BioChem CH 13/14 E2

what do signal transduction cascades have in common

1.release of primary messenger
2.reception of primary messenger by a receptor (integral membrane protein)
3.relay of the detection of the primary messenger to the cell interior
4.activation of effector molecules by the second messenger
5.termination of the signal cascade

what are the 3 major classes of membrane receptors

1.7-transmembrane-helix receptors associated with heterotrimeric G-proteins
2.dimeric membrane receptors that recruit protein kinases
3.dimeric protein receptors that are protein kinases

what do 7TM receptors mediate

-a host of biological functions by responding to a variety of signal molecules (ligands), including hormones, tastants and photons

how does ligand binding to 7TM receptors lead to the activation of G proteins

• A ligand like epinephrine binds to a 7-transmembrane (7TM) receptor, such as the β-adrenergic receptor.

• This causes a change in the receptor’s shape, which activates a heterotrimeric G protein inside the cell.

• The Gα subunit of the G protein releases GDP and binds GTP instead.

• The GTP-bound α subunit then separates from the βγ dimer and goes on to activate downstream signaling pathways.

activation of what leads to the synthesis of the second messenger

-cyclase (cAMP)

how does cyclic AMP stimulate the phosphorylation of many target proteins

-by activating protein kinase A
-kinase A has 2 pairs of subunits: 2 catalytic and 2 regulatory
-binding of cAMP by regulatory subunits dissociates these subunits from the complex, resulting in activation of 2 C subunits
-activated C continue the epinphrine signal transduction pathway by phosphorylating protein targets that alter physiological functions of the cell

what is Cushings syndrome

-excess cortisol secretion is the cause
-muscle weakness, thin and easily bruised skin
-sometimes caused by constituitively active protein kinase A. Catalytic subunit does not bind the regulatory subunit and is never inhibit

how is the epinphrine-imitated pathway shit down

• Gα breaks down GTP → GDP, turning itself off.

• Phosphodiesterase turns cAMP → AMP, stopping PKA activation.

• Epinephrine detaches when levels drop, inactivating the receptor.
  
  (TextBook) -Galpha has inherent GTPase activitiy that cleaves the bound GTP to GDP
  -cyclic AMP phosphodiesterase converts cAMP to AMP which does not activate protein kinase A
  -epinephine-beta-adrenergic receptor interaction is reversible. (once e falls, receptor will no longer be active)

list the means by which the beta-adrenergic pathway is terminated

-cyclic AMP → AMP
-primary messenger dissociates off
-hydrolysis of GTP → GDP

what is protein Ras

-part of the small G proteins (monomeric)
-is active when bound to GTP and inactive when bound to GDP; controls signal duration

how does insulin regulate metabolism

Insulin is released when glucose is high, binds to its receptor (a tyrosine kinase), and triggers a cascade that increases glucose uptake and storage.

-is secreted when the blood is rich in glucose
-insulin receptor is a receptor tyrosine kinase
-insulin receptor exists as a dimer even in absence of insulin

how does the activated insulin-receptor kinase initiate a kinase cascade

• Insulin binds to its receptor, causing it to change shape and activate its kinase domains.

• The receptor phosphorylates IRS proteins, which act as messengers inside the cell.

• PI3K binds to IRS and converts PIP2 into PIP3 (a signaling lipid).

• PIP3 activates PDK1, which then activates the Akt kinase.

• Akt increases glucose uptake by moving GLUT4 transporters to the cell surface and also helps store glucose as glycogen.

What role does calmodulin play in calcium (Ca²⁺) signaling, and what happens when it binds calcium?

• Calcium (Ca²⁺) is a major second messenger in cell signaling.

• Calmodulin is a Ca²⁺-binding protein that senses calcium levels.

• It has 4 binding sites (EF hands) and becomes active when Ca²⁺ binds.

• The Ca²⁺-calmodulin complex can activate proteins like:

  • Ca²⁺ pumps (to remove Ca²⁺ from the cell)

  • CaM kinase, which helps regulate other enzymes

• Ca²⁺ also plays a role in the phosphoinositide signaling pathway.

How are pancreatic enzymes activated in the small intestine?

• Pancreatic enzymes are made as inactive proenzymes (zymogens) stored in granules near the cell membrane.

• When triggered, these granules release zymogens into the intestine.

• Zymogens become active enzymes when a part is cut off (proteolytic cleavage).

• Enteropeptidase (on intestinal cells) activates trypsinogen by turning it into trypsin.

  • Trypsin then activates the other pancreatic enzymes.

how does the protein digestion begin in the stomach

-the highly acidic environment of the stomach denatures proteins, making them more susceptible to digestion by proteolytic enzymes such as the stomach enzyme pepsin

what does movement of food from the stomach to the intestine stimulate

-secretion of 2 key hormones by cells of the small intestine
-secretin causes the release of sodium bicarbonate (a base) which neutralizes stomach acid
-cholecystokinin (CCK) stimulates the release of digestive enzymes from the pancreas as well as secretion of bile salts from the gallbladder

how are proteins digested

-in small fragments called oligopeptides (4-20 a.a)
-peptidases on the surface of intestinal cells cleave the oligopeptides into amino acids

what is celiac disease

-an intestinal inflammatory disorder that results because susceptible individulas are genetically disposed to mount an inflammatory response to gluten-derived peptides

Which enzymes digest starch and disaccharides, and how are glucose, galactose, and fructose absorbed in the intestine?

• Starch is our main carbohydrate source.

• α-Amylase starts digestion by cutting α-1,4 bonds (not α-1,6).

• Other enzymes like α-glucosidase and α-dextrinase finish breaking down starch.

• Sucrose and lactose are broken down by sucrase and lactase, respectively.

• Glucose and galactose enter intestinal cells via the sodium-glucose linked transporter.

• Fructose enters via the GLUT5 transporter.

what do lipases do

-convert the triacylglycerols into 2 fatty acids and monoacylglycerol
-digestion products are carried as micelles to the intestinal epithelium cells for absorption