Functions of biotin
Unlike other B-vitamins, biotin itself functions as a coenzyme and is covalently bound to the enzyme proteins.
Biotin plays an essential role as a coenzyme in CO2 fixation; fatty acid synthesis, for instance, requires a biotin-containing enzyme, acetyl-CoA carboxylase, to form malonyl coenzyme A from acetyl coenzyme A.
There are several other biotin-dependent carboxylases that are important in human metabolism. Pyruvate carboxylase converts pyruvate to oxaloaceta te (OAA), a critical reaction in gluconeogenesis. Production of OAA also permits continuous feeding of acetyl CoA into the citric acid cycle and, when not needed for energy production, the citrate formed from OAA and acetyl CoA transfers the two carbons of acetyl CoA to the cytosol for fatty acid synthesis (acetyl CoA cannot penetrate the mitochondrial membrane and is regenerated from citrate in the cytosol). Propionyl CoA from the catabolism of methionine, isoleucine, and odd chain fatty acids must first be converted to methylmalonyl CoA by methylmalonyl CoA carboxylase before it is further utilized in the citric acid cycle, by means of succinyl CoA. Similarly, ,B-methylcrotonyl CoA carboxylase is essential in the catabolism of leucine.
Biotin deficiency in animals is associated with a number of metabolic alterations that cannot be directly attributed to its known enzymatic functions. Protein synthesis is reduced and appears to reflect the effect on the formation of soluble RNA. Both fasting hypoglycemia and impaired glucose tolerance have been observed in the ra t. Hypercholesterolemia has been associated with biotin deficiency in humans. Metabolic interrelationships ofbiotin with vitamin B12 folacin, and ascorbic acid have been reported but require further elucidation.
Biotin deficiency results in lassitude, anorexia, depression, malaise, muscle pain, nausea, anemia, hypercholesterolemia, and changes in the electrocardiogram. Biotin-responsive genetic conditions, which involve one or everal defective carboxylase(s), have been identified in recent years.
