2.4 Intro To Hormones Flashcards

1
Q

What are hormones?

A

Chemical messengers synthesized by specific endocrine glands which are directly secreted to their distant target organs via the bloodstream.

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2
Q

Classification of hormones in terms of chemical composition, solubility properties, location of receptors, nature of intracellular messenger.

A

Chemical composition
>Amino acids
>Polypeptide
>Steroids

Class I
Solubility: hydrophobic/lipophilic - can penetrate the membrane

Location of receptors: Intracellular (cytoplasmic or nuclear)

Nature of intracellular messages: formation of hormone-receptor complex

Class II
Solubility: Hydrophilic/Lipophobic

Location of receptors: Extracellular (membrane-bound)

Nature of intracellular messages: Hormone is the first messenger; 2nd messengers produced upon binding to their receptor

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3
Q

Which hormones are derived from Tyrosine?

A

Triiodothyronine (T3), Epinephrine, Norepinephrine, Thyroxine/tetraiodothyronine (T4)

TENT

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4
Q

Which hormones are derived from Cholesterol?

A

Progesterone

Aldosterone

Calcitriol

Cortisol

(Beta-)Estradiol

Testosterone

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5
Q

How many amino acids:

  1. TRH
  2. ACTH
  3. Vasopressin (Antidiuretic Hormone)
  4. Somatostatin (GHRIH)
A
  1. 3
  2. 29
  3. 9
  4. 14
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6
Q
Class I:
>Solubility
>Chemical composition
>Transport proteins 
>Intracellular messenger
>Examples
A
Transport Proteins (increases half-life):
1. Steroid Hormones: Transcortin, ABP, SHBG, Albumin
  1. Thyroid Hormones:
    TBG, TBP

Examples:
GREAT CaMP

GCs
Retinoic Acid
Estrogens
Androgens
Thyroid Hormones

Calcitriol
Mineralocorticoids
Progestin

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7
Q

Kinetics of hormone receptor interaction. What is KD? Bmax?

A

R.H —k1—> R+ H

R.H

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8
Q

Functional domains of a cell-surface receptor?

A
  1. Extracellular/ligand binding domain
    - where hormone binds to receptor
    - found on extracell side
  2. Transmembrane domain
    - consists of several helices of hydrophobic aa’s that are comfortable living in the basically phospholipid layered membrane
    - to anchor receptor to cell membrane/plasma membrane
  3. Cytoplasmic/intracellular domain (effector region)
    - attached to certain molecules that will produce the 2nd messengers
    - Thus, effective/effector region of receptor
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9
Q

Variations of cell-surface receptors?

A
  1. Single-pass
    - Integral membrane protein/™ protein (spans membrane once)
    - Simple single pass membrane as exemplified by EGF receptor
  2. More than 1 subunit
    - More than 1 subunit
    - e.g. Insulin receptor (has alpha and beta subunits)
  3. Heptahelical
    - E.g. Beta-Adrenergic receptor utilized by epinephrine
    - Consists of 7 spanning alpha helices; criss-crossing membrane 7 times like snake
    - aka serpentine receptor
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10
Q

What is a rhodopsin?

A
  • Photoreceptor found in the rods and cons of the retina
  • Can’t see without this receptor
  • Heptahelical; GPCR
  • Stimulus: Light/Photon
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11
Q

General Features of Cell Signaling by Chemical Messengers?

A
  1. SECRETION
    - through proper stimulus
  2. RECEPTOR BINDING
  3. RESPONSE/SIGNAL TRANSDUCTION
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12
Q

For Class II, give two usual effector molecules?

A
  1. AC

2. PLC

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13
Q

Major cell surface receptors?

A
  1. Heptahelical receptors
  2. Receptors that are kinases or bind kinase
    -Tyrosine kinase receptor
    >Insulin/Growth factor -> dimerize -> P -> SH2
    >Homodimeric receptor

-JAK-STAT receptors
>Heterodimeric receptor
>Cytokine/Growth hormone -> dimerization of GHr-> (P) by Janus Kinase -> STAT

-Ser-Thr Kinase receptors
>Heterodimeric receptor
>Cytokine dimer/TGF-Beta binding -> P of Ser tesidues in cyt domain -> message transmitted to Smad

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14
Q

Synthesis and Degradation of cAMP

A

ATP: 3 Phosphate groups attached to 5’ carbon of ribose sugar; adenine attached to 1’ C

In the presence of AC found in PM -> ATP is converted to cAMP
PPi is released and in the presence of pyrophosphatase, pyrophosphate is cleaved in 2 molec of inorganic phosphate -> cleavage is enough to drive rxn forward

Once you don’t need cAMP, inactivated to AMP by phosphodiesterase

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15
Q

cAMP as 2nd messenger of Epinephrine

A

Beta-adrenergic receptor (found in postganglionic fiber in the heart, kidney, liver, lungs, brain)

