. Biotin also takes place in numerous carboxylation, decarboxylation and transcarboxylation reactions acting as a cofactor to transfer carbon dioxide to its respective place. Biotin transporters are vital to the regulation of biotin needs in plant cells as it plays a role in its continued use and synthesis within the plant. A.thaliana synthesis of biotin is required to help supplement heterotrophs (that cannot synthesize biotin on their own) such as humans, as it aids in many metabolic processes.

The assembly of a biotin-carboxyl carrier protein starts with a biotin carboxyl carrier protein monomer interacting with an ATP, and a biotin through a biotin -acetyl-coa-carboxylase ligase resulting in the release of a hydrogen ion, an AMP, a diphosphate and a biotynylated BCCP monomer. The latter compound reacts spontaneously to create a biotinylated BCCP dimer. This compound in turn reacts with a hydrogen carbonate and an ATP driven biotin carboxylase resulting in the release of ADP, a hydrogen Ion , a phosphate and a carboxylated biotinylated BCCP dimer. This complex can be degraded by reacting with water, an acetyl0CoA, and an ATP driven acetyl-CoA carboxyltransferase resulting in the release of a hydrogen ion, a phosphate, an ADP, a malonyl-CoA and a biotynylated BCCP dimer

The assembly of a biotin-carboxyl carrier protein starts with a biotin carboxyl carrier protein monomer interacting with an ATP, and a biotin through a biotin -acetyl-coa-carboxylase ligase resulting in the release of a hydrogen ion, an AMP, a diphosphate and a biotynylated BCCP monomer. The latter compound reacts spontaneously to create a biotinylated BCCP dimer. This compound in turn reacts with a hydrogen carbonate and an ATP driven biotin carboxylase resulting in the release of ADP, a hydrogen Ion , a phosphate and a carboxylated biotinylated BCCP dimer. This complex can be degraded by reacting with water, an acetyl0CoA, and an ATP driven acetyl-CoA carboxyltransferase resulting in the release of a hydrogen ion, a phosphate, an ADP, a malonyl-CoA and a biotynylated BCCP dimer

Biotinidase deficiency (Multiple carboxylase deficiency) is an autosomal recessive disease caused by a mutation in the BTD gene which codes for biotinidase. A deficiency in this enzyme results in accumulation of ammonia and ketone bodies in blood; 3-hydroxyisovaleric acid in plasma, spinal fluid, and urine; hydroxypropionic acid, 2-hydroxybutyric acid, 3-Hydroxybutyric acid, and citric acid in spinal fluid; and 3-methylcrotonylglycine, hydroxypropionic acid, and L and D-lactic acid in urine. Symptoms, which can present from birth into adulthood include hypotonia, ketosis, hyperammonemia, motor retardation, coma, and seborrhoic skin rash. Treatment includes biotin.

Biotinidase deficiency (Multiple carboxylase deficiency) is an autosomal recessive disease caused by a mutation in the BTD gene which codes for biotinidase. A deficiency in this enzyme results in accumulation of ammonia and ketone bodies in blood; 3-hydroxyisovaleric acid in plasma, spinal fluid, and urine; hydroxypropionic acid, 2-hydroxybutyric acid, 3-Hydroxybutyric acid, and citric acid in spinal fluid; and 3-methylcrotonylglycine, hydroxypropionic acid, and L and D-lactic acid in urine. Symptoms, which can present from birth into adulthood include hypotonia, ketosis, hyperammonemia, motor retardation, coma, and seborrhoic skin rash. Treatment includes biotin.

Biotinidase deficiency (Multiple carboxylase deficiency) is an autosomal recessive disease caused by a mutation in the BTD gene which codes for biotinidase. A deficiency in this enzyme results in accumulation of ammonia and ketone bodies in blood; 3-hydroxyisovaleric acid in plasma, spinal fluid, and urine; hydroxypropionic acid, 2-hydroxybutyric acid, 3-Hydroxybutyric acid, and citric acid in spinal fluid; and 3-methylcrotonylglycine, hydroxypropionic acid, and L and D-lactic acid in urine. Symptoms, which can present from birth into adulthood include hypotonia, ketosis, hyperammonemia, motor retardation, coma, and seborrhoic skin rash. Treatment includes biotin.

Biotinidase deficiency (Multiple carboxylase deficiency) is an autosomal recessive disease caused by a mutation in the BTD gene which codes for biotinidase. A deficiency in this enzyme results in accumulation of ammonia and ketone bodies in blood; 3-hydroxyisovaleric acid in plasma, spinal fluid, and urine; hydroxypropionic acid, 2-hydroxybutyric acid, 3-Hydroxybutyric acid, and citric acid in spinal fluid; and 3-methylcrotonylglycine, hydroxypropionic acid, and L and D-lactic acid in urine. Symptoms, which can present from birth into adulthood include hypotonia, ketosis, hyperammonemia, motor retardation, coma, and seborrhoic skin rash. Treatment includes biotin.