Biotin Flashcards
What vitamin is biotin?
B7
Biotin properties
- sensitive to heat
- solvent extraction, heat curing & food canning
Biotin structure and active sites
the ketone makes it reactive and 6he 2 nitrogen’s are the active parts involved in reactions
What are the different forms of biotin?
8 stereoisomers possible
* only D-biotin found in nature & biologically active
* Biocytin = bound to lysine
* Carboxybiotin = active form
What is the active form of biotin?
Carboxybiotin
How does biotin function
- Functions as the prosthetic group in 4 carboxylases, serving as a CO2 carrier & donor
- Also some non-coenzyme roles
What 4 carboxylases does biotin serve as a prosthetic group?
- pyruvate carboxylase (PC) in mito
- propionyl CoA carboxylase (PCC) in mito
- acetyl CoA carboxylase (ACC) in cytosol
- 3-methylcrotonyl CoA carboxylase (MCC) in mito
How does biotin activate the enzymes
- biotin activation: biotin + ATP→ biotin-AMP (biotinyladenylate) + PPi
- biotin-AMP is added to an apocarboxylase (containging lysine) through covalent bond via holocarboxylase synthetase to become the holocarboxylase (biotin-enzyme) and releasing the AMP
How does the biotin on the holocarboxylase accept CO2 to be transferred?
Addition of CO2 to biotin requires ATP, bicarbonate and Mg2+, therefore the reaction requires energy
1. hydrolyze ATP to dehydrate HCO3 to a phosphorylated CO2
2. The biotinyl-enzyme can then be carboxylated with the release of the phosphate group
How does the biotin donate the CO2?
carboxylates the substrate
* requires Mg2+
* requires energy: ATP→ADP
Describe the PC enzyme
pyruvate carboxylase which is neccessary for gluconeogenesis
* converts pyruvate (from AA) → oxaloacetate (which then becomes PEP or goes to TCA)
What happens with PC deficiency?
would get build up of pyruvate which leads to lactic acidosis and inrease risk for ammonia
Describe the PCC enzyme
propionyl CoA Carboxylase is needed for odd chain FA metabolism (also Val, Ile and propionate)
* converts propionyl CoA → methylmalonyl CoA
* methylmalonyl CoA is then converted to succinyl CoA via a B12-dependant isomerase which can enter TCA
What happens with PCC deficiency?
- propionic acidosis
- ketoacidosis
Describe the ACC enzyme
acetyl CoA carboxylase needed for fatty acid synthesis
* converts acetyl CoA → malonyl CoA which eventually goes to fatty acids
* in cytosol = rate- limiting step for FA synthesis
* in mitochondria = regulation of FA uptake for oxidation
Deficiency in ACC
No inherited genetic deficiency of ACC documented because it is so important it would be lethal if it stopped working at any point
Dsecribe the MCC enzyme
3-methyl-crotonyl-CoA carboxylase is needed for Leu catabolism
* leu becomes 3-methyl-crotonyl-CoA and MCC then carboxylates it to 3-methyl-glutaconyl CoA
Deficiency in MCC
severe acidosis
Biotin non-coenzyme functions
- pharmocological roles
- role in epigenetics
pharmocological roles of biotin
Pharmacological levels of biotin acts to induce glucokinase
* promotes transcription & translation of gene
* liver = permits rapid uptake & metabolism of glucose
* pancreas = acts as the signal for insulin release
Biotin role in epigenetics
- Histone biotinylation via lys = down regulates certain genes
- regulates transcription & cellular responses to DNA damage
Biotin Metabolism
- intesinal lumen: protein complex broken down by GI proteases yielding biocytin which is broken down biotinidase to yield biotion
- into enterocyte: Biotin enters enterocyte cell through a multivitamin transporter, some biocytin enters enterocyte through diffusion(?)
- absorption: Secreted out as free biotin, some bound to proteins, and biocytin (which gets converted to free biotin by biotinidase in circulation)
- Liver: Liver extracts majority & is major site of biotin utilization & metabolism
- Some biotin is secreted from liver and goes to other tissue
How is biotin absorption regulated?
absorption ↑ during deficiency and ↓ during excess by changing the number of functional carriers
How can biotin be reused?
When protein is broken down during turnover it yields biocytin in the cell and through biotinidase it can be reused for intracellular biotin for carboxylase biotinylation or histone biotinylation
Biotin reabsorption and excretion
- renal reabsorption is essential for biotin homeostasis & conservation and uptake is carrier-mediated & Na-dependent
- most excretion is as biotin, some other metabolites/degradation products
Biotin food sources
Biotin is in almost all foods in relatively low content and is available as free biotin & biotinyl-proteins/ biocytion
* protein-bound = animal products, nuts, cereals
* free = vegetables, green plants, fruit, milk
* not commonly used in fortified foods
Other sources of biotin
synthesized by microflora in large intestine
* not sure of availability
* urinary & fecal content of biotin > dietary intake
what can effect biotin recycling
biotinidase impairment
* can lead to symptoms of deficiency
Biotin DRIs
no RDA set so it is AIs (µg)
* M/F = 30 µg/d
* increases with lactation
* daily dietary intake is estimated at 50-300 μg/d
* TPN patients = 60 μg/day recommended
* no UL set
What can be used to measure biotin status
- blood/serum (insensitive since renal reabsorption will increase with less intake and serum can be normal even with clinical signs of deficiency)
- urine for biotin and metabolites
- 3-hydroxyisovalerate = measure of MCC activity
- other
- lymphocyte PCC activity
- lymphocyte FA composition
Inborn errors for biotin
- Holocarboxylase synthetase deficiency
- Biotinidase deficiency
Holocarboxylase synthetase deficiency
multiple carboxylase deficiency which results in ↓ activity of all 4 biotin-containing carboxylases
* S/S = dermatitis, alopecia, severe ketoacidosis, seizures
biotinidase deficiency
unable to release free biotin from foods & to recover it from enzymes = functional deficiency
* S/S = seizures, ataxia, developmental delay, skin rash & hair loss
Biotin deficiency
Rare
* Activities of carboxylases ↓
How do raw eggs effect biotin availability
Raw egg whites = contain avidin which binds biotin and make it unavailable but biotin is heat labile therefore cooking eggs denatures it & destroys biotin-binding property of avidin
Why is at risk of biotin deficiency?
- low levels in infants, alcoholics, & pregnancy
- treatment with antibiotics can reduce microbiomes production
- patients on TPN if not put in
