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Biochem Winter 2012 > Biochem Hormone Action 1 > Flashcards

Biochem Hormone Action 1 Flashcards

1
Q

What are two systems which regualte internal Milleiu?

A

Nervous System

Endocrine System

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2
Q

What is the Nervous system

A

conducts signals and transmits messages through a fixed structural system

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3
Q

What i s the endocrine system

A

various hormones secreted by specific glands are transmitted as “mobile messages” to act on adjacent and distant tissue

Hromone is derved from a Greek term that means “to aroudn activity”

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4
Q

what are the four odes of Intercellular signaling

A

Endocrine- hormone secretion into the blood

Paracrine- Secretory cell to adjacent target cell

Autocrine- target sites on secretory cell

Juxtacrine- signaling cell to adjacent target cell via cell surface proteins

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5
Q

Describe the conergence of NS and Endocrine system

A

Classic NT (catecholaines, domaine, Ach) are similar ot classic hormones with regards to syntehsis, rlease, tranpsort, and mechanism of action. Catecholamines are NT in one tissue and hormones in another.

EPINEPHRINE0 produced and secreted by postganglionic cells int eh adrenal meduallla

Vasopressin- synthesized int eh hypothalamus and transported by axosn to posterior pituaitry where it is released

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6
Q

Where is Epinephrine produced? where is it secreted?

A

produced and secretedby postganglionic cells in teh adrenal medualla

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7
Q

Where is Vasopressin synthesized? wheat tranports it?

A

synthesized in teh Hypothalamus

Tranported by axons to posterior pituitary where it is released

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8
Q

What are examples of hormone producing cells and its strateically placed location to produce locally high concentratins of hormones

A
  1. Testosterone for Spermatogenesis- this occurs in seminiferous tuubules that are juxtaposed next to Leydig cells, which produce testosterone
  2. Hepatic productio of glucose- regulated by Insluin/glucagon ratio. Pancreas that produces insulin/glucagon is right next to liver
  3. Hypothalamus and Anterior Pituitary are lose in proximity so labile hypothalamic releasing hormones can reach pituitary target via special prota vascular system
  4. Adrenal Cortex produces Cortisol - whcih reaches adrenal medualla by a special portal vascular system. Cortisol is rqd in high amts in teh medulla for the induction of phenylethanolamine-N-mehtyltransferase which is the rate limiting enzyme in catcholaine synthesis
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9
Q

What are the four hormone structures- chemical classes/ (plus one)

A

Peptides

Amino Acids Derivatives

Steroids

Eicosinoids

NO

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10
Q

Peptides

A

synthesized by normal proein synthesis on ribosomes and are susceptible to degradation by proteases

Ex: insulin, glucagon, ACTH, Melanocyte Stimulating hormone

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11
Q

Amino Acid Derivatives

A

These hormones are direclt derived by modification of a baseic amino acid structure but are not peptides like Class #1. The synthesis and metabolism ha e individual characteristics, depending upon the hormone.

Examples include epinephrine made form tyrosine), thyroxine or thryoid hormone (also from tyrosine by iodination)

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12
Q

Steroids

A

All members of this class are dervided from cholesterol by modification of the substituents on teh cholesterol ring sytem and include the large group of primary sex hormones

examples: estradiol, cortisol, calciferl (vit D(, and testosterone

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13
Q

Eicosenoids

A

These hormones are derivatives of unsaturated FA, aracidonic acid and

include prostaglandisn, Leukotrienes, nad THroboxanes

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14
Q

What are different modes of release, activation, and action ?

A

Synthesized and secreted in final form

Modified directly

Modified Indirectly

Specificity

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15
Q

Hormones synthesized and secreted in final form

A

Aldosterone, hydrocortisone, estradiol, catecholamines (epineprhine and NE)

includes many of the steroid hormones as well as others

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16
Q

Hormones that are modified directly

A

Insulin (pro-insulin and partially processed to insulin in the pancreas), glucagon, somatostatn, and the various iodinated derivatives of thyroid hormone (T3, T4),

Produces of POMS (proopiomelanocortin) gene

These hormones are modified either within the cell before secretion or are processed int he target tissue to specific biologically active molecules

