The Vitamins 177
both free and bound to a serum glycoprotein that
has biotinidase activity, catalyzing the hydrolysis of
biocytin.
Biotin enters tissues by a saturable transport system
and is then incorporated into biotin-dependent
enzymes as the ε-amino-lysine peptide, biocytin.
Unlike other B vitamins, where concentrative uptake
into tissues can be achieved by facilitated diffusion
followed by metabolic trapping, the incorporation of
biotin into enzymes is relatively slow, and cannot be
considered part of the uptake process. On catabolism
of the enzymes, biocytin is hydrolyzed by biotinidase,
permitting reutilization.
Metabolic functions of biotin
Biotin functions to transfer carbon dioxide in a small
number of carboxylation reactions. The reactive
intermediate is 1-N-carboxy-biocytin (Figure 8.17),
formed from bicarbonate in an ATP-dependent reac-
tion. A single enzyme acts on the apoenzymes of
acetyl-CoA carboxylase, pyruvate carboxylase, propi-
onyl-CoA carboxylase, and methylcrotonyl-CoA
carboxylase to form the active holoenzymes from
(inactive) apoenzymes and free biotin.
Biotin also has a role in the control of the cell cycle,
and acts via cell surface receptors to regulate the
expression of key enzymes involved in glucose metab-
olism. In response to mitogenic stimuli there is a con-
siderable increase in the tissue uptake of biotin, much
of which is used to biotinylate histones and other
nuclear proteins.
Biotin defi ciency and requirements
Biotin is widely distributed in foods and defi ciency is
unknown, except among people maintained for many
months on total parenteral nutrition, and a very small
number of people who eat large amounts of uncooked
egg. Avidin, a protein in egg white, binds biotin
extremely tightly and renders it unavailable for
absorption. Avidin is denatured by cooking and then
loses its ability to bind biotin. The amount of avidin
in uncooked egg white is relatively small, and prob-
lems of biotin defi ciency have only occurred in people
eating a dozen or more raw eggs a day, for some
years.
The few early reports of human biotin defi ciency
are all of people who consumed large amounts of
uncooked eggs. They developed a fi ne scaly dermatitis
and hair loss (alopecia). Histology of the skin
showed an absence of sebaceous glands and atrophy
of the hair follicles. Provision of biotin supplements
of 200–1000 μg/day resulted in cure of the skin
lesions and regrowth of hair, despite continuing the
abnormal diet providing large amounts of avidin.
There have been no studies of providing modest
doses of biotin to such patients, and none in
which their high intake of uncooked eggs was
not either replaced by an equivalent intake of cooked
eggs (in which avidin has been denatured by heat, and
the yolks of which are a good source of biotin) or
continued unchanged, so there is no information
from these case reports of the amounts of biotin
required for normal health. More recently, similar
signs of biotin defi ciency have been observed in
patients receiving total parenteral nutrition for pro-
longed periods after major resection of the gut. The
signs resolve following the provision of biotin, but
again there have been no studies of the amounts of
biotin required; intakes have ranged between 60 μg/
day and 200 μg/day.
S
HN NH
O
C
H
N
CH
O
C O
NH
S
NNH
O
C
H
N
CH
O
C O
NH
S
HN NH
O
C
O
O-
Biotin
Biotinyl lysine (biocytin)
Carboxybiocytin
Figure 8.17 Biotin, biotinyl-lysine (biocytin) and the role of biocytin
as a carbon dioxide carrier.
