Biotin

Biotin

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Encyclopedia
Biotin, also known as Vitamin H or Coenzyme R, is a water-soluble B-complex vitamin
B vitamins
B vitamins are a group of water-soluble vitamins that play important roles in cell metabolism. The B vitamins were once thought to be a single vitamin, referred to as vitamin B . Later research showed that they are chemically distinct vitamins that often coexist in the same foods...

 (vitamin B7) discovered by Bateman
Bateman
-People:*Ahmad Bateman , professional golfer*Brian Bateman , professional golfer*Charles Bateman , architect*C. Donald Bateman, inventor and inductee on the National Inventors Hall of Fame...

 in 1916. It is composed of a ureido (tetrahydroimidizalone) ring fused with a tetrahydrothiophene
Tetrahydrothiophene
Tetrahydrothiophene is a heterocyclic organic compound consisting of a five-membered ring containing four carbon atoms and a sulfur atom. It is the saturated analog of thiophene. It is a volatile, clear, colorless liquid with a strong unpleasant odor....

 ring. A valeric acid
Valeric acid
Valeric acid, or pentanoic acid, is a straight-chain alkyl carboxylic acid with the chemical formula C5H10O2. Like other low-molecular-weight carboxylic acids, it has a very unpleasant odor. It is found naturally in the perennial flowering plant valerian , from which it gets its name. Its...

 substituent is attached to one of the carbon atoms of the tetrahydrothiophene ring. Biotin is a coenzyme in the metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 of fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...

s, isoleucine
Isoleucine
Isoleucine is an α-amino acid with the chemical formula HO2CCHCHCH2CH3. It is an essential amino acid, which means that humans cannot synthesize it, so it must be ingested. Its codons are AUU, AUC and AUA....

, and valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...

, and it plays a role in gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

.

General overview


Biotin is necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids. It plays a role in the citric acid cycle
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...

, which is the process by which biochemical energy is generated during aerobic respiration
Cellular respiration
Cellular respiration is the set of the metabolic reactions and processes that take place in the cells of organisms to convert biochemical energy from nutrients into adenosine triphosphate , and then release waste products. The reactions involved in respiration are catabolic reactions that involve...

. Biotin not only assists in various metabolic reactions but also helps to transfer carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

. Biotin may also be helpful in maintaining a steady blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...

 level. Biotin is often recommended for strengthening hair and nails. As a consequence, it is found in many cosmetics and health products for the hair and skin, though it cannot be absorbed through the hair or skin itself.

Biotin deficiency is rare because, in general, intestinal bacteria produce biotin in excess of the body's daily requirements. For that reason, statutory agencies in many countries, for example the USA and Australia, do not prescribe a recommended daily intake of biotin. However, a number of metabolic disorders in which an individual's metabolism of biotin is abnormal exist.

Biosynthesis


The Empirical formula
Empirical formula
In chemistry, the empirical formula of a chemical compound is the simplest positive integer ratio of atoms of each element present in a compound. An empirical formula makes no reference to isomerism, structure, or absolute number of atoms. The empirical formula is used as standard for most ionic...

 of Biotin is (C10 H16 O3 N2 S). Biotin has an unusual structure. It has two side rings fused together. The two side rings are imidazole
Imidazole
Imidazole is an organic compound with the formula C3H4N2. This aromatic heterocyclic is a diazole and is classified as an alkaloid. Imidazole refers to the parent compound, whereas imidazoles are a class of heterocycles with similar ring structure, but varying substituents...

 and thiophene
Thiophene
Thiophene is a heterocyclic compound with the formula C4H4S. Consisting of a flat five-membered ring, it is aromatic as indicated by its extensive substitution reactions. Related to thiophene are benzothiophene and dibenzothiophene, containing the thiophene ring fused with one and two benzene...

. Biotin is a heterocyclic S-containing (mono-)carboxylic acid
Carboxylic acid
Carboxylic acids are organic acids characterized by the presence of at least one carboxyl group. The general formula of a carboxylic acid is R-COOH, where R is some monovalent functional group...

