Synthesis of Thyroid Hormones Flashcards by Marcos J Collazo Acevedo

Describe the step 2 of the biosynthesis of thyroid hormones

Oxidation of iodide to to iodine by thyroid peroxidase (TPO) in the peroxisome

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Triiodothyronine is conjugated, also on the outer ring, with sulfate in a reaction catalyzed by:

Phenol Sulfotransferase

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Mention the function of T3 on the heart

Increase:

Heart Rate
Hypertrophy

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Describe the feedback effect

Entire cycle that delicately balanced to maintain stable levels of thyroid hormones (T3 and T4) in the blood, involving TRH, the pituitary and hypothalamus.

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_____________ condition in which the thyroid gland produces and secretes excessive amounts of thyroid hormones: T3 and/or thyroxin T4.

Hyperthyroidism

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Accounts for 80%􏰁95% of thyroid hormones produced by the thyroid gland

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In children, hypothyroidism leads to delays in growth and intellectual development, which is called _________

Cretinism

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Wich transport mechanism is associated with Iodine?

Sodium Iodide (Na+ I−) symporter (NIS)

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In human beings and monkeys, circulating T4 is bound primarily to:

Thyroxine-binding globulin (TBG)

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The α􏰂-subunit has an identical structure to other hormones (LH,FSH, hCG) but the β􏰃-subunit is specific.

TSH

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What type of reaction occur in the liver, kydeys or elsewhere that is important to metabolism?

Monodeiodination of Thyroxine (deiodination of T4)
- The removal of an iodine molecule from the 5’ position on the outer phenolic ring by 5􏰆-deiodinase results in T3

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Mention the function of T3 on the Bone

Increase:

Growth and maturation
Resorption

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__________is bound to tyrosyl residues in thyroglobulin to form, successively, _____________ and ____________ .

Iodine
Monoiodotyrosine (MIT)
Diiodotyrosine (DIT)

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________ acts on the pituitary gland to trigger more TSH release

TRH

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The number of TRH receptors on the thyrotropes is regulated by:

The concentration of both TRH itself and of the thyroid hormones

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Describe the Step 4 of the biosynthesis of thyroid hormones

Coupling of iodinated tyrosine residues to form either T4 (DIT+DIT) or T3 (MIT+DIT).

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Conjugated thyroid hormones (with sulfate and glucuronic acid) are excreted in the bile, passing into the intestine, where some of the iodine is reabsorbed by ______________

Enterohepatic Circulation

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Increase in intracellular___________ leads to the release of intracellular __________, which in turn results in secretion of ___________.

Inositol triphosphate (IP3 )

Calcium

TSH

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Mention the function of T3 in the liver

Increase:

Cholesterol synthesis
Cholesterol absorption from plasma
Conversion of cholesterol to bile acids
Fat Oxidation/Synthesis Glucogenesis

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Describe the Step 6 of the biosynthesis of thyroid hormones

The thyroid hormones are transported to the plasma membrane and released into the bloodstream

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Mention the autoimmune condition that consist in attack of the immune system to the thyroid gland, specially the follicle cells, and is the most common cause of hypothyroidism

Hashimoto’s Thyroiditis

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______________ are degraded primarily by conjugation in the liver

Thyroid Hormones

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If the ______________ are low, then the ___________ will secrete more TSH and if ______________ levels in the blood are too high, then pituitary gland secretes less ____________.

Thyroid hormones
Pituitary gland
T3 and T4
TSH

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__________ is formed in peripheral tissues by deiodination of T4.

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Glycoprotein heterodimer consisting of an α- and β-subunit

**TSH**

\_\_\_\_\_\_\_\_\_\_ is a tripeptide synthesized in the peptidergic hypothalamic nuclei and transported to the anterior pituitary via the portal circulation.

**TRH** (thyreoliberin)

\_\_\_\_\_\_\_\_\_\_\_\_\_are actively pumped against a gradient into the follicular epithelium and then pass into thyroid follicles, where they are oxidized to\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

Iodide ions (I-) Iodine (I2) molecules

What is the function of the enzyme **Thyroid Peroxidase (TPO)?**

Oxidation of iodide

Tg is ___________ and then secreted into the follicular lumen, where the tyrosine residues are \_\_\_\_\_\_\_\_\_\_\_.

Glycosylated Iodinated

When the thyroid gland needs to be stimulated, the pituitary gland secretes \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_

**Thyroid stimulating hormone (TSH)**

Coupled receptors on the pituitary thyrotrope cell membrane that are linked to phospholipase C

G protein

\_\_\_\_\_\_\_\_ is the major form of thyroid hormone secreted from the gland

Why T3 is found in higher concentrations in some intracellular tissues?

Because T3 binds to THRs with **higher affinity** than T4

Is secreted by the hypothalamus to act in compound with the pituitary gland:

Thyrotropin-releasing hormone (TRH)

Where is located the transporter protein for iodine?

Present in the **basolateral** membrane of: * Thyroid follicular cells (thyrocytes) such as the salivary gland, * Gastric mucosa * Lactating mammary gland

If a molecule of iodine is removed from the **5 position** of the **inner phenolic** ring of T4 by another enzyme, **5- deiodinase,** the final product woul be:

**Reverse T3 (3,3􏰆,5􏰆- triiodothyronine)** Biologically Inactive

The following are less common causes of wich disease * Treatment with radioactive iodine * Injury to the hypothalamus or the anterior pituitary gland * Certain medications * Lack of a functioning thyroid at birth or previous thyroid surgery

**Hypothyroidism**

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_is primarily controlled by **negative feedback** regulation of the **hypothalamic-pituitary-thyroid (HPT)** axis via **thyroid hormone receptor (THR) signaling**.

