signal trans duct ion +tbl
TRANSCRIPT
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Signal
Transduction
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Signal transduction is thebiochemical process in whicha cell converts signals, thatare detected by cellreceptors, to cellular
response.
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Signal transduction is involved in:
- Cell-cell communication
- Cells response to environment
- Intracellular homeostatsis- internal
communication
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Generic Signalling Pathway
Signal
Receptor(sensor)
Transduction
Cascade
Targets
ResponseAltered
Metaboli
sm
MetabolicEnzyme
Gene RegulatorCytoskeletal Protein
AlteredGene
Expression
AlteredCell
Shape orMotilit
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Molecular Mechanisms of SignalTransduction
1- Specificity
2- Amplification
3- Desensitization
4- Integration
5- Sensitivity
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Specificity is promoted because
the receptors for a given signalor the intracellular targets of agiven signal pathway arepresent only in certain cell
types.
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For example, Thyrotropin- releasinghormone triggers responses in thecells of the anterior pituitary glands,
but not in hepatocytes, which lackreceptors for this hormone.
Epinephrine alters glycogenmetabolism in hepatocytes but not in
erythrocytes, although both celltypes have receptors for thehormone. However, hepatocytes havethe glycogen-metabolizing enzymes,but erythrocytes do not.
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e) Sensitivity:Three factors account for
the sensitivity of signaltransducers:
- The high affinity ofreceptors for signal molecules.
- Cooperativity in the ligand-
receptor interaction.- Amplification of the signal
by enzyme cascade.
S
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Signal Transduction
Receptor
Hormone Signal
G
Cyclase
Transducer
Effector Enzyme
Effector
Effect
G-protein
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Elements of a signal
transduction System Sender Signal
NondestructiveMedium Selective Receiver Transducer Amplifier Effector Res onse
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Signal = LIGAND
Ligand: A molecule that bindsto a specific site on anothermolecule, usually a protein, i.ereceptor
- What can be the Signal?External message to thecell
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Examples of signal molecules:
- Hormones
- Growth factors
- Cytokines.
- Neurotransmitters.
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General types of SignalTransduction
1- Gated ion channel:
Open and close in response tothe binding of chemical ligands orchanges in transmembranepotential.
2- G- protein Receptors.
3- Enzyme Receptors.
4- Steroid receptors.
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Types of receptor:
I- Cell-surface receptors
II- Internal or cytoplasmicreceptors
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Cell Surface Receptors
Transmembrane receptors:
A- G- protein coupled receptors.
B- Enzyme Receptors as Tyrosine kinasereceptors.
C- Integrins.
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G- proteinCoupled
receptors
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TyrosineKinase
Receptors
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Intracellularreceptors asSteroidReceptor
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Types ofReceptors
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Phosphorylation
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Phosphorylation
Conformational
ChangedephosphorylastionPhosphatase
P
Protein
OH
SerThr Tyr(His)
Active Inactive
Inactive Active
Glycogen phosphorylase b Glycogen phosphorylase a
Kinasephosphorylation
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Disturbed SignalTransduction
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Cystic Fibrosis
is an autosomal recessivediseasecommon amongCaucasiansby mutationsin the CFTR.
CFTR Regulates thetransport of chloride andother ions across the cell
membrane and hencenormal viscosity andfunction of mucosalsecretions.
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ySecond level
Third level Fourth level
Fifth level
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primarily affects the respiratory, digestiveand reproductive systems, as well as thesweat glands. The mucus secreted is verythick and blocks passageways in the lungsand digestive tracts with repeated infectionsand obstructions in both systems.
