Biology Reference
In-Depth Information
I
Tyrosine
H
Dimerization
HO
Iodination
I
I
H
Thyroglobulin
HO
Residues
condensation
I
I
*
Cleavage
HO
I
I
I
I
HO
*
HO
O
I
I
I
T4
I
O
T3
I
O
I
HO
3
¢
I
3
HO
D1, D2
OH
OH
NH
2
5
¢
O
5
NH
2
I
O
I
ORD
I
D1, D3
IRD
T2
(3,5)
O
D1, D3
IRD
HO
I
OH
NH
2
O
T2
(3,3
¢
)
I
I
O
rT3
I
I
O
HO
D1, D2
I
HO
OH
NH
2
OH
O
ORD
NH
2
T2
(3
¢
,5
¢
)
I
O
I
O
HO
OH
NH
2
O
I
Figure 14.1 Synthesis of thyroid hormones. ORD: outer-ring deiodinase; IRD: inner-ring
deiodinase; T4: thyroxine, native form, the numbers correspond to the iodine atoms; T3:
3,3
0
,5-triiodothyronine, most active form; rT3: 3,3
0
,5
0
-triiodothyronine, inactive form; T2:
3,3
0
-diiodothyronine, inactive form; T2: 3
0
,5
0
-diiodothyronine, inactive form; T2: 3,5-
diiodothyronine, active in certain condition. Adapted from
Bianco and Kim (2006)
and
Gavaret et al. (1981)
.
triiodothyronine) or the active T3 into the inactive 3,3
0
-T2. This
inactivating deiodination is catalyzed by D1 and D3 (
Kuiper, Kester,
Peeters, & Visser, 2005
). Thus, deiodinases can have opposite roles, D2 be-
ing associated with active hormone production, whereas D3 is considered as
a degrading enzyme. The balance between the two enzymes is important in
the homeostatic regulation of T3 levels in peripheral organs. The function of
D1, however, is not yet fully understood. It is the main deiodinase expressed
in the liver but the part of its contribution to the circulating T3 is not clearly
established (for review, see
Darras & Van Herck, 2012
). This enzyme might
be used as a mechanism to recycle the iodine atom (for review, see
Orozco,
Valverde, Olvera, & Garc´a, 2012
).
