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Metabolic endocrinology > section 2 > Flashcards

section 2 Flashcards

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1
Q

Whay else target proteins can do

A

Give the feedback to the receptor

Can be activation or inhibition of this protein, this will lead to a feedback of reaction and will go to the beginning of the cascade ( often to receptor protein ) inhibitiin ghtem or internalizing them

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2
Q

What can happen to the signal during transmission

A

Exponential amplification during transmission

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3
Q

Based on the signal receptor, pathways can be divided into 2 main classes

A

Pathways with cell-surface receptors

Pathways with intracellular receptors

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4
Q

Basic strucutre of a cell surface receptor

A

Extracellular domain with NH2 end, whic have disulfide bond and glycosylation

Hydrophobic transmembrane domain

Cytoplasmic domain with Co2H

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5
Q

What AAs make transmembrane domain and how many of them are needed for that

A

20-25 AAs are needed to cross membrane once

Hydrophobic AAs (ala, Ile,Leu,Met,Phe,Val,Pro,Gly)

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6
Q

Ectodomain (NH2) is often rich in ___ for S-S bonds for folding

A

Cysteine

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7
Q

What secondary structure transmembrane has

A

Alpha-helix

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8
Q

What does it mean that 3 domains of the receptor are interchangeable

A

you can put an extracellular part of the receptor on the other receptor of the same strucutre and it will work fine

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9
Q

If the receptor have only an ectodomain what it can do

A

It can serve as a buffer system, binding to the hormone in the circulation and increasing its half life

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10
Q

What can be the result of cleaved ectodomain in the circulation

A

The ectodomain cleaved frim the TSH receptor may induce antibodies which binds to the receptor and mimic TSH action ->hyperthyroidism in Grave’s disease

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11
Q

What will happen to cytoplasmic domain of the receptor upon binding of hormone to the ectodomain

A

conformational change or indicing the intrinsic enzymatic acitvity or recruitng someone

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12
Q

Many signaling proteins are activated by phosphorylation at the AAs:

A

Serine, threonine and tyrosine on OH group

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13
Q

Who is the phosphate donor in phosphorylation

A

ATP

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14
Q

Phosphorylation causes

A

Conformational change of the protein

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15
Q

What signaling proteins that are activated by phosphorylation will perform signal amplification

A

Kinases

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16
Q

Phosphorylation can be reversed by

A

Phosphatases

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17
Q

What AAs are phosphorylated usually

A

Serine and threonine

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18
Q

When tyrosine is usually phosphorylated and what is their role

A

In the beginning of the cascade

They serve as a docking sites for down signalling rather than further phosphorylation

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19
Q

What is the name for tyrosine domains that will be phosphorylated

A

SH2 and SH3 domains

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20
Q

3 major types of cell surface receptors

A
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21
Q

What happens to GPCR upon binding of the signal

A

G alpha is released and then it goes to adenylyl cyclase or other enzyme to activate it