. Biotin is made from two precursors, alanine and pimeloyl-CoA via three enzymes. 8-Amino-7-oxopelargonic acid synthase is a pyridoxal 5'-phosphate enzyme. The pimeloyl-CoA, could be produced by a modified fatty acid pathway involving a malonyl thioester as the starter. 7,8-Diaminopelargonic acid (DAPA) aminotransferase, is unusual in using S-adenosylmethionine (AdoMet) as the NH2 donor. Dethiobiotin synthethase catalyzes the formation of the ureido ring via a DAPA carbamate activated with ATP. Biotin synthase reductively cleaves AdoMet into a deoxyadenosyl radical -- a first radical formed on dethiobiotin is trapped by the sulfur donor, which was found to be the iron-sulfur (Fe-S) center contained in the enzyme.

Cofactor Biochemistry


Biotin D(+) is a cofactor
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....

 responsible for carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...

 transfer in several carboxylase enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

s:
  • Acetyl-CoA carboxylase alpha
    Acetyl-CoA carboxylase
    Acetyl-CoA carboxylase is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase and carboxyltransferase...

  • Acetyl-CoA carboxylase beta
    Acetyl-CoA carboxylase
    Acetyl-CoA carboxylase is a biotin-dependent enzyme that catalyzes the irreversible carboxylation of acetyl-CoA to produce malonyl-CoA through its two catalytic activities, biotin carboxylase and carboxyltransferase...

  • Methylcrotonyl-CoA carboxylase
    Methylcrotonyl-CoA carboxylase
    Methylcrotonyl CoA carboxylase is a biotin-requiring enzyme located in the mitochondria...

  • Propionyl-CoA carboxylase
    Propionyl-CoA carboxylase
    Propionyl-CoA carboxylase catalyses the carboxylation reaction of propionyl CoA in the mitochondrial matrix. The enzyme is biotin dependent. The product of the reaction is -methylmalonyl CoA. Propionyl CoA is the end product of metabolism of odd-chain fatty acids, and is also a metabolite of most...

  • Pyruvate carboxylase
    Pyruvate carboxylase
    Pyruvate carboxylase is an enzyme of the ligase class that catalyzes the irreversible carboxylation of pyruvate to form oxaloacetate .It is an important anaplerotic reaction that creates oxaloacetate from pyruvate...



and, so, is important in fatty acid synthesis
Fatty acid synthesis
Fatty acid synthesis is the creation of fatty acids from acetyl-CoA and malonyl-CoA precursors through action of enzymes called fatty acid synthases...

, branched-chain amino acid catabolism, and gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

. Biotin covalently attaches to the epsilon-amino group of specific lysine residues in these carboxylases. This biotinylation
Biotinylation
In biochemistry, biotinylation is the process of covalently attaching biotin to a protein, nucleic acid or other molecule. Biotinylation is rapid, specific and is unlikely to perturb the natural function of the molecule due to the small size of biotin...

 reaction requires ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...

 and is catalyzed by holocarboxylase synthetase. The attachment of biotin to various chemical sites can be used as an important laboratory technique to study various processes including protein localization, protein interactions
Protein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...

, DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

, and replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

. Biotinidase itself is known to be able to biotinylate histone proteins
Histone
In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes. They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation...

, but little biotin is found naturally attached to chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

.

Biotin binds very tightly to the tetrameric protein avidin
Avidin
Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians deposited in the whites of their eggs. In chicken egg white, avidin makes up approximately 0.05% of total protein...

 (also streptavidin
Streptavidin
Streptavidin is a 60000 dalton protein purified from the bacterium Streptomyces avidinii. Streptavidin homo-tetramers have an extraordinarily high affinity for biotin . With a dissociation constant on the order of ≈10-14 mol/L, the binding of biotin to streptavidin is one of the strongest...

 and neutravidin
NeutrAvidin
NeutrAvidin protein is a deglycosylated version of avidin, with a mass of approximately 60,000 daltons. As a result of carbohydrate removal, lectin binding is reduced to undetectable levels, yet biotin binding affinity is retained because the carbohydrate is not necessary for this activity...

), with a dissociation constant
Dissociation constant
In chemistry, biochemistry, and pharmacology, a dissociation constant is a specific type of equilibrium constant that measures the propensity of a larger object to separate reversibly into smaller components, as when a complex falls apart into its component molecules, or when a salt splits up into...

 Kd in the order of 10−15, which is one of the strongest known protein-ligand interactions, approaching the covalent bond in strength. This is often used in different biotechnological applications. Until 2005, very harsh conditions were thought to be required to break the biotin-streptavidin bond.

