TBL-7 Protein Modification and a Signaling Introduction Flashcards

1
Q

Glycosylation and example

which one is our focus here

A

attach a sugar to an N or O of peptide

ex:

(1) Asparagine-linked (N-linked), covered later
(2) Serine/threonine-linked (O-linked) , covered later

(3) GPI Anchors

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2
Q

example of pathogen that uses glycans to gain cell entry

A

RBD (covid 19) recognizes N322 glycan on ACE2 (receptor) in lung

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3
Q

Innate immune system response

A

Innate immune system

distinguishes self from non-
self through the activity of pattern recognition receptors.

these immune cells have glycan-type toll-like receptors TLC-4 that recognize lipopolysaccharides found on the surface of
gram-negative bacteria and not in humans

induces inflammatory response proteins, phagocytosis

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4
Q

glycan-type receptor in innate immune system

A

TLC 4

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5
Q

Phagocytotic Leukocytes of Innate Immune system

name the 3

A

Neutrophils: In the bloodstream, detect infection with pattern recognition receptor, destroy small pathogens

Eosinophil-similar but target larger pathogens

Macrophages- differentiate from monocyte. Major function: Destroy human cells that have been compromised

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6
Q

innate immune cells initiate signaling increasing expression of many target genes by signaling pathways ________ and ______

A

G-protein coupled receptors like GPI modifications and JAK/SAT

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7
Q

what are the expressed proteins after the innate system has been triggered

A

(A) Chemokines- glycoproteins that attract other white cells (positive
feedback). The initiate signaling in target cells

(B) Complement pathways- is activated in three different manners at the
local infected site. Leads to recruitment of white cells, enhanced
phagocytosis by the process of opsonization and pathogen cell
membrane lysis.

(C) Adhesion molecules – many but forms a barrier and helps make cells
stick to the infection site.

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8
Q

chemokines

A

Chemokines-glycoproteins that attract other white cells (positive
feedback). The initiate signaling in target cells

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9
Q

Complement pathways-

A

Complement pathways- is activated in three different manners at the
local infected site. Leads to recruitment of white cells, enhanced
phagocytosis by the process of opsonization and pathogen cell
membrane lysis.

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10
Q

Adhesion molecules

A

Adhesion molecules – many but forms a barrier and helps make cells
stick to the infection site.

neutrophils burst open to form barrier

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11
Q

what an example of response with GPI anchors being cleaved in alpha Q

A

histamine release which bind to the H1 receptor

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11
Q

adaptive immune system
and cells

A

slow response

adaptive immune system termed lymphocytes and derive from
the “common lymphoid progenitor.” Two main types
(A) B-cell: produce antibodies and present pathogenic material to t-cells
(B) T-cell: directly kill infectious cells, activate other immune cells, regulate
immune response through cytokines.

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12
Q

what are GPI on GPCR and how does it work

A

in GPCR-aplha Q

they are glycolipids within the GPCR that anchor it to the cell membrame and if it get cleaved then initiates response

the glycolipids are localized within the cholesterol and sphingolipids

released from phospholipase C

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13
Q

H1 receptor drugs and their brand names (5)

and how do they work

A

second generation:
They bind to the H1 receptor but have a charge so they do not cross the barrier and do not make you sleepy

cetirizine (antihistamine) =trade name (zrytec)
levocetirizine= xyral
loratadine =claritin
desloratadine=clarinex
fexofenadine=allegra

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14
Q

hydroxylation

A

hydroxyl group to Proline and several
other amino acids

hydroxylation stabilizes collagen’s triple helical structure at every 3rd AA

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15
Q

lack of Lack of Vitamin C leads to ___

A

Scurvy: defective collagen formation leading to
subcutaneous hemorrhage, aching bones, joints,
and muscle in adults, rigid position and pain in
infants

Recommended daily amount: 75 mg (W), 90 mg
(M)

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16
Q

how does vitamin C help in the hydroxylation of collage

A

Collagen hydroxylation by prolyl-hydroxylase using
Vitamin C as a cofactor

17
Q

Lipidation and examples

A

or attachment of a lipid to a protein can be
used to anchor proteins to membranes

(1)Sequesteration of proteins to membranes

(2) S-palmitoylation

18
Q

what happens during S-palmitoylation

A

attaches a C16 palmitoyl group to the thiol of cysteine aa to give the protein a permanent ancher

but could be cleaved by thioesterases, therrefore can be used an an ON OFF switch for

19
Q

what happens to old proteins that are S-pamitoylated

A

acyl protein thioesterase can break the link of the cys and anchor and can be degraded in proteosome

20
Q

how does the ubiquitin proteosome system work?

A

the protein becomes inactivated when ubiquitin get attached to it.

ligases attach to ubiquitin ising isopeptide bond

then it is recognized by 26S proteosome —> degradation of protein and recycling of ubiquitin

21
Q

what happens with ubiquination under too much stress

A

more proteins being degraded and leads to cell death

protein folding disorders

22
Q

alzeheimers and huntigntons are diaseases due to not enough protein being degraded

A
23
Q

biologiocal signaling metabolic view

A

Outside information altering energy currency (ATP) usage and allocations in
a specific way.

