Avidin biotin deficiency

Biotin binds with high af nity (/Cd = 10 M) and specificity to avidin, a protein found in egg white. Since boiling denatures avidin, biotin deficiency only occurs when egg whites are eaten raw. 

Alimentary biotin deficiency is rare. It may, however, occur in patients on long-term parenteral nutrition lacking biotin or in persons who frequently consume raw egg white. Raw egg white contains a biotin-binding glycoprotein, called avidin, which renders biotin biologically unavailable. Pharmacological doses of the vitamin (1-10 mg/d) are then used to treat deficiency symptoms. There are no reports of toxicity for daily oral doses up to 200 mg and daily intravenous doses of up to 20 mg [2]. 

The physiologic sequelae of biotin deficiency are almost unexplored. Severe skin lesions, especially seborrheic dermatitis and Leiner s disease (Erythroderma desquamativum or exfoliative dermatitis), were increased in young infants bom of mothers on a restricted diet low in eggs, livers, and other biotin-rich foods. After biotin administration the lesions healed. There are claims that excess biotin produces a fatty liver characterized by heightened cholesterol content. Choline has no effect in the prevention of biotin-fatty livers (G2, M2). In mice with transplanted tumors, both the tumors and the blood levels of biotin are below normal (R8). More recent studies established a protection with avidin, the biotin-binding fraction of egg white, against tumor formation (K4). More data along these lines are still needed for confirmation. 

Biotin deficiency is characterized by anorexia, nausea, vomiting, glossitis, depression, and dry, scaly dermatitis. Biotin deficiency occurs when avidin, a biotinbinding glycoprotein, is present. Avidin, which is found in raw egg whites, binds the biotin, making it nutritionally unavailable. 

Biotin deficiency can be triggered only experimentally, using diets rich in raw egg white. The latter contains avidin, a 70 kD protein that binds biotin in an inactive form. The deficiency leads to dermatitis and hair loss in rats. 

Acquired biotin deficiency is extremely rare but may occur in special conditions such as long-term parenteral nutrition without biotin supplementation, short bowel syndrome and after excessive intake of raw egg white, which contains the potent bio-tin-binding protein avidin. The main symptoms are alopecia and skin abnormalities which resolve after administration of biotin [2, 30]. 

Biotin deficiency is rare but under laboratory conditions it can be induced by feeding subjects with large amounts of raw egg white which contains the protein, avidin, which has a binding site for the imidazole moiety of biotin, thus making it unavailable. Avidin is denatured by heat and, therefore, biotin binding occurs only in raw egg albumen. Symptoms of biotin deficiency include scaly dermatitis, hair loss, loss of appetite, nausea, hallucinations and depression. 

Rare — None Consumption of large amounts of raw egg whites (which contains e protein, avidin, that binds biotin) can induce a biotin deficiency... 

Biotin required for growth and normal function by animals, yeast, and many bacteria is seldom found in deficiency in humans because the intestinal bacteria synthesize it in sufficient quantity to meet requirements. Biotin deficiency does occur, however, 111 animals fed raw whiles of eggs. The egg white contains a protein, avidin, which combines with biotin, and tins complex is not broken down by enzymes of the gastrointestinal tract. Hence, a deficiency develops. 

A mouse can be made biotin deficient by feeding the animal food lacking biotin and supplemented with the egg white protein avidin, which strongly binds biotin, for 8 weeks. If the animal is then given radiola-... 

Research on avidin and biotin (vitamin H) developed from nutritional studies focused on understanding why rats fed large quantities of egg whites developed malnutrition. Subsequently, biotin was found to prevent this malnutrition and in 1975, Green [12] isolated the protein, avidin, in egg whites that was responsible for the biotin deficiency. In egg whites avidin serves as an... 

Fig. 5 Metabolic blocks caused by biotin deficiencies. There are a small number of proteins that are biotinylated in vivo. Note that the naturally occurring biotin and biotinylated proteins may interfere with applications that use strept(avidin) on biological samples...

The original interest in avidin was because of the egg white injury that was subsequently shown to be avidin-induced biotin deficiency. Thereafter, avidin was used because of its high affinity for biotin (a dissociation constant of 10 mol per L), not only to induce experimental biotin deficiency, but also to bind to biotin in isolated enzymes and thus, by irreversible inhibition, demonstrate the coenzyme role of biotin. Because of the stability of the avidin-biotin complex, it has not been possible to use immobilized avidin as a means of purifying biotin enzymes - there seems to be no way in which the enzyme can be released from avidin binding. Because of its high affinity for biotin, avidin is used to provide an extremely sensitive system for linking reporter molecules in a variety of analytical systems. 

Both avidin and the avidin-biotin complex are very stable to heat. To release biotin from avidin binding, autoclaving above 130°C is required, and free avidin is stable up to about 85°C. Avidin is also resistant to proteolysis and, as is obvious from the use of raw egg white diets to induce biotin deficiency, biotin cannot be released from avidin binding in the gastrointestinal tract. Lysosomal hydrolases do release biotin from avidin binding, and intravenously administered avidin-biotin can be a source of biotin. 

It influences fat metabolism, decarboxylation and carbon dioxide fixation, and deamination of some amino acids. It is closely related metabolically to pantothenic acid and folic acid. A biotin deficiency may be induced by ingestion of avidin, a raw-egg protein, because of the formation of a nonabsorbable biotin-avidin complex. Biotin is synthesized in the intestinal tract of humans therefore, normally it is not essential in the diet. 

Biotin Deficiency. Relative to many of the vitamins, it is easy to induce a biotin deficiency by feeding volunteers raw egg white. Avidin, a basic protein found in egg white, forms salt linkages with acidic biotin and prevent its transport across the intestinal barrier. Cooked egg white is not a problem. Because biotin is found in the yolk, eating whole raw egg will not induce a deficiency. Deficiencies also were caused in patients on total parenteral nutrition (TPN) because biotin was not included in the early formulations. Symptoms include dermatitis, loss of hair color, and central neurological effects. 

Biotin deficiency occurs when large amounts of raw egg white are consumed. Egg white contains avidin, a protein (M.W. 70,000) that binds biotin strongly and specifically, preventing its absorption from the intestine. Because of the tight binding and specificity of biotin, avidin-labeled probes have been used to detect proteins and nucleic acids to which biotin has been covalently attached ( biotinylated molecules). Avidin is a homotetramer. Each subunit contains 128 amino acids and binds one molecule of biotin. The affinity of avidin for biotin is abolished by heat and other denaturants. Biotin deficiency can result from sterilization of the intestine by antibiotics and from administration of biotin analogues. 

Biotin (vitamin H) is an unusual vitamin because it can be synthesized by bacteria that live in the intestine. Consequently, biotin does not have to be included in our diet and deficiencies are rare. Biotin deficiencies, however, can be found in people who maintain a diet high in raw eggs. Egg whites contain a protein (avidin) that binds biotin tightly and thereby prevents it from acting as a coenzyme. When eggs are cooked, avidin is denatured, and the denatured protein does not bind biotin. Biotin is attached to its enzyme by forming an amide with the amino group of a lysine side chain. 

Biotin is a vitamin. A deficiency of biotin is very rare in humans because it is required in such small amounts and is synthesized by intestinal bacteria. However, an interesting case of biotin deficiency arose in a man eating a diet composed principally of peanuts and raw egg whites. Egg whites contain a biotin binding protein, avidin. Since he did not denature avidin by cooking the egg whites, it depleted his diet of biotin. 

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