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Biochemistry - Sarah > Hormones > Flashcards

Hormones Flashcards

1
Q

Agonist

A

drug that binds to a receptor and mimics the normal ligand action (e.g. isoproterenol acts like adrenaline at beta adrenoreceptors - treat bradycardia, slow heart rate)

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2
Q

antagonist

A

prevents the action of a hormone

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3
Q

Clinical uses of hormones

A 
Insulin to treat diabetics
Anticancer therapies (block testosterone action for prostate cancer with flutamide (prostate cancer is testosterone responsive))(block estrogen action for breast cancer with FASLODEX (fulvestrant) an estrogen receptor antagonist (competes for binding site))
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4
Q

Types of hormones

A

endocrine - made in one tissue and travel to target organ, paracrine - made in a cell and travel short distance, autocrine - made and functions in same cell (or nearby)
Peptide - includes growth factors, amino-acid derived hormones, usually water soluble, bind cell surface receptors
Steroid - membrane permeable, bind intracellular receptors

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5
Q

Endocrine hormones

A 
insulin is an example
made in one tissue
travel to target organ through blood
receptor-expressing cells
Tend to be stable, larger amounts, longer half-life
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6
Q

Paracrine hormones

A 
Acetylcholine is an example
Made in a cell
Travels a short distance
Bind receptors on neighboring cells
Smaller amounts, shorter half life
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7
Q

Autocrine hormones

A

Nitric oxide is an example
Made and functions in same cell or near by
small amount, short half life

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8
Q

Peptide hormones

A

Includes growth factors, amino-acid derived hormones
Usually water soluble, bind cell surface receptors
Insulin, glucagon, adrenocorticotropin hormone (ACTH) are examples

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9
Q

Steroid hormones

A

Membrane permeable (lipid soluble)
Bind intracellular receptors
Adrenal hormones: Cortisol (glucocorticoid), aldosterone (mineralcorticoid)
Sex and Progestational hormones: 17 beta estradiol (estrogen), testosterone (androgen), and progesterone (progestin) are examples
Derived from cholesterol

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10
Q

Things to remember about hormones that bind to cell surface receptors

A

The binding is tight
It is swift and reversible
Receptor specificity and affinity for hormone is high

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11
Q

Examples of basic signal transduction mechanisms include:

A
  1. Receptor coupled to adenylate cyclase (cAMP)
  2. Receptor kinase activity (phosphorylation)
  3. Receptor coupled to hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2)
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12
Q

Endogenous production of insulin can be detected by:

A

presence of C-peptide

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13
Q

Human insulin analogs

A

Lispro and Aspart (short-acting and rapidly absorbed), Glargine (long-acting, peakless, low rates of hyperglycemia)

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14
Q

Insulin signaling

A

Tyrosine kinase receptor
phosphorylates itself and IRS
allows binding of proteins with SH2 domains (Grb2 and PLCgamma)
activates PI3 kinase
Activates protein kinase B (also called Akt)

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15
Q

Epinephrine receptors

A

Epinephrine binds alpha-adrenergic receptors and beta-adrenergic receptor
In the liver, epinephrine acts through G proteins and PIP2 signaling (IP3 causes release of calcium)
In muscle, epinephrine acts through cAMP signaling

Phosholipase C is involved, as well as Protein kinase C. Calmodulin-dependent protein kinase and phosphorylase kinase are activated, which inactivate glycogen synthase and activate glycogen phosphorylase

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16
Q

Glucagon effects

A

acts through cAMP
Glucagon leads to inhibition of glycogen synthase
uses G protein, cAMP, Active protein kinase A
Examples of second messengers are Calcium, cAMP, diacylglycerol, and inositol triphosphate
(Epinephrine and glucagon work in similar ways)

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17
Q

Transport of steroids

A

Plasma albumin is a nonspecific carrier
Transcortin (aka cortico-steroid binding globulin) transports cortisol and corticosterone
Sex-hormone binding globulin carries testosterone and 17-beta estradiol

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18
Q

All steroid hormones are synthesized from __.