Needs:
A) Specific for given situation
B) Amplifies (ie more ATP)
C) Integrates: on and off
D) timely: local and shuts off

24
Q

types of signaling

A

autocrine , immune ceels

signaling across cell junctions , neurons

paracrine , growth factors locally synchronize tissue

endocrine , hormones

25
Q

GPCR alpha S system (cAMP)- cAMP

endrocrine hormones

A

FLAT ChAMP CHuGG

FSH, LH, ACTH, TSH (FLAT)

CRH, hCG, ADH v2 receptor, MSH, PTH, (CHAMP)

calcitonin, histamine (h 2 receptor), Glucagon and GHRH(growth hormone releasing hormone) (CHuGG)

26
Q

GPCR alpha alpha Q system ( IP3)

A

GOAT HAG

GnRH, Oxytocyn, ADH v1, TRH (GOAT)

histamine (H1 receptor), Angiotensin II, gastrin (HAG)

27
Q

GPCR mechanism description until alpha subunit

A

in resting state, phosphate bound to protein
3- Gprotein subunits alpha beta and gamma with GDP bound

induced state:
ligand binds, phosphates come off, GTP displaces GDP

alpha unit disassociates ( follow S or Q system)

28
Q

the alpha S subunit of GPCR activate_____ and the ligand are_____ and ________

A

adenyl cyclase

Glucagon
epinephrine to regulate metabolic enzymes

29
Q

the alpha Q subunit of GPCR activates_____ and the ligands are _____ and ________

A

phospholipase Cβ

epinephrine (fear)
acetylcholine

30
Q

alpha i inhibits ____ and the ligands are____ and ____

A

adenylyl cyclase

serotonin(CB1) and cannabis(CB2)

brings you to relax state

31
Q

Mechanism after release of GαS

A

in resting state, phosphate bound to protein
3- Gprotein subunits alpha beta and gamma with GDP bound

induced state:
ligand binds, phosphates come off, GTP displaces GDP

alpha unit disassociates ( follow S

release of Gαs activates adenylyl cyclase (AC) —>cAMP —->many PKA —->target protein are phosporalated

32
Q

Mechanism after release of Gα Q

what are the 2 pathways

A

in resting state, phosphate bound to protein
3- Gprotein subunits alpha beta and gamma with GDP bound

induced state:
ligand binds, phosphates come off, GTP displaces GDP

alpha unit disassociates ( follow Q

  1. aplha Q binds to phospholipase C and PIP 2(cleaved into IP3 and DAG)
    —>IP3 + DAG —> PKC —–> target protein Phos
  2. aplha Q binds to phospholipase C and PIP 2
    —>IP3—>Ca 2+ release —-> calmodulin carries Ca2+
    —> ACTIVATES CaM kinases —>target protein
33
Q

how does Cholera infection occur

and how does cholera enter the body

and what Alpha system does it activate

A

caused by Vibrio cholerae

Voluminous rice water diarrhea
-Contaminated drinking water or aquatic species in same water
- Two major virulence factors:
(1) cholera toxin and (2) toxin-coregulated pilus
- Gram-negative bacteria that use flagella to bypass mucosal lining (intestines)

  1. Toxin-coregulated pilus binds to
    membrane ganglioside in
    intestines
  2. Cholera toxin frees Alpha protein
    leading to activate adenylyl
    cyclase
  3. Target proteins that activates:
    CFTR: Cl- and H2O transported out
    (back to intestine)
  4. Rice water diarrhea
34
Q

Wooping cough infection

virulance factors

vaccine against it

and what G system does it affect

A

Bordetella pertussis —> Pertussis toxin
-Airborne bacteria that infects the airways by breathing in
droplets
-Coughing and similar symptoms (whooping) symptoms
-Largely eliminated (DTaP) immunization for infants
- Two major virulence factors: (1) pertussis toxin (PTX) binds to cell receptor (2)adenylate cyclase toxin

  • Pertussis toxin activates adenylyl cyclase by “inhibiting the
    inhibitor” thus increasing cAMP
35
Q

how are the GPCR signals terminated

A

Phosphodiesterase –> cAMP to AMP

Phosphorylation: GPCR is forced to inactive state

beta Arrestin binds to receptor in place of trimeric G protein

36
Q

lipid hormones signaling

examples

A

intracellular receptors, cross cell membranes change transcription, translation and metabolism.

CAT PET TV

Cortisol, Aldosterone, testosterone

Progesterone, estrohen, T3 , T4, Vit D

37
Q

classes of steroid hormones

A

glucocorticoids (C21) –
deal with stress by increasing gluconeogenesis and down regulating immune action

mineralcorticoids (C21) –
maintain water and salt balance

progestogens (C21) – Sex hormone involved in menstrual cycle and reproduction

androgens (C19) – male sex hormones
Estrogens (C18) – female sex hormone

GAMPE

38
Q

Biochemistry of glucocorticoids

A

from adrenal cortex

Mechanism: dimerize and bind promoter to regulate genes as
enhancer (increase expression) or down (repression)

cortisol

39
Q

what are the effects of cortisol

A

increase activity of CNS, liver adipose, heart/pancrease
by increasing act of appetite, blood pressure, insulin resistance (cells dont take much gluc, sucked in by liver)
gluconeogesis

it also decreases activity of skletal muscle, fibroblast (Fb) immune system and bone

by deacreasing wound healing (fB), inflammation, bone formtion, muscle prefer protein

40
Q

dexamethdone

A

type of glucocorticoid
change mRNA in tissues

decreases inflammation by lowering IL-11

for covid infection