*B7

*Discovered due to "egg white injury"

-Eating raw eggs = hair loss and dermatitis

-A substance in liver (biotin) can cure it

BIOTIN - Sources

*Egg yolks, liver, soybeans, yeast

*(not in veggies, fruit, meat)

*Commonly found in foods bound to protein or as biocytin

*Also produced by bacteria in colon

*AKA biotinyllysine

*Biotin + Lysine

*Biotin is found either bound covalently to protein or as biocytin

*Biotin bound in amide linkage to amino groups of lysine or lysine residues (carboxylases)

Biotin binders

*Avidin: a glycoprotein in raw egg whites, irreversibly binds to biotin, and prevent its absorption (& decrease bioavailability) - heat labile

*Streptavidin: bacterial analog of avidin

*Tamavidin: avidin-like protein in tamogitake mushroom

*Proteolysis: Biotin-bound to protein ->Biocytin

*Biotinidase: Biocytin -->biotin and lysine

*Biotinidase: found on BBM and pancreatic and intestinal juices

*In most body cells

*Biotinidase deficiency: genetic disorder of metabolism: seizures, ataxia, skin rash, hair loss

BIOTIN – Absorption & Transport

*Free biotin is absorbed mostly in jejunum and ileum by SMVT (like PA and lipoic acid) found in SI (across the Brush Border Membrane)

-Passive Diffusion at high doses

-Carrier mediated and Na⁺-dep at low doses

*High absorption rate for ingested biotin (~100%)

-Alcohol can inhibit biotin

BIOTIN – Absorption & Transport

*Carrier-mediated transport across basal lateral membrane of enterocyte

*In blood, ~80% of biotin found is free form and little amount of protein bound form

*Some undigested biocytin may be absorbed intact by peptide carriers and hydrolyzed by biotinidase present in blood or in other tissues

BIOTIN – Absorption & Transport

*Uptake into the liver and other tissues by SMVTs and other carriers

*Stored in small quantities in muscle, liver, and brain

*PROTEASES: Biotin-dep enzymes (biotin holocarboxylases) ->biotcytin

*BIOTINIDASE: Biocytin-->Biotin-->Reused or degraded

*Excretion

-Biotin, biocytin, and other metabolites are excreted in urine

-Any absorbed biocytin not metabolized by biotinidase is excreted in the urine

-Unabsorbed biotin and biotin produced by intestinal bacteria that is not absorbed is excreted in the feces 

-

*A coenzyme for carboxylases

*Noncoenzyme in gene expression and cell signaling

*The biotin is attached in an amide bond to lysine residue of carboxylases

*The flexible chain connecting biotin and the apoenzyme allows the biotin to move from one active site of the carboxylase to another

*One active site on apoenzyme generates the carboxybiotin (CO₂-biotin) enzyme, and the other transfers the activated CO₂ to a reactive carbon on the substrate

Summary of Carboxylases

*Cell proliferation, gene silencing, DNA repair

-Histone biotinylation: biotin is attached to histones mediated by holocarboxylase synthetase

-Biotinylation of histones appears to:

-Increase in response to cell proliferation

-Increase in the cellular response to DNA damage

*Gene Expression and Cell Signaling

* >2000 genes depend on biotin for expression

*>25% of these genes play a roll in cell signaling

*Enhances the availabilit for translation of mRNAs for glukokinase and some other enzymes

*AI for Men/Women: 30micro g/d

*Plasma

*Urine

*Deficiencies rare, but there can be other causes for depressed function of biotin

*Biotinidase deficiency

*Biocytin builds up, not enough biotin will be made

*Causes carboxylase deficiencies

*Decreases the release of biotin from dietary protein = decrease intestinal absorption

*Recycling of biotin bound to protein is impaired, and urinary loss of biotin is increased bc kidneys excrete free biotin more rapidly

*Hair loss, rash, neurologic symptoms, lethargy, hallucination, numbness

*Requires supplementation

*Holocarboxylase synthetase deficiency:

-Results in decreased formation of all carboxylases at normal blood levels of biotin

-Fatal if not treated, symptoms occur soon after birth: severe ketoacidosis, seizures, coma

-Milder cases also require treatment: rash, alopecia

*Alcohol, raw eggs, mushrooms, avidin

*Depression, hallucinations, muscle pain, localized paresthesia, anorexia, nausea, alopecia, scaly dermatitis

*Localized paresthesia: abnormal feeling of burning and prickling

*UL not determinable

*No toxicity

*Use of biotin as hair and skin conditioning agent in cosmetics = safe