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MD1 Endocrine > Iodine Metabolism and Thyroid Hormones > Flashcards

Iodine Metabolism and Thyroid Hormones Flashcards

1
Q

What are the main steps in thyroid hormone synthesis?

A
  1. Synthesis and secretion of thyroglobulin (TG)
  2. Uptake of iodide by Na/I symporter and excretion by I transporter
  3. Iodination and coupling iodotyrosine of TG
  4. Uptake of iodinated TG and its proteolysis to make T4 and T3
  5. Export of T4 and T3 via monocarboxylic acid transporter 8 (MCT8)
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2
Q

How many tyrosine residues of thyroglobulin out of 134 are iodinated?

A

6-34

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3
Q

What makes thryoglobulin?

A

Thyroid follicular cell

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4
Q

What happens to thyroglobulin after it is synthesised?

A

Secreted into lumen of thyroid follicle

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5
Q

How is iodide taken up by the thyroid follicular cell?

A

By Na/I symporter

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6
Q

How is iodide exported out of the thyroid follicular cell and into the lumen of the thyroid follicle?

A

Unknown iodide transporter

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7
Q

What is the clinical application of radioactive iodine (I-131)?

A

Therapy for treatment of Graves disease

Radioactive damage of follicular cells

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8
Q

Which enzyme iodinises tyrosine?

A

Thyroid peroxidase (TPO)

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9
Q

Which enzyme couples iodotyrosine of TG?

A

TPO

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10
Q

Into where is iodinated TG taken?

A

Thyroid follicular cells

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11
Q

What happens to iodinated TG once it is taken into thyroid follicular cells?

A

Proteolysis to form T4 (and T3)

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12
Q

How are thyroid hormones exported out of thyroid follicular cells?

A

Via MCT8

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13
Q

How are thyroid hormones taken up by target tissues?

A

Via MCT8

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14
Q

What does over-stimulation of the TSH receptor by an autoantibody against it cause?

A

Overproduction of T3 and T4

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15
Q

Which step in the synthesis of thyroid hormones can antithyroid drugs inhibit?

A

Iodination and coupling of iodine and TG by blocking activity of TPO

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16
Q

Are T3 and T4 hydrophobic or hydrophilic?

A

Hydrophobic

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17
Q

How are thyroid hormones transported in the blood?

A

Bound to serum proteins

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18
Q

How are the half-lives of thyroid hormones prolonged in the blood?

A

By binding to serum proteins

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19
Q

What are the three proteins that bind thyroid hormones in the blood?

A

Thyroxine-binding globulin (TBG)
Albumin
Transthyretin (TTR)

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20
Q

What is the relative abundance of each of the proteins binding thyroid hormones in the blood?

A

Albumin&raquo_space;TTR >TBG

21
Q

What is the relative capacity of each of the proteins binding thyroid hormones in the blood?

A

Albumin&raquo_space;TTR >TBG

22
Q

What is the relative affinitiy of each of the proteins binding thyroid hormones in the blood?

A

TBG >TTR >albumin

23
Q

What is the relative distribution of thyroid hormones’ binding to proteins in the blood?

A

TBG >albumin >TTR

24
Q

What is the major transport protein of T3 and T4 in the blood?

A

TBG

25
Q

Which has a greater affinity for serum binding proteins: T3 or T4?

A

T4

26
Q

Which is more potent: T3 or T4?

A

T3

27
Q

Where is the majority of T3 formed?

A

By target tissues intracellularly by deiodination of T4

28
Q

How do thyroid hormones enter the cell: bound to serum proteins, or free?

A

Free

29
Q

How is T4 activated?

A

Conversion to T3 via deiodination

30
Q

What are the three deiodinases?

A

D1
D2
D3

31
Q

Which deiodinases convert T4 to T3?

A

D1 and D2

32
Q

Which deiodinases inactivate T4?

A

D3

33
Q

Are all deiodinases expressed equally in all target tissues?

A

No, differential expression of deiodinases in different tissues

34
Q

What are the functions of rT3?

A

Binds to extracellular thyroid hormone receptor

Initiates actin polymerisation in astrocytes

35
Q

What are the functions of T2?

A

Inactive

Rapidly degraded

36
Q

How is T4 degraded into T2?

A

T4 > D1/D3 > rT3 > D1/D2 > T2

T4 > D1/D2 > T3 > D3 > T2

37
Q

What are the calorigenic actions of thyroid hormone?

A

Increase O2 consumption of almost all metabolically active tissue
Increase energy substrate uptake and utilisation
Increase energy consumption
Increase cellular respiration rates

38
Q

What are the actions of thyroid hormone on the cardiovascular system?

A

Increase pulse rate
Increase heart weight
Hyperthyroidism can be associated with arrhythmia

39
Q

What is the mechanism of action of thyroid hormone?

A

Increased expression genes of structural/function proteins and proteins involved in thermogenesis
Mitochondrial biogenesis

40
Q

Where is the thyroid hormone receptor (TR) in the cell?

A

Nucleus

41
Q

What does the TR form a dimer with?

A

Heterodimer with retinoid X receptor (RXR)

42
Q

What does the TR/RXR complex bind to?

A

Binds to thyroid responsive element in target gene with direct repeats upstream of transcription start site

43
Q

In the absence of T3, what does the TR/RXR dimer bind to, and what does this mean?

A

Binds to co-repressor complex

Prevents transcription of target gene

44
Q

What does the binding of T3 to TR do?

A

Replaces co-repressor complex with co-activator complex

Initiates transcription of target gene

45
Q

How do the co-activators initiate transcription of the target gene?

A

Many are histone acetyltransferases (HATs)
Neutralise positive charge of histones > DNA dissociates from histones > relaxed nucleosome > transcription of target gene

46
Q

How do co-repressors inhibit transcription of the target gene?

A

Many are histone deacetyltransferases (HDACs)

Return positive charge to histones > associates with DNA > compact nucleosome > no transcription of target gene

47
Q

How does thyroid hormone induce thermogenesis in brown adipose tissue?

A

Increases expression of mRNA for mitochondrial uncoupling protein 1 (UCP 1) in brown adipose tissue

48
Q

What does UCP1 do?

A

Generates heat by dissipating H potential across inner mitochondrial membrane

49
Q

Does thyroid hormone cause stimulation of gene expression alone?

A

No, also causes repression of other genes

MD1 Endocrine (18 decks)

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