Sources of biotin


Biotin is consumed from a wide range of food sources in the diet, however there are few particularly rich sources. Foods with a relatively high biotin content include Swiss chard, raw egg yolk (however, the consumption of egg whites with egg yolks minimizes the effectiveness of egg yolk's biotin in one's body), liver, some vegetables, and peanuts. The dietary biotin intake in Western populations has been estimated to be 35 to 70 μg/d (143–287 nmol/d).

Biotin is also available from supplements. The synthetic process developed by Leo Sternbach
Leo Sternbach
Leo Henryk Sternbach was a Polish-Jewish chemist who is credited with discovering benzodiazepines, main class of tranquilizers.-Biography:...

 and Moses Wolf Goldberg
Moses Wolf Goldberg
Dr Moses Wolf Goldberg was an Estonian-Jewish chemist who, along with Leo Henryk Sternbach, developed a process for the synthesis of biotin in 1949.-Biography:...

 in the 1940s uses fumaric acid
Fumaric acid
Fumaric acid or trans-butenedioic acid is the chemical compound with the formula HO2CCH=CHCO2H. This white crystalline compound is one of two isomeric unsaturated dicarboxylic acids, the other being maleic acid. In fumaric acid the carboxylic acid groups are trans and in maleic acid they are cis...

 as a starting material.

Bioavailability


Biotin is also called vitamin H (the H represents "Haar und Haut”, German words for “hair and skin”) or vitamin B7. Studies on the bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...

 of biotin have been conducted in rats and in chicks. From these studies, it was concluded that biotin bioavailability may be low or variable, depending on the type of food being consumed. In general, biotin exists in food as protein bound form or biocytin
Biocytin
Biocytin is a chemical compound that is an amide formed from the vitamin biotin and the amino acid L-lysine. As an intermediate in the metabolism of biotin, biocytin occurs naturally in blood serum and urine....

. Proteolysis by protease is required prior to absorption. This process assists free biotin release from biocytin and protein-bound biotin. The biotin present in corn is readily available; however, most grains have about a 20-40% bioavailability of biotin.

A possible explanation for the wide variability in biotin bioavailability is that it is due to ability of an organism to break various biotin-protein bonds from food. Whether an organism has an enzyme with the ability to break that bond will determine the bioavailability of biotin from the foodstuff.

Factors that affect biotin requirements


The frequency of marginal biotin status is not known, but the incidence of low circulating biotin levels in alcoholics has been found to be much greater than in the general population. Also, relatively low levels of biotin have been reported in the urine or plasma of patients that have had partial gastrectomy
Gastrectomy
A gastrectomy is a partial or full surgical removal of the stomach.-Indications:Gastrectomies are performed to treat cancer and perforations of the stomach wall....

 or that have other causes of achlorhydria
Achlorhydria
Achlorhydria or hypochlorhydria refers to states where the production of gastric acid in the stomach is absent or low, respectively. It is associated with various other medical problems.-Signs and symptoms:...

, burn patients, epileptics, elderly individuals, and athletes. Pregnancy and lactation
Lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...

 may be associated with an increased demand for biotin. In pregnancy, this may be due to a possible acceleration of biotin catabolism
Catabolism
Catabolism is the set of metabolic pathways that break down molecules into smaller units and release energy. In catabolism, large molecules such as polysaccharides, lipids, nucleic acids and proteins are broken down into smaller units such as monosaccharides, fatty acids, nucleotides, and amino...

, whereas, in lactation, the higher demand has yet to be elucidated. Recent studies have shown that marginal biotin deficiency can be present in human gestation, as evidenced by increased urinary excretion of 3-hydroxyisovaleric acid, decreased urinary excretion of biotin and bisnorbiotin, and decreased plasma concentration of biotin. Additionally, smoking may further accelerate biotin catabolism in women.

Deficiency


Biotin deficiency
Biotin deficiency
Biotin deficiency is a rare nutritional disorder which can become serious, even fatal, if allowed to progress untreated. It can occur in people of any age, ancestry, or gender...

 is relatively rare and mild, and can be addressed with supplementation. Such deficiency can be caused by the consumption of raw egg white
Egg white
Egg white is the common name for the clear liquid contained within an egg. In chickens it is formed from the layers of secretions of the anterior section of the hen's oviduct during the passage of the egg. It forms around either fertilized or unfertilized egg yolks...

s (eating two or more uncooked egg whites daily for several months has caused biotin deficiency that is serious enough to produce symptoms http://www.nlm.nih.gov/medlineplus/druginfo/natural/313.html), which contain high levels of the protein avidin
Avidin
Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians deposited in the whites of their eggs. In chicken egg white, avidin makes up approximately 0.05% of total protein...

