Chapter 23: Signal Transduction Mechanisms

These are part of the body seen in the digestive system that is controlled by cell signaling pathways.

taste buds

This is secreted by the adrenal gland. Responsible for Fight or flight situation

Adrenaline/epinephrine

For epinephrine = adrenergic/adreno receptors. Epinephrine accepts the ligand in this pathway

Epinephrine Transduction Pathway

These are the primary messengers of the Epinephrine Transduction Pathway that resulted to the production of secondary messenger

Epinephrine

Body will respond with increased heartbeat and glycogen breakdown because of this.

Epinephrine

This is considered the secondary messengers in ETP. Activates protein kinases

cAMP

Transport movement of phosphate molecules from molecule to molecule. Power cellular reactions

Kinases

What can be seen in this photo?

Ligand-receptor binding

TRUE OR FALSE:
In the most cases the binding of a receptor and ligand resembles the binding of an enzyme and its substrate

True

The receptor specific for a certain ligand is called the

cognate receptor

A receptor bound to its ligand is said to be

occupied

Facilitate increase the binding between ligand and receptor

Co-receptors

Can you allow cell signaling to continue happening? Needs regulation or not?

Signals regulate

TRUE OR FALSE:
Cells are geared to sense fixed concentrations rather than ligand concentration changes

False

TRUE OR FALSE:
When receptors are occupied for prolonged periods, the cell adapts and longer respond to the ligand

True

When receptors are occupied for prolonged periods, the cell adapts and longer respond to the ligand. These changes are called?

receptor down-regulations

A receptor-down regulation that is accomplish to decrease response

down-regulate

A receptor-down regulation that is accomplish to increase response

up-regulated

Cells reduce the density of receptors on their cell surfaces via

receptor-mediated endocytosis

There are no more receptors, nothing to accept the ligand, no more signals. Reducing the effect of the receptors by eliminating or lessening the receptors. Small portions of the plasma membrane containing the receptors are internalize

Endocytosis

Allows cells to internalize receptors and extracellular molecules, bringing them into the cell via protein-coated vesicles

Clathrin-Dependent endocytosis

In Clathrin-Dependent endocytosis, this allows cells to internalize receptors and extracellular molecules, bringing them into the cell via?

protein-coated vesicles

Allows the selective transfer of macromolecules. Concentrates the receptor molecules and the internalized receptors are transported in the vesicles. Can down regulate via activating the clathrin.

Clathrin-Dependent endocytosis

TRUE OR FALSE:
Clathrin-Dependent endocytosis is important in the removal of the receptors from the plasma membrane

True

Cells can adapt to signals by __________, alterations to the receptor that lower its affinity for the ligand

desensitization

Refers to the decreased responsiveness. Happens upon chronic/repeated exposure to ligand or agonists

desensitization

Desensitization is like _______ feedback mechanisms that shuts off the receptor or making it less receptive to a particular ligand

negative

TRUE OR FALSE:
In desensitization, ligand activation triggers a feedback circuit that shuts off the receptors or removes it from the cell surface

False

TRUE OR FALSE:
It is possible to make synthetic ligands that bind even more tightly or selectively than the real ligand

True

Drugs that activate the same receptor they are bound to. Examples are Heroine and Morphine

Agonists

Bind receptors without triggering a change, and prevent the naturally occurring messenger from activating the receptor

Antagonists

Ligands that sort of triggering a change and prevent the activation of the receptor, the end result of the antagonist is?

No effect

TRUE OR FALSE:
Cells can be exposed to a multitude of signals at certain moments

False

TRUE OR FALSE:

A single receptor can activate multiple pathways, or multiple pathways can converge into the same molecules

True

Sometimes activated components from one pathway affect components of another pathway, this is called

signaling crosstalk

TRUE OR FALSE:
Signaling is more of a network of linear sequence of events than a biochemical pathways

False

TRUE OR FALSE:
Components from one pathway will have an influence on the components or molecules in any other pathway

True

TRUE OR FALSE:
Very small quantities of ligand are often sufficient to elicit a response from a target cell

True

TRUE OR FALSE:
At each step in the resulting cascade of events, a signaling intermediate stimulates the production of many molecules needed for the next step

True

The multiplication of the effect of the signal is called

signal amplification

THIS IS AN EXAMPLE PROCESS OF SIGNAL AMPLIFICATION, ARRANGE THE FOLLOWING IN THE CORRECT ORDER

A. Begin with 1 molecule -> activate G protein -> Activation of 100 molecules - > so on and so forth

B. Adrenal gland will produce epinephrine in response to stressful situation

C. Moving one step to another will lead to producing 10^2 molecules

B, A, C

In here, we want to produce more glucose for energy

Fight or flight

TRUE OR FALSE:

Small quantities of ligand is not enough to elicit a major response resulting to production of many molecules

False

Controls the regulation of blood glucose levels via Negative Feedback System

Insulin and Glucagon

Causes the blood glucose level to increase. Long chains of repeating glucose units. During digestion, this is broken to glucose and absorbed by the bloodstream

Carbohydrates

Increase in blood glucose level causes the pancreas to secrete

insulin

Pancreas is a gland that secretes hormones which act on specific target organs. What target organ is stimulated to convert glucose to glycogen

liver

Long multibranched of glucose monomers stored in livers and muscle cells

Glycogen

Insulin also causes the body cells to uptake or take in glucose decreasing the blood glucose level into the optimal state. The faulty state is?

