Biotin
• Structure consists of two rings and a valeric
acid side chain
• Sources
– liver, soybeans, egg yolk, cereals, legumes, nuts
– often found bound to protein
• biocytin o or biotinyllysine
– avidin binds biotin and inhibits absorption
• glycoprotein found in egg whites
• heat labile so cooking denatures
Biotin
• Digestion and Absorption
– Protein bound biotin requires digestion by
proteolytic enzymes
• yields free biotin or biocytin
• Biotinidase hydrolyzes biocytin to free biotin
and lysine
• Undigested biocytin may be absorbed and
digested in plasma by biotinidase
• Unmetabolized biocytin is excreted in urine
Biotin
• Biotinidase
– Deficiency due to inborn error has been
documented in infants and children
– Clinical features include seizures, ataxia, skin
rash, alopecia, acidosis
• Bioavailability
– varies from 100% in corn to 0% in wheat
• Absorption
– most takes place in proximal SI by active
transport.
Biotin
• Transport
– Free or protein bound
• Uptake
– related to needs of cells
• Storage
– most found in muscle, liver and brain
• Bacterial Synthesis of biotin
– may be absorbed into body or excreted in
feces
Biotin Functions
• Biotin must be activated to biotinyl 5’adenylate
– biotin reacts with a ATP (Mg required)
– carboxylase joins the biotinyl moiety to form
holoenzyme carboxylase with release of AMP
• Biotin dependent enzymes
–
–
–
–
acetyl CoA carboxylase
pyruvate carboxylase
propionyl CoA carboxylase
Beta-methylcrotonyl CoA carboxylase
Biotin
• Carboxylases
– biotin is attached by an amide linkage
– carboxy terminus of biotin is linked to
epsilon amino group of a specified lysine
residue of apoenzyme
– chain connecting biotin and apoenzyme is
long and flexible
• allows biotin to move from one active site to
another
• see figure 9.23 and 9.24a
Pyruvate Carboxylase
• adds a carboxyl group to pyruvate
forming oxaloacetate
– requires presence of acetyl CoA as well as
ATP and Mg
• acetyl CoA serves as allosteric activator
– Fate of OAA
• if surplus of ATP, gluconeogenic pathway
• if deficiency of ATP, TCA cycle
– see Figure 9.24b
Acetyl CoA Carboxylase
• Initiation of fatty acid synthesis
• Transfers a carboxyl group to acetyl
CoA forming malonyl CoA
• Activated by citrate and isocitrate
• Inhibited by palmitoyl CoA
Propionyl CoA Carboxylase
• Important for catabolism of isoleucine,
threonine and methionine and odd chain fatty
acids
• Catalyzes the conversion of propionyl CoA to
methylmalonyl CoA
• Methylmalonyl CoA converted to succinyl
CoA via vitamin B12 dependent enzyme
Beta-methylcrotonyl CoA
Carboxylase
• During leucine catabolism
– beta-methylcrotonyl CoA is formed
– carboxyl group added to betamethylcrotonyl CoA to form betamethylglutaconyl CoA
• defect in BMCC results in accumulation of
methyl crotonylglycine and hydroxyisovaleric
acid
– further catabolized to acetoacetate and
acetyl CoA
Genetic Defects of Carboxylases
CH3-crotonyl Leucine
glycine
3-methylcrotonyl
CoA
OHisovaleric
BMCC
acid
3-methylglutaconyl
CoA
Malonyl
CoA
Acetyl CoA
ACC
Fatty Acids
Glucose
BCAA
Threonine
Methionine
Odd Chain FA
Propionyl CoA
Pyruvate
PC
Oxaloacetate
Citrate
Succinyl
CoA
PCC
Methylmalonyl
CoA
Metabolism and Excretion
• Catabolism of holocarboxylases by
proteases yields biocytin
• Biocytin degraded by biotinidase to yield
free biotin
• Some of free biotin is reused; some is
further degraded to bisnorbiotin
• See free biotin, bisnorbiotin and biocytin
in urine primarily
Biotin
• AI
– 30 g/d (adult males and females)
• Deficiency
– depression, hallucinations, muscle pain,
nausea, scaly dermatitis
• excessive ingestion of raw egg white
• GI disorders
– IBD
– achlorydia
• Excessive alcohol ingestion
• Certain medications
Biotin
• Toxicity
– none observed
• Assessment
– Evaluation of biotin in
• blood, plasma or serum
• urine