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17
Q

Hormones that are modified indirectly

A

By peripheral conersion in non-target tissues

i.e. Thyroxine T4 is converted to T3 in the liver and pituitary. Testosterone to Dihydrotestosterone in secondary sex tisseus
, Vitamin D3 from the skin is converted to 25-hydroxylcalciferol int eh liver and converted to 1,25-dihydroxycholecalciferol in teh kidney

androstendeione is converted to either testosterone or estradiol in fat cells, liver, or skin

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18
Q

Hormone Speciicity

A

Hormones secreteed from very different tissues and having very different cell specificies may have structural similarities

Glycoprotein hormones from the pituitary (TSH, LH, FSH) and form placenta (hCG) are heterodimers consisting of alph and beta subutnits in which alph subunits are IDENTICAL regardless of tissue source, and beta subunits are all different

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19
Q

What kind of hormones have identical ALPHA subunites regardless of tissue sourche

A

GP hormones from pituitary (TSH, LH, FSH) and from placenta (hCG)

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20
Q

How are products of Propiomelanocortin (POMC) processed?

A

Modified directly

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21
Q

what are some of the products of POMC

A 
ACTH (corticotropin),
Beta lipotropin
gamma liptorpin
beta endorphin
Met0enkephalin
Leu-enkephalin
alpha MSh and /or beta MSH

N-terminal fragment

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22
Q

How is insulin modified?

A

By direct modification

Preproinsulin- Proinsulin- Mature Insulin

23
Q

What is C chain of insulin?

A

part of preproinsulin- connects alpha and beta chain

24
Q

What are properties of Hromone-Receptor Systems (3)

A

HIGH AFFINITY- hormones are present at very low concentrations (10^-15 to 10^-9 M) in comparison to other structurally similar molecules (10-5 –> 10-3 M)

HIGH SPECIFICITY- target cells disrciminate between the hormones in small amts and the other molecules present in great excess by cell associated recognition molecuels called RECEPTORS

REVERSIBILITY- Hormones initiate their biologic effects by binding to specific receptors. The hormone-induced actions terminate when the effector dissocieates from teh receptor

25
Q

Features of Hormone-Receptor Systems (4)

A

Label does not effect activity (isotorpic, fluroescent)

  1. Binding must be specific
  2. Binding must be saturable (hyperbola, M-M)
  3. Binding must be at biological concentrations`
26
Q

What are the two functional domains of receptors?

A
  1. Recognition domain- binds the hormone

2. Coupling domain- generates a signal that couples hormone recognition to some intracellular function

27
Q

What is the purpose of the receptor-effector coupling

A

provides firs step in ampliciation of hormonal response.

THis dual purpose is one of the important features that distinguishes the target cell receptor form teh plasma carrier proteinst hat bind hormone but do not generate a signal

Target Cell receptors vs Plasma Carrier Proteins

28
Q

Which has a shorter plasma-half-life (peptide or steroid>

A

Peptide is shorter

Peptide- seconds to minutes

Steroids- hours - all of which have plasma transport proteins

29
Q

What are the different types of Receptor Structures

A

Nuclear (steroid, workis within nucleus)

Plamsa membrane (cell surface)

30
Q

What are different types of Plamsa Membrane (cell surface Rs) (3)

A

Single TM per chain (Insulin)

Serpentine (beta adrenergic)

Ion Channels (acetyl choline, GABA)

31
Q

What type of receptor is an INsulin R? wha does alpha and beta chain do?

A

Single TM (per chain)

Heterodimer (alph2, beta2) linked by multiple disulfide bonds

Alpha subunits bind insulin
Beta subunits transduce signal

32
Q

What type of R is Beta Adrenergic R? Describe its structure

A

Serpentine (7 TM)

Stretches of 18-20 H-phobic aa residues that form aalpha-helix in membrane

Binding site for hormone and there is an intracellular element that interacts iwth other proteins to bring abou tthe desired signal trasduction.

Dopamine, musarineic, seratonin, and light (rhodopsin) R have similar strcutures

Intracellular portion interacts with G protein –> Adenylate cyclase

33
Q

What type of recpor is Acetylcholin R and GABA R?

A

Ion channels

34
Q

What are examples of Intraceullular (Nuclear) Receptors

A

Estrogen, Progesteroen, Glucocorticoid , Thyroid

Has a Transcriptional activation Region

35
Q

In PM receptors, where is the C domain? N domain? Extracellular or intracellular?