Epineph binds to receptor forming R-H complex -> activates G protein -> Activate AC -> synthesize cAMP from ATP -> cAMP will convert inactive cAMP-dependent PK to active state -> kinase acts on glycogen synthase (major enzyme responsible for glycogenesis), decrease activity of glycogen synthase by phosphorylation -> glycogen synthase becomes phosphorylated = inactive state

-> cAMP-dep PK will also try to increase activity of a phosphorylase kinase = phosphorylation = activated -> Phosphorylase kinase will activate glycogen phosphorylase (for glycogen lysis) -> promote glycogen degradation -> glucose levels increased

= blood glucose levels increased

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16
Q

cAMP as 2nd messenger of glucagon

A

In metabolism, generally, anabolic hormones when phosphorylated are inactivate; and catabolic hormones are activated

Glucagon is secreted by pancreatic alpha cells in the presence of low blood glucose levels (starvation) -> Glucagon binding to receptor -> activated GTP -> AC activated -> increased cAMP -> cAMP activated cAMP-dependent PK -> PK will decrease activity of PFK-2 = low levels = low Fructose-2,6-bisphosphate -> lack of allosteric activation of glycolysis -> suppressed glycolysis

—> PK -> increases activity of Fructose bisphosphatase-2 (P) -> decrease levels of Fructose-2,6-BP -> allosterically activates enzymes of gluconeogenesis

Combined effect of decreased glycolysis and inc gluconeogenesis in the presence of glucagon mediated by G proteins and cAMP = to restore normal blood glucose levels

17
Q

Galpha,i hormones/signaling molecule

A

Melatonin, ADP, Insulin, Epinephrine (alpha 2 receptor)

18
Q

What happens in…

  1. /Vibrio cholera/ infection?
  2. /Bordetella pertussis/ infection?
  3. Benign Thyroid Adenomas
  4. Bronchospasm in asthma due to Ca2+-elevating levels
A
  1. Vibrio: modify G alpha s = no inherent GTPase activity
  2. Bordetella: modify G alpha, i = permanent activation of G proteins
  3. Mutant TSHr: modifies G alpha s = can’t hydrolyze GTP … overproduction of TH = hyperthyroidism
  4. Epinephrine-induced synth of cAMP = Relaxation of bronchial smooth ms = Alleviation of bronchospasm
    * Salbutamol, Theophylline, Aminophylline - for bronchial asthma therapy
19
Q

cAMP: PKA:: cGMP : ______

A

PKG

20
Q

Nitroglycerin/Glycerol Trinitrate in cGMP pathway?

A

Nitroglycerin/Glycerol trinitrate rapidly metabolized to NO in the body —> Activated Guanylyl Cyclase —> Increased cGMP —> Relaxation of smooth ms cells in bvs —> Vasodilation —> Improved O2 delivery to heart —> Alleviation of angina pain

21
Q

Mechanism of Viagra?

A

Viagra/Sildenafil citrate —> inhibits cGMP phosphodiesterase —> increased cGMP in vascular smooth ms cells of penis —> muscle relaxation and vasodilation —> Sustained erection

22
Q

How do we see?

A

Light/photon activates rhodopsin —> activates phosphodiesterase —> decreased cGMP (to GMP) —> Na+ cannot come across CM of rods and cons —> hyperpolarization of rods and cons of membranes —> release of glutamate (NT) —> Glutamate will transmit signal to visual center of adrenal cortex

23
Q

PIP2 2nd messenger scheme?

A

Synthesized PIP3 that synth DAG that synth Ca2+ as remaining 2nd messenger

Hormone binding to receptor in CM -> activate a Gq -> activate membrane-bound PLC -> PLC convert PIP2 (phosphatidylinositol-4,5-bisphosphate) to IP3 (Inositol triphosphate) and DAG (diacylglycerol) by cleavage -> IP3 is soluble and can easily pass through cytoplasm stimulate release of Ca2+ from the lumen of ER in the cytoplasm (cytoplasmic reticulum) increasing levels of Ca2+ there -> Ca2+ combines with calmodulin forming a Ca-Calmodulin complex -> complex activates a cytoplasmic kinase enzyme which phosphorylates a number of enzyme in the target cell

Ca2+ - 2nd messenger from PIP2; many effects

DAG - cannot escape out of membrane but easily diffuses to CM -> stimulate PKC -> PKC will regulate the entry and exit of Ca2+ ions to your calcium channels present in CM s.t. decreased level of Ca2+ intracellularly, IP3 and DAG come to restore serum calcium levels inside the cell.

PIP2 produces IP3, Ca2+, and DAG as certain messengers

24
Q

Conversion of Phosphatidylinositol to IP3?

A

PI — PI kinase —> PIP2 —PLC —> IP3 + DAG

25
Q

2nd messenger of insulin

A

Tyrosine Kinase