**Thyroid Hormone Production**

Describe the **step 1** of the biosynthesis of thyroid hormones

Iodide is concentrated in follicular epithelial cells after entry via a sodium iodide symporter

Describe the **Step 5** of the biosynthesis of thyroid hormones

Thyroglobulin is exocytosed and hydrolyzed in lysosomes to release free T4 and free T3

Describe the **Step 3** of the biosynthesis of thyroid hormones

At the plasma membrane adjacent to the follicular lumen conversion of tyrosyl (Y) residues on the surface of the thyroid glycoprotein thyroglobulin to either monoiodotyrosine (MIT) or diiodotyrosine (DIT).

Who helps the body use energy, stay warm and keep the brain, heart, muscles, and other organs working as they should?

Thyroid Hormones

Release **TRH**

The paraventricular nucleus of the hypothalamus

Is an aromatic 􏰂α-amino acid that is found in most proteins (such as insulin)

Tyrosine

Is formed by the 5􏰆 deiodination of T4 by deiodinases

80% of T3

Thyroxine is conjugated on the outer phenolic ring with glucuronic acid in a reaction catalyzed by:

**Thyroxine UDP Glucuronosyltransferase** Conjugated T4 is escreted in bile

Mention the function of T3 in the **adipocytes**

**Increase** fatty acid mobilization

Butterfly-shaped endocrine gland that is normally located in the lower front of the neck.

Thyroid Gland

The most common cause of hypothyroidism worldwide is:

Too **little iodine** in the diet

Is a common endocrine disorder in which the thyroid gland does not produce enough thyroid hormone **Symptoms:** * **Tiredness** * **Poor ability to tolerate cold** * **Weight gain.**

Hypothyroidism

Consists of spherical follicles comprising a single layer of cuboidal epithelial cells surrounding the follicle lumen

Thyroid

Wich is the main composition of the homogenous colloid of the thyroid?

Thyroglobulin (Tg)

**TSH** synthesis and secretion is stimulated by: the binding of ______ to \_\_\_\_\_\_\_\_\_

**TRH** to **G protein**

Who controls the level of thyroid stimulation based on the levels of thyroid hormones (T3 and T4) in the blood?

**Pituitary Gland**

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ is a high molecular weight glycoprotein synthesized in ribosomes of the endoplasmic reticulum in follicular cells.

Thyroglobulin

\_\_\_\_\_\_\_\_\_ stimulates thyrotrophs of the anterior pituitary to secrete \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_.

thyroid- releasing hormone **(TRH)**, Thyroid-stimulating hormone **(TSH)**.

Is complex (16 exons, 14 introns) and its expression in the thyroid is upregulated by TSH

The sodium iodide (Na+ I− ) symporter NIS gene

**Iodine** combines with **tyrosine** attached to **Tg** to produce:

Monoiodotyrosine (MIT) and Diiodotyrosine (DIT)

Is released by the anterior pituitary and stimulates the thyroid follicular cells to release thyroxine.

**TSH**

Most common cause of Hyperthiroidism, autoimmune disease. It most commonly affects the thyroid, frequently causing it to enlarge to twice its size or more (goiter), become overactive, with related hyperthyroid symptoms such as increased heartbeat, muscle weakness, exophtalmos disturbed sleep, and irritability.

Grave's Disease

The follicular cells of the thyroid glands are the secretory units for which of the bioactive hormones?

**Thyroxine (DIT + DIT)**, also known as T4 **Triiodothyronine (MIT + DIT)**, also known as T3

MIT and DIT combine to form:

The two biologically active iodothyronines secreted by the thyroid gland * **Thyroxine T4** * **Triiodothyronine T3** 􏰁

\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_ can selectively **inhibit the NIS** and **active transport of iodide**, thereby effectively blocking the ability of the gland to synthesize thyroid hormones.

**Perchlorate** and **Thiocyanate**

\_\_\_\_\_\_\_\_\_\_\_ is exocytosed and hydrolyzed in lysosomes to release free T4 and free T3.

Thyroglobulin (Tg)

Is the major active intracellular form of thyroid hormone

\_\_\_\_\_\_\_\_\_\_\_is a precursor of such important chemical as epinephrine, norepinephrine, dopamine, thyroid hormones, and melanin.

Tyrosine

Mention the actions of **TSH**

* Uptake of iodide into thyroid follicular epithelium * Thyroglobulin (Tg) synthesis and secretion * Iodination of thyroglobulin (Tg) tyrosine residues * T4 and T3 secretion into the circulation.

Is a dimeric molecule containing 115􏰁-123 tyrosine residues that is produced in the thyroid cells and secreted into colloid

Thyroglobulin (Tg)

\_\_\_\_\_\_\_\_\_\_\_\_is used to ablate residual tumor tissues as well as recurrent and metastatic thyroid cancer

Radioiodine

Is part of the rhodopsin-like G protein􏰁coupled receptor family and is present on the basolateral membrane of follicular cells of the thyroid

The **receptor** for **TSH**

Is regulated by the stimulatory action of TRH and the inhibition of T4 and T3.

TSH Production

Binds to an extracellular domain with high affinity and acts via a G protein

**TSH**

Accelerate the metabolism significantly, causing sudden weight loss, a rapid or irregular heartbeat, sweating, and nervousness or irritability

Hyperthiroidism

Synthesis of Thyroid Hormones Flashcards

(73 cards)