A

N= extracellular domain

C= intracellular cystoplasmic domain

36
Q

What is signal transductino by Insulin Receptor

A

by tyrosing kinase component of cytoplasmic protion of beta subunit (intracellular domain)

37
Q

What is IGF I R?

A

Receptors for insulin-like growth factor I (IGF I) and epidermal growth factor (EGF) are similar to insulin R in funcitonal and structural organization of the recetpro

ave ability to funciton as both an autophosphorylating TK and a Tk that phosphyroates other ptoeins

38
Q

What are examples of steroid hormone receptors

A

Intracellular, not membrane bound

Glucocorticoid R is most well characterized

Thyroid horone R and Reitnoic acid R are similar

39
Q

What type of recepor is Glucocorticoid? What are the three functional domains of Glucocorticoid

A

Steroid R (similar domains in retinoid and thyroid Hormones as well)

  1. Hormone binding domain in carboxy terminal end of molecule
  2. DNA binding domain that is adjacent ot hormone indign region
  3. Activation domain, loacated int eh amino terminal half of the molecule
40
Q

Describe Acetycholine R (nicotinic)

A

Ionic R

Consists of 4 subunits int he configuration of alpha2, beta, gamma, delta

Two alpha subunits bind Ach

Separate and specific regions of alpha subunits are invovled in formaiton of TM ion channel , which perofem major fucntions of Ach R

41
Q

What is the muscarinic Ach R

A

7 TM domain,

G-protein coupled R (similar to beta-adrenergic R)

42
Q

What are the two types of Gluamate R

A

Ionotropic
ligand gated ion channels;
tetramer or pentamer
4 or 5 TM regions each

  1. Metabotropic ( 7 TM)
    GPCR (similar to beta adrenergic)
43
Q

How can you distinguish between the ionotropic and metabotropic R of Glutamate NT

A

by inhibitors that are specific for ionotropic or metabotropic R

44
Q

GABA Receptor

A

NT sensitive ion channel with the subunit structure alpha6, beta3, gamma1, delta 2 with multiple TM regions

the NT gamma-aminobutryic acid, has a R which is als a tetramer of chains with 4 TM domains that acts as a gated ion channel

45
Q

What are Ecosanoids

A

biological activity hs characterisitcs of receptor mediated response.
R not isolated.

Eicosanoids have exceedingly short half liffe which has made characterizaton and isoalteon of receptor very difficult

46
Q

Describe the foling of the beta adrenergic R (similar for all 7TM , serpentine R)

A

the 7 helix motif is a commmon feature of TM rR that activate GP

note two N linked oligosccharide chains on the extracellular side.

loop on teh cytosolic cside interacts with GP and is regulated by phosphoyrlation by BARK and arrestin bidnign.

47
Q

ionotropic vs metabotropic

A

Ionotropic- ligand gated ion channel

Metabotropic R- 7 TM, GPCR

48
Q

What are Agonists vs partial agonists

A

Agonists fully occupy R and elicit maximal possible biolgoical effect, although different concentrations may be required

Partial agonists fully occupy teh R but cannot, regarldess of concnetrations , elicit a maximial biological response.

49
Q

What are antagonists?

A

can fully occupy receptor but no biolgoical response can be elicted.

To the extend that partial agonists can occupy the receptor and prevent the bindng of true agonist, and that the resulting biolgoical response will be less than mexmail, partila agonist when present iwth true agonists are sometimes refered to as partial antagonists.

50
Q

What will happen to binding curve if full atangonist is added at a constant concentration.

A

Binding curve will shift to the right, amt depending on concentration of the antagonist

51
Q

How are Receptors Regulated

A

Down regulation (desensitive)

Covalent modificatio of R

Up Regulation

52
Q

Down regulation

A

loss of receptor number from PM by internal sequenstration (internalization) of R

This change in R number results in desensitization of biolgoical response to addition of more agonist. Removal of agonist resutls in the return of R to cell surface and restoration of hormonal sensitivity

53
Q

What tyeps of hormones down regulate their R

A 
Insulin
Glucagon
TRH
GH
H
FSH 
catecholamines

Biochem Winter 2012 (10 decks)

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