Phar_401_ Thyroid_Swanson

Front 1

what are the 5 steps of biosynthesis and metabolism of the thyroid hormones

Back 1

•Uptake of I-
•Oxidation of I- and iodination of Tyr residues in thyroglobulin (Tg)
•Coupling of DIT
•Proteolysis of Tg, secretion and transport of T4 to peripheral tissues
•Conversion of T4 to T3 in peripheral tissues

Front 2

what is the transporter on the thyroid gland to let Iodine concentrate into the follicular cell? what other transporter is it coupled with? What anions can cock-block the transport?

Back 2

* Na/I Symporter. It is regualted by TSH and the inward flow of I is coupled with Na+. This pump is coupled with Na+/K pump which supplies energy to NIS at cost of 1ATP.
* –Perchlorate ClO4-
* –Pertechnate TcO4-
* –Thiocyanate SCN-

2K in, 3NA out

Front 3

Explain the organification rxn of iodotyrosins

Back 3

Iodine is oxidized by thyoid peroxidase (TPO) to get an iodide and incorporating the iodide in two iodination reactions of Tyr -> MIT-> DIT this takes place in the thyroid follicle lumen

Front 4

explain coupling reaction of iodotyrosins...targeted?

Back 4

* this step is targeted by some antithyroid drugs and high dose iodine tx.
* TPO comes around again and takes (usually) 2 residues of DIT and get conjugated together to make (usally) T4

Front 5

explain the proteolysis of Tg

Back 5

thyroid follicluar cell gets timulated by TSH, Tg gets in a vesicle from lumen and then fuses with lysosome. Tg gets digested to primary AA and releases T4/T3. the left over MIT,DIT get recycled

Front 6

Explain the Conversion of T4 to T3 in peripheral tissues

Back 6

* T4 gets converted into the active T3 by iodine deiodinases.
* D1 is in the kidneys, thyroid, and liver and is inhibited by PTU
* D2 is in the target tissues that respond to thyroid hormone targeted by T3 and
* D3 5’ is present in all tissues and creates an inactive t3

Front 7

what are the 2 ions to block thyroid hormone production at the NIS?

Back 7

perchlorate ClO4
pertechnate TcO4
bonus:
thiocyanate SCN

Front 8

how does propylthiouracil used to inhibit thyroid production?

Back 8

propylthiouracil (PTU) is used which inhibits type 1 5’ deiondinases and TPO
requires a C2 thioketo/thienol and propyl at C6...shortening or lengthening propyl decreases activity
With TPO, it takes an activated Iodine off so TPO can’t put it on a tyr

Front 9

how do MMI work in inhibiting thyroid production?

Back 9

methimazole works in the same way as PTU but it is 10xmore potent than PTU.
doesn’t inhibit type 1 deiondinases because of its methyl in N1 position

Front 10

• how and which radiation is used to treat hyperthyroidism

Back 10

use radioactive Iodine131 which degrades to xenon131 and emits beta particle and destroys cells in the thyroid

Front 11

explain direct destruction by beta particle

Back 11

breaks C=C in DNA and other key molecules. splits backbone of DNA causing mutations causing chromosal abberations and blocking DNA synthesis

Front 12

explain indirect destruction by beta particle

Back 12

forms OH radicals through intereaction of H2O. the hydroxyl radical causes oxidative damage to DNA and other cellular targets...more damage

Front 13

ionization of what part of T4 is important for binding to plasma proteins?

Back 13

ionization of the 4' OH is important

Front 14

whaqt are the thyroid binding proteins?

Back 14

thyroxin-binding globulin
transthyretin
albumin