, which binds biotin strongly.

The first demonstration of biotin deficiency in animals was observed in animals fed raw egg white. Rats fed egg white protein were found to develop dermatitis, hair loss, alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...

, and neuromuscular dysfunction. This syndrome was called egg white injury and was discovered to be caused by a glycoprotein found in egg white called avidin.

Avidin denaturates upon heating (cooking), while the biotin remains intact.

Symptoms of biotin deficiency include:
  • Hair loss (alopecia
    Alopecia
    Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...

    )
  • Conjunctivitis
    Conjunctivitis
    Conjunctivitis refers to inflammation of the conjunctiva...

  • Dermatitis
    Dermatitis
    -Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...

     in the form of a scaly red rash around the eyes, nose, mouth, and genital area.
  • Neurological symptoms in adults such as depression, lethargy, hallucination, and numbness and tingling of the extremities.


The characteristic facial rash, together with an unusual facial fat distribution, has been termed the "biotin-deficient face" by some experts. Individuals with hereditary disorders of biotin deficiency have evidence of impaired immune system function, including increased susceptibility to bacterial and fungal infections.

Pregnant women tend to have a high risk of biotin deficiency. Research has shown that nearly half of pregnant women have an abnormal increase of 3-hydroxyisovaleric acid, which reflects reduced status of biotin. Numbers of studies reported that this possible biotin deficiency during the pregnancy may cause infants' congenital malformations such as cleft palate. Mice fed with dried raw egg to induce biotin deficiency during the gestation resulted in up to 100% incidence of the infants' malnourishment. Infants and embryos are more sensitive to the biotin deficiency. Therefore, even a mild level of the mother's biotin deficiency that does not reach the appearance of physiological deficiency signs may cause a serious consequence in the infants.

Metabolic disorders


Inherited metabolic disorders characterized by deficient activities of biotin-dependent carboxylases are termed multiple carboxylase deficiency
Multiple carboxylase deficiency
Multiple carboxylase deficiency is a form of metabolic disorder involving failures of carboxylation enzymes.The deficiency can be in biotinidase or holocarboxylase synthetase.These conditions respond to biotin.Forms include:...

. These include deficiencies in the enzymes holocarboxylase synthetase or biotinidase
Biotinidase
Biotinidase also known as BTD is an enzyme that in humans is encoded by the BTD gene.- Function :This enzyme allows the body to use and to recycle the B vitamin biotin, sometimes called vitamin H. Biotinidase extracts biotin from food because the body needs biotin in its free, unattached form...

. Holocarboxylase synthetase deficiency
Holocarboxylase synthetase deficiency
Holocarboxylase synthetase deficiency is an inherited metabolic disorder in which the body is unable to use the vitamin biotin effectively. This disorder is classified as a multiple carboxylase deficiency, a group of disorders characterized by impaired activity of certain enzymes that depend on...

 prevents the body's cells from using biotin effectively, and thus interferes with multiple carboxylase reactions. Biochemical and clinical manifestation includes: ketolactic acidosis, organic aciduria, hyperammonemia
Hyperammonemia
Hyperammonemia is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to encephalopathy and death. It may be primary or secondary....

, skin rash, feeding problems, hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...

, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

s, developmental delay, alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...

, and coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...

.

Biotinidase deficiency
Biotinidase deficiency
Biotinidase deficiency is an autosomal recessive metabolic disorder in which biotin is not released from proteins in the diet during digestion or from normal protein turnover in the cell. This situation results in biotin deficiency....

 is not due to inadequate biotin, but rather to a deficiency in the enzymes that process it. Biotinidase
Biotinidase
Biotinidase also known as BTD is an enzyme that in humans is encoded by the BTD gene.- Function :This enzyme allows the body to use and to recycle the B vitamin biotin, sometimes called vitamin H. Biotinidase extracts biotin from food because the body needs biotin in its free, unattached form...

 catalyzes the cleavage of biotin from biocytin and biotinyl-peptides (the proteolytic degradation products of each holocarboxylase) and thereby recycles biotin. It is also important in freeing biotin from dietary protein-bound biotin. General symptoms include decreased appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...

 and growth
Growth
Growth refers to an increase in some quantity over time.The quantity can be:*Physical *Abstract ....

