Tues 10/15

• Cell Communication Quiz is THURSDAY!

• One phosphate molecule, adenosine triphosphate (ATP), is the primary energy-transferring molecule in the cell

• ATP consists of an organic molecule called adenosine attached to a string of three phosphate groups

2

***REVIEW***ATP: An Important Source of Energy for

Cellular Processes

Between the receptor molecule that is activated and signal-transduction pathway that is to be activated, there may be a second messenger.

(Note-The hormone or signal that attaches the to the receptor site is called the first messenger.)

The most common secondary messengers include:

a. cyclic AMP

b. Calcium ions and inositol triphosphate.

cAMP: (second messenger)• Example: When epinephrine binds to its receptor

site, there is a corresponding increase in the amount of cAMP found in the cell.

• cAMP is a derivative of ATP. An enzyme (adenylyl cyclase) in the plasma membrane causes this reaction to occur.

• In this example, epinephrine activates a receptor site, that in turns activates the G-protein. The G protein now activates adenylyl cyclase which then makes cAMP from ATP.

• cAMP activates the epinephrine pathway which ultimately increases the amount of glucose in the blood stream.

Consider this pathway: epinephrine G-protein-linked receptor G protein adenylyl cyclase cAMP. Identify the second messenger.

A) cAMP

B) G protein

C) GTP

D) adenylyl cyclase

E) G-protein-linked receptor .

A

The second messenger is cAMP. The first messenger is epinephrine.

Calcium ions and Inositol Triphosphate (IP3):• Some signal molecules in animals induce responses by

increasing amount of Ca++ in the cytosol.

• Used in muscles, nerves, & certain hormones.

• Most of the time Ca++ in the cytosol is low because it is pumped into the E.R., mitochondria, & out of the cell.

• The release of Ca++ from E.R. reservoirs involves diacylglycerol (D.A.G.) and inositol triphosphate (IP3).

• D.A.G and IP3 are made by the cleavage of certain kind phospholipid in the plasma membrane.

• This is done when the G protein activates enzyme phospholipase C.

• Phospholipase C cleaves a plasma membrane in two to make D.A.G. and IP3.

• IP3 will then move to the E.R. and bind with a IP3-gated calcium channel to allow Ca++ to flow out.

• Ca++ will now combine with a protein called calmodulin.

• Once activated calmodulin will activate the biochemical pathway it is intended to activate. • Usually by

activating a kinase or phosphatase.

Protein phosphorylation is commonly involved with all of the following except

A) regulation of transcription by extracellular signal molecules.

B) enzyme activation.

C) activation of G-protein-linked receptors.

D) activation of receptor tyrosine kinases.

E) activation of protein kinase molecules.

C

The activation of the G-protein linked receptor are some sort of signal like a hormone, neurotransmitter, or ligand. It does not involve protein phosphorylation.

Types of cellular responses:

1. Ultimately activating an enzyme

2. Synthesis of a particular enzyme or protein

1. Activating an enzyme:

• Usually when cAMP, Ca++ or IP3 is activated it will interact with a specific enzyme to start the cascading effect.

• Different kinds of cells have different collections of proteins

• These different proteins allow cells to detect and respond to different signals

• Even the same signal can have different effects in cells with different proteins and pathways

• Pathway branching and “cross-talk” further help the cell coordinate incoming signals

• Blockage of a signal transduction pathway or a defective pathway can be deleterious, preventative, or prophylactic.

Signal transduction pathways benefit cells for all of the following reasons except

A) they help cells respond to signal molecules that are too large or too polar to cross the plasma membrane.

B) they enable different cells to respond appropriately to the same signal.

C) they help cells use up phosphate generated by ATP breakdown.

D) they can amplify a signal.

E) variations in the signal transduction pathways can enhance response specificity.

C

Signal transduction pathways benefit cells for all of the following reasons except cannot help cells use up phosphate generated by ATP breakdown.

Apoptosis• Cells that are infected, damaged, or have reached the end

of their functional life span often undergo “programmed cell death” = Apoptosis– “cell suicide”

• Cellular agents chop up DNA and organelles, cell shrinks & becomes lobed, cell parts are packaged in vesicles then engulfed & digested.

• Protects neighbor cells

from damage

Apoptosis Control• Triggered by signals that activate a cascade of

“suicide” proteins in cell destined to die.• Most of these proteins are in all cells but in

inactive form, regulation occurs at level of protein activity.

• Signal can originate from outside or inside the cell (nucleus=DNA damaged, ER=protein misfolding)

• Essential to development & maintenance• Involved in degenerative diseases (Parkinson’s,

Alzheimer’s, Cancer) & webbed fingers and toes.

To sum it all up….Epinephrine Example

• http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html

Why are these pathways so important for researchers and

doctors to understand???

Body cellstake up moreglucose.

Insulin

Beta cells ofpancreasrelease insulininto the blood.

Liver takesup glucose and stores itas glycogen.

Blood glucoselevel declines.

Blood glucoselevel rises.

Homeostasis:Blood glucose level(70–110 mg/100mL)

STIMULUS:Blood glucose level rises

(for instance, after eating acarbohydrate-rich meal).

Liver breaksdown glycogenand releasesglucose intothe blood.

Alpha cells of pancreasrelease glucagon intothe blood.

Glucagon

STIMULUS:Blood glucose level

falls (for instance, afterskipping a meal).

Figure 45.13

Out of Balance: Diabetes Mellitus

• Diabetes mellitus is perhaps the best-known endocrine disorder.

• It is caused by a deficiency of insulin or a decreased response to insulin in target tissues.

• It is marked by elevated blood glucose levels.

• Type 1 diabetes mellitus (insulin-dependent) is an autoimmune disorder in which the immune system destroys pancreatic beta cells.

• Type 2 diabetes mellitus (non-insulin-dependent) involves insulin deficiency or reduced response of target cells due to change in insulin receptors.

Out of Balance: Diabetes Mellitus

Action of Insulin

29

Ever heard of “a runner’s high”?

• Our body manufactures endorphins which are made by the pituitary gland and bind to the receptors in the brain that relieve pain and produce euphoria during times of stress, such as intense exercise.

• Opiates such as morphine and heroin are structured similarly, thus can bind with the receptors . These “bindings” are actually those electrostatic attractions we call IMFs.

30

The boxed regions are shaped similarly!

Natural endorphin

Morphine

Carbon

Hydrogen

Nitrogen

Sulfur

Oxygen

(a) Structures of endorphin and morphine

Pain killer!

• The brain receptors “bind” with either with similar results.

32

(b) Binding to endorphin receptors

Brain cell

MorphineNaturalendorphin

Endorphinreceptors