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Metabolic endocrinology > section 2 > Flashcards

section 2 Flashcards

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

A
23
Q

What type of receptors is the most numerous class

A

G-protein couples receptors

24
Q

How many trans membrane alpha-helices has GPCR

A

7

25
Q

Examples of endocrine and non-endocrine signals acting through GPCR

A

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
Q

Does one hormone is specific to one G-protein?

A

No, it can use more and also G protein use may change during development and also concentration of hormone

27
Q

2 types of tyrosine kinase coupled receptors

A

Receptors with an intergrated (intrinsic) kinase activity

Receptors that recruit a kinase

28
Q

insulin receptor is in what class of receptors

A

Intrinsic tyrosine kinase activity

29
Q

How many parts insulin receptor has

A

Hetero-tetrameric (2 alpha and 2 beta held together by S-S bonds)

30
Q

What domain alpha or beta has a transmembrane

A

β subunit about 618 a.a.: Ectodomain
193 a.a., transmembrane domain 23
a.a., cytoplasmic domain 402 a.a.

31
Q

Where the most of insulin receptors are

A

In adipocytes and hepatocytes

32
Q

Insulin receptor has a homology with what receptor

A

IGF-1

33
Q

Sequence of events after insulin binding

A

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
Q

Describe Insulin receptor signaling through MAPK pathway

A

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
Q

Insulin receptor signaling through PIP3

A

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
Q

Characteristics of receptors that recruit tyrosine kinase activity

A

4 alpha helices and homology of the ectodomain (hormon binding site)

37
Q

Best known receptors of recruited tyrosine kinase activity

A

Growth hormone, prolactin, leptin

38
Q

GH signaling pathway

A

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
Q

3 branches of phosphorylated JAK activity

A

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
Q

Describe JAK-STAT pathway

A

Binding of the hormone cross-liks adjacent receptors and jaks cross-phosphorylate each other on tyrosines and then phosphorylate the receptor on tyrosines

41
Q

What does it mean non-classical peptide hormones and examples

A

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
Q

Neurotransmitters examples that are amino acid derivative

A

Neither a peptide or hormone, but derived from AAs

Melatonin, serotonin, histamine

43
Q

Examples of lipid hormones with memebrane receptors

A

Eicosanoids never classified as steroids, because they are using cell membrane receptors (GPCRs)

And steroids are using nuclear receptors

44
Q

What 4th category is considered non-classical hormones and through what receptors they function

A

Lactate, ketone bodies, succinate, FAs ,etc.

GPCRs

45
Q

To what receptors steroid and thyroid hormones bind

A

To a family of intracellular receptors which are structurally related adn founf in the cytoplasm or nucleus

Nuclear receptor family

46
Q

Nuclear receptors function as ____ and how fast they give the response

A

Nuclear receptors and function as transcription factors

Response is slow since transcription and translation takes time,as well as post-translational modifications

47
Q

Name ligands for nuclear receptors from classical hormones class, vitamins, metabolic intermediates and products

A

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
Q

Mechanism regulating ligans levels

A

Precursor availability

Synthesis

Secretion

Activatione (prohormone->active hormone)

Deactivation (active hormone->inactive hormone)

Elimination ( hepatic, renal clearance)

49
Q

Describe the pathway of nuclear receptor signalling mechanism

A
50
Q

3 domains that all nuclear receptors will have

A

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
Q

sequences of nuclear DNA binding domains

A

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
Q

Explain chromatin immuniprecipitation (ChIP) sequencing

A
53
Q

Factors modulating receptor activity in different tissues

A

Metabolic endocrinology (9 decks)

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