Diabetes

Secreted when blood glucose level drops (when you’re hungry)

Glucagon

The target organ of glucagon where it increases the blood glucose level to its optimal state

liver

Taste receptors responsible for sweet taste

T1r2 and T1r3

Taste receptors responsible for savory and umami tastes

T1r1 and T1r3

TRUE OR FALSE:
Receptors can be classified into several basic categories

True

Categories of Receptors

Ligand-gated channels, GPCRs

A huge family of receptors. Facilitates cell signaling and different types of cellular responses. Have a similar structure but quite different amino acid sequence

G protein-coupled receptor (GPCR)

Guanine-nucleotide Binding protein

G protein

Causes a change in receptor conformation that activates a particular G protein

Ligand binding

Each GPCR has _________________________ connected by alternating cytosolic or extracellular loops. Crosses the phospholipid bilayer. There are external and internal loops

seven transmembrane alpha-helices

Terminus that is is exposed to the extracellular fluid

N terminus

Terminus that is residing in the cytosolic region (within the cell/internally) and interacts with G proteins.

C terminus

TRUE OR FALSE:
A ligand binds to the extracellular portion of the receptor, causing an intracellular portion of the receptor (also cytosolic loops) to bind and activate a G protein

True

This is considered the first step in GPCR

Ligand Binding

This is considered the second step in GPCR. This activates a particular G protein coupled to the certain receptor

change in conformation/shape

The loop itself creates the messenger-binding site for a particular messenger or chemical or ligand

Messenger binding site

Reacts with the G protein

Cytosolic loop

Activation will activate Adenylyl cyclase

G protein

When activated, will produce cyclic AMP from ATP

Adenylyl cyclase

Will become the second messenger. Activates Protein Kinase A

cAMP

G protein-linked receptors examples:

olfactory, taste, beta-adrenergic, hormone, opiod receptors

Even pain and itch as well as allergic dermatitis are explained by the

GPCR

Carried out by the G-protein coupled receptor kinases (GRKs). Act on activated receptors

Phosphorylation

Phosphorylation is carried out by the

G-protein coupled receptor kinases (GRKs)

Binds phosphorylated Betaadrenergic receptors and inhibits them. Proteins that are versatile, multifunctional adapter proteins that are best known for their ability to desensitize GPCRs (negative regulators) and to regulate cellular functions

Beta-arrestin

TRUE OR FALSE:
Upon GPCR activation *when phosphorylated, Beta-arrestins bind to antagonist-occupied receptors, completely inhibiting ability to associate with G proteins

False

Activated by G Protein-mediated signaling. In turn, this can phosphorylate other amino acids on the receptor and inhibit it

Protein Kinase A

are stimulators of signal transduction

Gs

are inhibitors of signal transduction

Gi

G proteins is considered?

Heterotrimeric

What are the three subunits of G proteins?

G alpha, G beta, G gamma

They mediate signal transduction coupled to the (or through the) GPCR and act like molecular switches

G proteins

TRUE OR FALSE:

G protein, like molecular switches whose “on” and “off” states depend on whether they are bound to Guanosine Triphosphate (GTP) or Guanosine Diphosphate (GDP)

True

Largest subunits. When in inactive resting stage, it is bound to GDP. When it starts binding to GTP, it is activated

Ga

When Ga is bound to GDP it is?

resting/inactive

When Ga is bound to GTP it is?

active

This Binds to GDP and GTP

GBy

TRUE OR FALSE:
When Ga binds to GTP, it detaches from GBy subunits which are permanently bound together

True

In the step 1 of G protein activation, when a ligand (messenger) binds to a ______________ the resulting change in receptor conformation causes a G protein to associate with it and release its GDP

G protein-coupled receptor

In the step 2 of G protein activation, the Ga then binds a new GTP molecule and detaches from the complex. Signal pathways govern the?

alpha subunits

TRUE OR FALSE:
In the 3rd step of G protein activation, either the Ga or the GBy initiates signal transduction depending on the G protein

True

ARRANGE THE FOLLOWING BASED ON G PROTEIN INITIAL ACTIVATION:

A. Alpha unit will separate to the beta and gamma subunits

B. GTP is binded and alpha subunits detaches from the protein complex

C. GDP is released

C, B, A

TRUE OR FALSE:
In G protein inactivation, G proteins remain active as long as the Ga subunits is bound to GTP and separate from the GBy subunit

True

TRUE OR FALSE:

In G protein inactivation, Once the Ga subunit has hydrolyzed GDP to GTP, it reassociates with GBy

False

The most important G protein function is

formation of second messenger

Production of cAMP is formed from?

ATP

Activation of adenylyl cyclase will promote the conversion of ATP to

cAMP

Activation of Protein Kinase A inhibits?

Glycogen synthesis

The entire sequence, from signal reception to cellular response is referred to as

signal transduction pathway

In the fight or flight response, the adrenal glands release the hormone __________, a signaling molecule within the body

epinephrine

Certain cells (such as _______ cells) can detect the signal, after which they process the signal and respond to it

liver