The individual biotin-dependent carboxylases – pyruvate, propionyl-CoA, 3-methylcrotonyl-CoA, and acetyl-CoA carboxylase – are essential for gluconeogenesis, fatty acid synthesis, and amino acid degradation, respectively.The proteolytic degradation of these holocarboxylases in the gastrointestinal tract produces biotin-containing peptides, including the significant biocytin. This is subsequently converted back into biotin by the enzyme biotinidase, which is present in almost all tissues and splits off lysine or lysil peptide. It is able to bind individual biotin molecules to histones (proteins around which DNA is wrapped) or to cleave them from histones. In this way, biotin transferase is thought to be able to affect chromatin structure (DNA’s thread scaffold), DNA repair, and gene expression. Deficiency of biotinidase – autosomal recessive inherited congenital defect, extremely rare – leads to inability to extract biotin from biocytin. Due to the increased biotin requirement, affected children depend on the supply of pharmacological amounts of free biotin. Biotin is mainly absorbed in the proximal small intestine. Because of self-synthesis in the colon by biotin-producing microorganisms, the daily excretion of biotin and its metabolites in urine and feces exceeds the amount supplied with food.
Coenzyme in carboxylation reactions
The essential function of biotin is to act as a cofactor or prosthetic group of four carboxylases that catalyze the binding of a carboxyl group (bicarbonate – CO2) inorganic acids. The B vitamin is thus involved in several essential metabolic processes of all energy-providing nutrient and vital substance groups.Biotin is a component of the following carboxylase reactions:
- Pyruvate carboxylase – important component in both gluconeogenesis and fatty acid synthesis (lipogenesis).
- Propionyl-CoA carboxylase – essential for glucose synthesis and thus for energy supply.
- 3-Methylcrotonyl-CoA carboxylase – essential for the degradation of essential amino acids (leucine catabolism).
- Acetyl-CoA carboxylase – important component in fatty acid synthesis.
Pyruvate carboxylasePyruvate carboxylase is located in the mitochondria, the “power plants” of cells. There, the enzyme is responsible for the carboxylation of pyruvate to oxaloacetate. Oxaloacetate is the starting material and thus an essential component of gluconeogenesis. The formation of new glucose takes place primarily in the liver and kidneys, and accordingly the highest activities of pyruvate carboxylase are found in these two organs. Accordingly, pyruvate carboxylase serves as a key enzyme in the new formation of glucose and is involved in the regulation of blood glucose levels. Glucose is the most important energy supplier of the organism. In particular, erythrocytes (red blood cells), brain, and renal medulla rely on glucose for energy. Following glycolysis, the metabolite acetyl-CoA is formed in the mitochondria by oxidative decarboxylation (cleavage of a carboxyl group) of pyruvate. This “activated acetic acid” (an acetic acid residue bound to a coenzyme) represents the beginning of the citrate cycluś in the mitochondria and thus the starting material for the biosynthesis of fats. In order to pass through the mitochondrial membrane, acetyl-CoA must be converted to citrate (salt of citric acid), which is permeable to the membrane. This reaction is made possible by citrate synthetase, in that the enzyme, as a result of the degradation of acetyl-CoA, transfers the acetyl residue to oxaloacetate – condensation of oxaloacetate with the formation of citrate. This reaction step of citrate cycluś releases energy, on the one hand in the form of GTP (like ATP a “universal energy grant” of the cell) and on the other hand in the form of reduction equivalents (NADH+H+ and FADH2). The latter are subsequently used in the respiratory chain to form further ATP molecules, which is the main energy gain in cellular respiration. After citrate has passed from the mitochondrion into the cytosol, it is converted back into acetyl-CoA with the help of citrate lyase.To maintain the normal activity of the citrate cycluś, oxaloacetate must be continuously produced from pyruvate by pyruvate carboxylase, which in turn is necessary for the formation of citrate.Finally, acetyl-CoA can only enter the cytosol in the form of the salt of citric acid to initiate fatty acid synthesis.Pyruvate carboxylase appears to play a crucial role as a cofactor in brain maturation due to its essential function in fatty acid synthesis (providing oxaloacetate to convert acetyl-CoA to citrate) and in the synthesis of the neurotransmitter acetylcholine. Furthermore, oxaloacetate is required for the de novo synthesis of aspartate, an excitatory (energizing) neurotransmitter. Propionyl-CoA carboxylasePropionyl-CoA carboxylase is a key enzyme localized in mitochondria in the catalysis of methylmalonyl-CoA from propionyl-CoA. In human tissues, propionic acid results from the oxidation of odd-numbered fatty acids, the degradation of certain amino acids – methionine, isoleucine, and valine – and production by microorganisms of the gastrointestinal tract.Methylmalonyl-CoA is further degraded to succinyl-CoA and oxaloacetate. Oxaloacetate results in either glucose or carbon dioxide (CO2) and water (H2O).Accordingly, propionyl-CoA carboxylase is an important component of glucose synthesis as well as energy supply. 3-Methylcrotonyl-CoA carboxylase3-methylcrotonyl-CoA carboxylase is also a mitochondrial enzyme. It is responsible for the conversion of3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA, which plays a role in the degradation of leucine. 3-Methylglutaconyl-CoA and 2-hydroxy-3-methylglutaryl-CoA are subsequently converted into acetoacetate and acetyl-CoA. The latter is an essential component of the citrate cycluś. 3-Methylcrotonyl-CoA can be degraded independently of biotin into three other compounds, which are accordingly produced more frequently in the case of biotin deficiency. Acetyl-CoA carboxylaseAcetyl-CoA carboxylase is found in both mitochondria and cytosol. The enzyme facilitates the cytosol-localized, ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. This reaction represents the beginning of fatty acid synthesis. By converting long-chain polyunsaturated fatty acids by chain elongation, malonyl-CoA is important for the formation of prostaglandin precursors. Prostaglandins belong to the group of eicosanoids (oxygenated derivatives of polyunsaturated fatty acids) that affect uterine smooth muscle function and musculature.
Other effects:
- Influence on the expression of genes of non-biotin-dependent enzymes.
- Influence on growth and maintenance of blood cells, sebaceous glands and nervous tissue.
- Influence on the immune response – by biotin supplementation of 750 µg / day for 14 days and 2 mg / day for 21 days, respectively, there was both increased expression of the genes for interleukin-1ß and interferon-y and decreased expression of the gene for interleukin-4 in blood cells; in addition, the release of various interleukins was influenced
- Biotin supplementation led to an improvement in skin texture in quite a few studies
- Daily administration of 2.5 mg biotin for 6 months was found to thicken and improve the structure of the nails