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transcobalamin

Transcobalamin refers to a family of vitamin B12–binding proteins that mediate the transport of cobalamin (vitamin B12) in the bloodstream and to tissues. In humans, the main members are transcobalamin I (TCN1, also known as haptocorrin), transcobalamin II (TCN2, transcobalamin), and transcobalamin III (TCN3). TCN1 is produced in various tissues and secreted into plasma and other fluids; it binds corrinoids including vitamin B12 but does not efficiently transfer them to cells, instead helping to protect cobalamin in the circulation and in secretions. TCN2 is the principal transport protein for cobalamin in blood and forms holo-transcobalamin (holo-TC) when bound to a molecule of cobalamin. The holo-TC–cobalamin complex is recognized by the cellular receptor CD320 (transcobalamin receptor), allowing uptake of cobalamin into cells where it is converted to the active cofactors methylcobalamin and adenosylcobalamin. The holo-transcobalamin fraction represents the bioavailable portion of vitamin B12 in the circulation; total serum B12 includes holo-TC as well as B12 bound to TCN1 and other proteins.

TCN3’s role is less clearly defined; some studies suggest tissue-associated or regulatory functions with limited involvement

in
plasma
transport.
Clinically,
measurement
of
holo-transcobalamin
is
used
as
an
early
indicator
of
B12
status,
sometimes
more
sensitive
than
total
B12.
Rare
congenital
deficiencies
of
transcobalamins,
particularly
TCN2,
cause
impaired
cellular
delivery
of
B12,
leading
to
megaloblastic
anemia
and
neurological
symptoms
despite
variable
serum
B12
levels;
treatment
typically
involves
high-dose
parenteral
vitamin
B12.