. Dermatologic symptoms include dermatitis
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...

, alopecia
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...

 (hair loss) and achromotrichia (absence or loss of pigment in the hair). Perosis (a shortening and thickening of bones) is seen in the skeleton. Fatty liver and kidney syndrome (FLKS) and hepatic steatosis also can occur.

Diabetes


Diabetics may benefit from biotin supplementation. In both insulin-dependent and non-insulin-dependent diabetics, supplementation with biotin can improve blood sugar control and help lower fasting blood glucose levels, in some studies the reduction in fasting glucose exceeded 50 percent. Biotin can also play a role in preventing the neuropathy often associated with diabetes, reducing both the numbness and tingling associated with poor glucose control.

Hair & nail problems


The signs and symptoms of biotin deficiency include hair loss which progresses in severity to include loss of eyelashes and eyebrows in severely deficient subjects, as well as nails that break, chip, or flake easily. Biotin supplements are available in most pharmacies. The recommended dose is about 5000mcg to 7500mcg per day. Thicker and stronger hair and healthier nails may be seen within several months, depending on rate of growth. Some shampoos are available that contain biotin, but it is doubtful whether they would have any useful effect, as biotin is not absorbed well through the skin.

Palmo Plantar Pustulosis


Patients with palmoplantar pustulosis had metabolic derangements of glucose and fatty acids as well as immune dysfunction derived from biotin deficiency, which led to abnormal manifestations of skin, bone and other tissues and organs. All of the clinical, metabolic and immune disorders were improved by biotin administration. These findings indicate that biotin deficiency was implicated in the outbreak and exacerbation of the disease and its complications. Supplementary addition of a probiotic agent to the biotin treatment intensified the therapeutic effect of the vitamin. Additionally, patients with psoriasis vulgaris, systemic lupus erythematosus
Systemic lupus erythematosus
Systemic lupus erythematosus , often abbreviated to SLE or lupus, is a systemic autoimmune disease that can affect any part of the body. As occurs in other autoimmune diseases, the immune system attacks the body's cells and tissue, resulting in inflammation and tissue damage...

, atopic dermatitis
Atopic dermatitis
Atopic dermatitis is an inflammatory, chronically relapsing, non-contagious and pruritic skin disorder...

 or rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

 also had biotin deficiency with the subsequent metabolic abnormalities and immune dysfunction, and so the biotin treatment provided beneficial effects in the therapy of the diseases, as in the case of palmoplantar pustulosis
Pustulosis
Pustulosis is highly inflammatory skin condition resulting in large fluid-filled blister-like areas - pustules. Pustulosis typically occurs on the palms of the hands and/or the soles of the feet. The skin of these areas peels and flakes ....

.

Cradle cap (seborrheic dermatitis)


Children with a rare inherited metabolic disorder called phenylketonuria
Phenylketonuria
Phenylketonuria is an autosomal recessive metabolic genetic disorder characterized by a mutation in the gene for the hepatic enzyme phenylalanine hydroxylase , rendering it nonfunctional. This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine...

 (PKU; in which one is unable to break down the amino acid phenylalanine) often develop skin conditions such as eczema
Eczema
Eczema is a form of dermatitis, or inflammation of the epidermis . In England, an estimated 5.7 million or about one in every nine people have been diagnosed with the disease by a clinician at some point in their lives.The term eczema is broadly applied to a range of persistent skin conditions...

 and seborrheic dermatitis in areas of the body other than the scalp. The scaly skin changes that occur in people with PKU may be related to poor ability to use biotin. Increasing dietary biotin has been known to improve seborrheic dermatitis in these cases.

Toxicity


Animal studies have indicated few, if any, effects due to high level doses of biotin. This may provide evidence that both animals and humans could tolerate doses of at least an order of magnitude greater than each of their nutritional requirements. There are no reported cases of adverse effects from receiving high doses of the vitamin, in particular, when used in the treatment of metabolic disorders causing sebhorrheic dermatitis
Dermatitis
-Etymology:Dermatitis derives from Greek derma "skin" + -itis "inflammation" and genetic disorder.-Terminology:There are several different types of dermatitis. The different kinds usually have in common an allergic reaction to specific allergens. The term may describe eczema, which is also called...

 in infants.