A

cholesterol

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19
Q

Hormone synthesizing enzymes are activated by __.

A

FSH, ACTH, and LH

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20
Q

ACTH, FSH, and LH activate ___.

A

hormone synthesizing enzymes
A cholesterol esterase to produce rapid supply of cholesterol
Synthesis of LDL receptors

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21
Q

ACTH activates ____.

A

cortisol synthesis

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22
Q

Cortisol synthesis is activated by ___.

A

ACTH

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23
Q

LH activates ___.

A

Testosterone synthesis

24
Q

Testosterone synthesis is activated by ___.

A

Lutenizing hormone (LH)

25
Q

FSH activates ___.

A

Estrogen synthesis

26
Q

Estrogen synthesis is activated by ___.

A

FSH (follicle stimulating hormone)

27
Q

____ are key in steroid hormone synthesis.

A

Hydroxylation reactions

28
Q

Hydroxylation reactions of cholesterol use ___.

A

“mixed function oxygenases” that all have a similar mechanism with multi-enzyme complexes that use molecular oxygen and NADPH

29
Q

Regulation of steroid hormone synthesis

A

The primary regulatory enzyme is 20,22-lyase (CYP11A)

activated by phosphorylation

30
Q

20,22-lyase (CYP11A)

A

the primary regulatory enzyme of steroid hormone synthesis
Activated by phosphorylation
Mitochondrial enzyme
aka 20,22-desmolase or cholesterol desmolase

31
Q

desmolase

A

enzyme that catalyzes the cleavage of C-C bond in a subtration with formation of 2 products by a process other than hydrolysis

32
Q

Biosynthesis of steroid hormones overview

A

cholesterol desmolase (CYP11A) converts cholesterol to pregnenolone. This is converted to progesterone and androstendione. Progesterone is converted to deoxycorticosterone, which is converted to aldosterone (zona glomerulosa, using CYP11B2) or cortisol (zona faciculata using CYP21A2). Androstendione is converted to estron (using aromatase/CYP19) or testosterone (using 17 beta-hydroxysteroid dehydrogenase). Estron or testosterone can be converted to estrogen using aromatase CYP19 (testosterone) or 17beta-hydoxysteroid dehydrogenase (estron).

33
Q

Steroid hormone diseases

A

Congenital adrenal hyperplasia or aldosterone synthase deficiency

34
Q

congenital adrenal hyperplasia

A

95% due to steroid 21-hydroxylase deficiency (CYP21A2)
Symptoms include vomiting and dehydration for severe deficiency, to infertility in mild deficiency)
Reduces aldosterone and cortisol production
Diagnosis based on elevated 17 hydroxyprogesterone

35
Q

Aldosterone synthase deficiency

A

aldosterone stimulates sodium reuptake. Hydroxylation of deoxycorticosterone at C11b and C18 required to form aldosterone. CYP11B2 required for all reactions. Enzyme deficiency causes electrolyte imbalance, vomiting, dehydration in infancy

36
Q

Mechanisms of Steroid Hormone action

A

Steroid hormones:
pass through the cell membrane (hydrophobic)
bind specific intracellular receptor (cytoplasmic or nuclear receptor) (hormone dependent transcription factor)
Hormone/receptor complexes go to nucleus (bind regulatory DNA sequences)(Hormone-responsive elements, HRE, or SRE (steroid RE))
Turn transcription of specific genes on or off

Steroid hormone effects:
can last for relatively long periods (hours to days)
Influence growth and differentiation of specific tissues

37
Q

Steroid hormone receptors are ___ factors.

