Table 2 General characteristics of the iodothyronine deiodinases [16]

Reaction kinetics

Ping-pong

Sequential

Sequential

Reaction catalyzed (Deiodination)

5 or 5' (ORD+IRD)

5' (ORD)

5 (IRD)

Main form

T4-T3, rT3- T2

- T4- rT3, T3- T2

- T4- rT3- T2

Substrate preference

5: T4S>T3S>>T3, T4

T4>rT3

T3>T4

5': rT3, rT3S>T2S>>T4

Sulfation of substrates

Stimulation

Inhibition

Inhibition

Substrate limiting KM

0.5 mM

1–2 nM

5–20 mM

In vitro cofactor limiting KM

1–10 Mm DTT

>10 mM DTT

=70 mM DTT

Molecular mass (kDa)

29

30

32

Selenocysteine

present

present

present

Homodimer

Yes

Yes

Yes

Location

- Liver, kidney, thyroid and pituitary.

- Pituitary, brain, BAT, thyroid^a, heart^a and skeletal muscle^a.

- Brain, skin, uterus, placenta, fetus and in other sites of the maternal- fetal interface, such as the umbilical arteries and veins.

Subcellular location

- Liver: endoplasmic reticulum. - kidney: basolateral plasma membrane

- Microsomal membranes

- Microsomal membranes

Functions

- Production serum T3 and the clearance of serum rT3.

- Catalyzes the outer ring deiodination of T4 to T3 and is thus important for the local production of T3.

- Catalyzes the inner ring deiodination of T4 to rT3 and of T3 to 3,3'-T2.

Activity in hypothyroidism

- Decrease in liver and kidney.

- Increase in all tissues.

- Decrease in brain.

- Increase in thyroid.

Low-T3 syndrome

- Decrease

- No change

- No change

Active site residues

- Selenocysteine histidine and phenylalanine.

- (Seleno-)cysteine?

- Selenocysteine

Human gene structure and location

- 1p32-p33, 17.5 kb and 4 exons.

- 14q24.3, 2 exons and 7.4-kb intron.

- 14q32

Promoter elements

- TRE, RXR, no CAAT or TATA box.

--

--

Propylthiouracil inhibitor

+

+/-

Aurothioglucose inhibitor

++

++

Iopanoic acid inhibitor

+++

++++

+++

Thiouracils

++++

-/+

-

Iodoacetate

+

?

Flavonoids

+

+++

+++