Foul-smelling bowel movements ,Mucus in stool ,Bulky bowel movements ,Steatorrhea - bulky soft foul-smelling stool ,Abdominal bloating ,Malnutrition ,
Delayed growth ,Weight loss,Pancreatic insufficiency , Enlarged liver ,Enlarged spleen
Salty sweat
http://www.wrongdiagnosis.com/sym/stool_odor.htmhttp://www.wrongdiagnosis.com/sym/mucus_in_stool.htmhttp://www.wrongdiagnosis.com/sym/bowel_movements.htmhttp://www.wrongdiagnosis.com/sym/steatorrhea.htmhttp://www.wrongdiagnosis.com/sym/abdominal_swelling.htmhttp://www.wrongdiagnosis.com/sym/malnutrition.htmhttp://www.wrongdiagnosis.com/sym/poor_growth.htmhttp://www.wrongdiagnosis.com/sym/weight_loss.htmhttp://www.wrongdiagnosis.com/sym/pancreas_symptoms.htmhttp://www.wrongdiagnosis.com/sym/enlarged_liver.htmhttp://www.wrongdiagnosis.com/sym/swollen_spleen.htmhttp://www.wrongdiagnosis.com/sym/sweat_symptoms.htmhttp://www.wrongdiagnosis.com/sym/sweat_symptoms.htmhttp://www.wrongdiagnosis.com/sym/swollen_spleen.htmhttp://www.wrongdiagnosis.com/sym/enlarged_liver.htmhttp://www.wrongdiagnosis.com/sym/pancreas_symptoms.htmhttp://www.wrongdiagnosis.com/sym/weight_loss.htmhttp://www.wrongdiagnosis.com/sym/poor_growth.htmhttp://www.wrongdiagnosis.com/sym/malnutrition.htmhttp://www.wrongdiagnosis.com/sym/abdominal_swelling.htmhttp://www.wrongdiagnosis.com/sym/steatorrhea.htmhttp://www.wrongdiagnosis.com/sym/bowel_movements.htmhttp://www.wrongdiagnosis.com/sym/mucus_in_stool.htmhttp://www.wrongdiagnosis.com/sym/stool_odor.htm -
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When cholera toxin is released fromthe bacteria in the infected intestine,it binds to the intestinal cells known
as enterocytes (epithelial cell inabove diagram) through theinteraction of the pentameric Bsubunit of the toxin with the GM1ganglioside receptor on the intestinalcell, triggering endocytosis of thetoxin.
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Next, the A/B cholera toxin must undergocleavage of the A1 domain from the A2domain in order for A1 to become an activeenzyme. Once inside the enterocyte, the
enzymatic A1 fragment of the toxin Asubunit enters the cytosol, where it activatesthe G protein Gsa through an ADP-ribosylation reaction that acts to lock the Gprotein in its GTP-bound form, therebycontinually stimulating adenylate cyclase to
produce cAMP.
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The high cAMP levels activate the cysticfibrosis transmembrane conductanceregulator (CFTR), causing a dramatic effluxof ions and water from infected enterocytes,leading to watery diarrhoea.
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w Cholera toxin catalyzes covalentmodification ofGs .
+ .
.
.
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F ili l H h l t l i
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Familial Hypercholestrolemia(LDL receptor deficiency)
Familial Hypercholestrolemia is anautosomal dominant single gene disease
characterized by elevated cholesterol levelsand increased risk for coronary arterydisease due to deposition of Cholesterol inthe vessel wall.
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Presenting features:
Subcutaneous yellowish nodules seen onextensor aspects on elbows and knees
(xanthomas)Deposition of lipids in eyelids(xanthelasmas)
Increased risk for cardiovascular andcerebrovascular disorders due to narrowingof the blood vessels and ischemia.
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Pathophysiology :
FH is a disorder of absent or grossly malfunctioninglow-density lipoprotein (LDL) receptors. T
he circulating cholesterol bound to LDL attaches the
LDLR on the cell membrane of hepatocytes. Onceinternalized by endocytosis, it separates LDLR which isrecycled back to cell membrane. Inside lysosomes,cholesterol dissociates from its carrier complex proteinthen serves in the synthesis of steroid hormones, bileacids and as a constituent in cell membranes. Excesscholesterol is stored as esters.
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Thank you & good
luck