A

transcription (most are activated by dimerization. Large family of receptors that bind to hormone response elements in DNA)

38
Q

DNA binding domain

A

two zinc fingers, side by side
Each has a peptide loop with a zinc atom at the core
one binds DNA (major groove)
other lets receptors dimerize
conserved sequence
allows receptor to sit on the surface of the DNA double helix

39
Q

How production of cortisol is activated and controlled

A

Stress response
Glucocorticoide
Body stress stimulated hypothalamus to produce CRH (Corticotropin-releasing hormone)
Activates anterior pituitary to produce ACTH (adrenocorticotropin hormone)
Activates adrenal cortex to produce cortisol
acts on fibroblasts and hepatocytes (etc.)

Cortisol inactivates production of CRH and ACTH

40
Q

Functions of cortisol

A
  1. metabolism: increased degradation of muscle to provide amino acids for gluconeogenesis; increased lipolysis in adipose tissue
  2. Immunosuppressive
41
Q

How do glucocorticoids related to patients in critical care?

A

Critical care patients often have elevated glucocorticoid levels due to stress or treatment with methylprednisone or dexamethasone to reduce inflammation (they inhibit phospholipase A). These increase blood glucose levels by increasing gluconeogenesis at the same time as tube or IV feedings. ICU patients have frequent blood glucose monitoring.

42
Q

Cushing Syndrome

A

Exogenous (90%):
Due to over administration of excess amounts of glucocorticoids (prednisolone, dexamethasone)

Endogenous (10%):
Most cases are caused by ACTH-secreting pituitary adenoma

“moon face”, truncal obesity, dorsocervical fat pads (buffalo hump)

43
Q

ACTH stimulation of cortisol synthesis

A
  1. G protein coupled receptor
  2. cAMP production by adenylate cyclase
  3. Protein kinase A activation
  4. Cholesterol released into mitochondria
44
Q

Thyroid hormone pathway

A

Hypothalamus produces TRH (thyroid releasing hormone), which activates the Anterior pituitary to produce TSH, which activates the thyroid to make T3 and T4

45
Q

Thyroglobulin

A

660kDa protein that has 115 Tyr residues that can be modified by iodide (oxidized iodine) to form monoiodotyrostine (MIT) or diiodotyrosine (DIT). These are coupled to form T4 or T3

46
Q

Low levels of T3 and T4 activate ___.

A

Synthesis of TSH

47
Q

Thyroid hormone release

A

Iodine is pumped into thyroid follicular cell
Tyrosine residues iodinated by thyroid peroxidase in colloid of thyroid
TSH stimulates endocytosis, degradation of thyroglobulin by proteases and release of T4, T3
Most plasma T3 and T4 are bound by thyroxin-binding globulin
Thyroid hormone act through nuclear receptors to modulate gene transcription

48
Q

What protein iodinates tyrosine residues?

A

thyroid peroxidase

49
Q

Most plasma T3 and T4 are bound by ___.

A

Thyroxin-binding globulin

50
Q

Thyroid hormones act through nuclear receptors to modulate ___.

A

gene transcription

51
Q

Possible cause of hypothyroidism

A

iodine deficiency

52
Q

How is thyroid hormone related to thermoregulation?

A

Through release of norepinephrine stimulating uncoupling protein (thermogenin) in brown fat and permeability of muscle to sodium. Increases sodium, potassium ATPase and ATP turnover. Longer term increases enzymes of fuel oxidation.

53
Q

Hyperthyroidism is associated with ___.

A

Insulin resistance (as well as increased hepatic gluconeogenesis and rapid gastrointestinal glucose absorption)

54
Q

Subclinical hypothyroidism

A

Elevated TSH with no symptoms

55
Q

True or False: Higher cholesterol values can be caused by hyperthyroidism.

A

False, Hypothyroidism can cause higher cholesterol values, though whether hyeprthyroidism causes it I am actually not sure.

56
Q

Test for TPO antibodies

A

Test for thyroid peroxidase antibodies can be used to diagnose autoimmune cause of hypothyroidism.

Biochemistry - Sarah (12 decks)

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