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22
Q

5 types of Galpha subunits

23
Q

What type of receptors is the most numerous class

Study These Flashcards
A

G-protein couples receptors

24
Q

How many trans membrane alpha-helices has GPCR

25
Examples of endocrine and non-endocrine signals acting through GPCR
Many receptors of non-endocrine signals also act via G-proteins. Examples: glutamate (neurotransmitter), thrombin, odorants and photoreceptors -Examples of endocrine hormone receptors are TRH, GnRH, TSH, LH, FSH, ACTH, GHRH and oxytocin
26
Does one hormone is specific to one G-protein?
No, it can use more and also G protein use may change during development and also concentration of hormone
27
2 types of tyrosine kinase coupled receptors
Receptors with an intergrated (intrinsic) kinase activity Receptors that recruit a kinase
28
insulin receptor is in what class of receptors
Intrinsic tyrosine kinase activity
29
How many parts insulin receptor has
Hetero-tetrameric (2 alpha and 2 beta held together by S-S bonds)
30
What domain alpha or beta has a transmembrane
β subunit about 618 a.a.: Ectodomain 193 a.a., transmembrane domain 23 a.a., cytoplasmic domain 402 a.a.
31
Where the most of insulin receptors are
In adipocytes and hepatocytes
32
Insulin receptor has a homology with what receptor
IGF-1
33
Sequence of events after insulin binding
Autophosphorylation of intracellular domain of receptor Docking and phosphorylation of IRS-1 and IRS-2 (insulin receptor substrate) Activation of two major signal pathways
34
Describe Insulin receptor signaling through MAPK pathway
Initiation: receptor and ligand interaction, insulin binds to insulin receptor The portion that is blue ( cytoplasmic domain - inside the cytoplasm) gets phosphorylated This phosphorylation leads to another phosphorylation of insulin receprtor (IRS-1) IRS-1 acts as a docking protein( adaptor ) for GRB-2 , a cascade of adaptor proteins They come together and form a complex of proteins MEK gets phosphorylated on 2 serines MEK phosphorylates ERK on Thr and Tyr Phosphorylated ERK moves into the nucleus, where ( as a kinase) activate transcription factors SRF and Elk 1-\> transcription-\> protein
35
Insulin receptor signaling through PIP3
Ligand binding to the receptror, and it phosphorylayes IRS-1 IRS-2 acts as a docing protein IRS-2 phosphorylates allows PI3K to connect PI3K converts PIP2 to PIP3 ( not a cleavage mechanism like in GPCR) PIP3 allows for doking PKB, which is activated by phosphorylation Protein kinse B( PKB) phosphorylate GSK3 , inactivating it , now GS kinase cannot add phosphate to inactivate GS, so synthesize of glycogen occurs ( REMOVAL OF INACTIVATOR) PKB helps in opening GLUT4 and helps in bringing glucose inside the cell
36
Characteristics of receptors that recruit tyrosine kinase activity
4 alpha helices and homology of the ectodomain (hormon binding site)
37
Best known receptors of recruited tyrosine kinase activity
Growth hormone, prolactin, leptin
38
GH signaling pathway
GH binds to the receptor 1. it forces to bring the second part of the complex, which together can recruit JAK-2 Recruitment of JAK2: phosphorylates itself, the receptor and other proteins
39
3 branches of phosphorylated JAK activity
Branch 1: Activation of the transcription regulatory proteins, STAT (4 isoforms) ( usually stuck near membrane, but as soon as it is phosphorylated can go inside the nucleus) v Branch 2: Activation of the MAPK pathway (as insulin, but JAK2 plays the role of IRS1) v Branch 3: Activation of PI3K pathway
40
Describe JAK-STAT pathway
Binding of the hormone cross-liks adjacent receptors and jaks cross-phosphorylate each other on tyrosines and then phosphorylate the receptor on tyrosines
41
What does it mean non-classical peptide hormones and examples
IGF is a peptide hormone, though water soluble, it is carried in the circulation bound to a carrier protein Adipokines: leptin is also example of this group
42
Neurotransmitters examples that are amino acid derivative
Neither a peptide or hormone, but derived from AAs Melatonin, serotonin, histamine
43
Examples of lipid hormones with memebrane receptors
Eicosanoids never classified as steroids, because they are using cell membrane receptors (GPCRs) And steroids are using nuclear receptors
44
What 4th category is considered non-classical hormones and through what receptors they function
Lactate, ketone bodies, succinate, FAs ,etc. GPCRs
45
To what receptors steroid and thyroid hormones bind
To a family of intracellular receptors which are structurally related adn founf in the cytoplasm or nucleus Nuclear receptor family
46
Nuclear receptors function as ____ and how fast they give the response
Nuclear receptors and function as transcription factors Response is slow since transcription and translation takes time,as well as post-translational modifications
47
Name ligands for nuclear receptors from classical hormones class, vitamins, metabolic intermediates and products
Classical hormones: thyroid, estrogen, testosterone, progesterone, aldosterone, cortisol Vitamins: vitamins D and A (cis and trans forms) Metabolic intermediates: FAs,oxysterols,bile acids,heme,phospholipids, xenobiotics
48
Mechanism regulating ligans levels
Precursor availability Synthesis Secretion Activatione (prohormone-\>active hormone) Deactivation (active hormone-\>inactive hormone) Elimination ( hepatic, renal clearance)
49
Describe the pathway of nuclear receptor signalling mechanism
50
3 domains that all nuclear receptors will have
DNA binding doamin(a/b) Nuclear localization signal( the sequence so the protein comes from the cytoplasm into the nucleus) (C/d) Ligans binding domain (LBD) (E)
51
sequences of nuclear DNA binding domains
Steroid hormones funciton as homodimers and inward direction sequence The middle part of the sequence is the most important RXR heterodimers in direction following each other
52
Explain chromatin immuniprecipitation (ChIP) sequencing
53
Factors modulating receptor activity in different tissues

Metabolic endocrinology (9 decks)

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