Laboratory uses


In the laboratory, biotin is often chemically linked to proteins for biochemical assays. Its small size means the biological activity of the protein will most likely be unaffected. This process is called biotinylation
Biotinylation
In biochemistry, biotinylation is the process of covalently attaching biotin to a protein, nucleic acid or other molecule. Biotinylation is rapid, specific and is unlikely to perturb the natural function of the molecule due to the small size of biotin...

. Because both streptavidin
Streptavidin
Streptavidin is a 60000 dalton protein purified from the bacterium Streptomyces avidinii. Streptavidin homo-tetramers have an extraordinarily high affinity for biotin . With a dissociation constant on the order of ≈10-14 mol/L, the binding of biotin to streptavidin is one of the strongest...

 and avidin
Avidin
Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians deposited in the whites of their eggs. In chicken egg white, avidin makes up approximately 0.05% of total protein...

 bind biotin with high affinity (Kd of ~10−15 mol/L) and specificity, biotinylated proteins of interest can be isolated from a sample by exploiting this highly-stable interaction. The sample is incubated with streptavidin/avidin beads, allowing capture of the biotinylated protein of interest. Any other proteins binding to the biotinylated molecule will also stay with the bead and all other unbound proteins can be washed away. However, due to the extremely strong streptavidin-biotin interaction, very harsh conditions are needed to elute the biotinylated protein from the beads (typically 6M Guanidine
Guanidine
Guanidine is a crystalline compound of strong alkalinity formed by the oxidation of guanine. It is used in the manufacture of plastics and explosives. It is found in urine as a normal product of protein metabolism. The molecule was first synthesized in 1861 by the oxidative degradation of an...

 HCl at pH 1.5), which often will denature the protein of interest. To circumvent this problem, beads conjugated to monomeric avidin can be used, which has a decreased biotin-binding affinity of ~10−8 mol/L, allowing the biotinylated protein of interest to be eluted with excess free biotin.

ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...

s often make use of biotinylated primary antibodies against the antigen of interest, followed by a detection step using streptavidin conjugated to a reporter molecule, such as Horseradish peroxidase
Horseradish peroxidase
The enzyme horseradish peroxidase , found in horseradish, is used extensively in biochemistry applications primarily for its ability to amplify a weak signal and increase detectability of a target molecule.-Applications:...

.

See also

  • Avidin
    Avidin
    Avidin is a tetrameric biotin-binding protein produced in the oviducts of birds, reptiles and amphibians deposited in the whites of their eggs. In chicken egg white, avidin makes up approximately 0.05% of total protein...

  • Biotinylation
    Biotinylation
    In biochemistry, biotinylation is the process of covalently attaching biotin to a protein, nucleic acid or other molecule. Biotinylation is rapid, specific and is unlikely to perturb the natural function of the molecule due to the small size of biotin...

  • Multiple carboxylase deficiency
    Multiple carboxylase deficiency
    Multiple carboxylase deficiency is a form of metabolic disorder involving failures of carboxylation enzymes.The deficiency can be in biotinidase or holocarboxylase synthetase.These conditions respond to biotin.Forms include:...

  • NeutrAvidin
    NeutrAvidin
    NeutrAvidin protein is a deglycosylated version of avidin, with a mass of approximately 60,000 daltons. As a result of carbohydrate removal, lectin binding is reduced to undetectable levels, yet biotin binding affinity is retained because the carbohydrate is not necessary for this activity...

  • Photobiotin
    Photobiotin
    Photobiotin derivative of biotin used as a biochemical tool. It is composed of a biotin group, a linker group, and a photoactivatable nitrophenyl azide group....

  • Strep-tag
    Strep-tag
    The Strep-tag® system is a method which allows the purification and detection of proteins by affinity chromatography. The Strep-tag is a synthetic peptide consisting of eight amino acids...

  • Streptavidin
    Streptavidin
    Streptavidin is a 60000 dalton protein purified from the bacterium Streptomyces avidinii. Streptavidin homo-tetramers have an extraordinarily high affinity for biotin . With a dissociation constant on the order of ≈10-14 mol/L, the binding of biotin to streptavidin is one of the strongest...