This document summarizes the absorption, transport, and metabolism of biotin in the human body. It discusses how biotin is released from food proteins and absorbed through both facilitated transport and passive diffusion in the small intestine. It then describes how biotin circulates in the bloodstream, is taken up by cells through sodium-dependent and monocarboxylate transporters, and is stored in tissues like the liver. Finally, it outlines how biotin is attached to carboxylase enzymes, recycled through cleavage by the enzyme biotinidase, catabolized, and excreted in the urine and feces.

1. Absorption, transport and
metabolism of biotin
Domina Petric, MD

2. Absorption of biotin
I.

3. Liberation from bound forms
• In the digestion of food proteins, protein-
bound biotin is released by the hydrolytic
action of the intestinal proteases to yield
the ε-N1-biotinyllysine adduct, biocytin,
from which free biotin is liberated by the
action of an intestinal biotin amide
aminohydrolase, biotinidase.

5. Facilitated transport
At low concentrations, biotin is
absorbed by a saturable, facilitated
mechanism dependent on Na+.
This process has been found to be
inhibited by certain anticonvulsant
drugs and chronic ethanol exposure.
The inhibitory effect of ethanol has
been demonstrated with solutions as
dilute as 1% (v/v).

6. Facilitated transport
Similar inhibition has been
demonstrated for ethanol against
biotin transport in human
placental basolateral membrane
vesicles, which also occurs by an
Na+-dependent, carrier-mediated
process.

7. Passive diffusion
At high lumenal
concentrations, free biotin
is also absorbed by
nonsaturable, simple
diffusion.

8. Transport of biotin
II.

9. Unbound biotin
• Less than half of the total biotin
present in plasma appears to be free
biotin, the balance being composed of
bisnorbiotin, biotin sulfoxide and
other metabolites.
• Only 12% of the total biotin in human
plasma is covalently bound.

10. Cellular uptake

11. Sodium-dependent vitamin transporter
(SMVT)
• A Na+-dependent, carrier-mediated process
that is not specific for the vitamin, but that
functions in the cellular uptake of biotin,
pantothenic acid and lipoic acid with similar
affinities.
• Biotin uptake by intestinal cells is inhibited by
the activation of protein kinase C,
apparently through phosphorylation of SMVT.

12. Monocarboxylate transporter
• That this member of the monocarboxylate
tansporter family can facilitate the cellular
uptake of biotin into peripheral blood
mononuclear cells explained the facts that
biotin is taken up by those cells by process
with a Km three orders of magnitude less
than that for SMVT-mediated transport,
and is not competitively inhibited by
either pantothenic or lipoic acids.

13. Tissue distribution
• Appreciable storage of the vitamin appears to
occur in the liver: 800-3000 ng/g.
• Most of this appears to be in mitochondrial
acetyl CoA carboxylase.
• Hepatic stores appear to be poorly mobilized
during biotin deprivation and do not show the
reductions measurable in plasma under such
conditions.

14. Metabolism of biotin
III.

15. Linkage to apoenzymes
• Free biotin is attached to its apoenzymes via
the formation of an amide linkage to the
ε-amino group of a specific lysine residue.
• In each of the four biotin dependent enzymes,
this binding occurs in a region containing the
same amino acid sequence: -Ala-Met-biotinyl-
Lys-Met-.
• It is catalyzed by biotin holoenzyme
synthetase.

16. Recycling the vitamin
The normal turnover of the biotin-containing
holocarboxylases involves their degradation to yield biocytin.
The biotinyl lysine bond is not hydrolyzed by cellular
proteases-it is cleaved by biotinidase to yield free biotin.
Biotinidase is the major biotin-
binding protein in plasma.
It is also present in breast milk, in which its
activity is particularly high in colostrum.

17. Recycling the vitamin
• The proteolytic liberation of biotin from its bound
forms is essential for the reutilization of the
vitamin, which is accomplished by its
reincorporation into another holoenzyme.
• Congenital deficiencies of biotinidase are
characterized by deficiencies of the multiple
biotin-dependent carboxylases.
• In some cases, they can be corrected with
pharmacologic doses of the vitamin.

18. Catabolism
A small fraction of biotin is oxidized to
biotin D- and L-sulfoxides, but the ureido
ring system is not otherwise degraded.
The side chain of a larger portion is metabolized
via mitochondrial β-oxidation to yield bisnorbiotin
and its degradation products.
Biotin catabolism appears to be greater
in smokers than in nonsmokers.

19. Excretion
• Biotin is rapidly excreted in the urine.
• Half of urinary biotin occurs as free biotin, other
half is composed of bisnorbiotin, bisnorbiotin
methyl ketone, biotin sulfone, tetranorbiotin-L-
sulfoxide and various side-chain products.
• Unabsorbed biotin appears in the feces.
• Only a small amount (<2% of an intravenous
dose) of biotin is excreted in the bile.

20. Literature
• Combs GF. The Vitamins. Fundamental Aspects in
Nutrition and Health. Elsevier Inc. 2008.