Exam 3 (HW, Reading Quiz, and Textbook) Chapter 12 - 17

Suppose that each β-adrenergic receptor bound to epinephrine converts 100 molecules of the Gα subunit to the GTP-bound form, Gαs. If each molecule of activated adenylate cyclase produces 1000 molecules of cAMP per second, how many molecules of cAMP are produced in 10 seconds after the formation of a single complex between epinephrine and the β-adrenergic receptor? Assume the pathway is fully responsive.

100 G𝛼 × 1000 cAMP × 10 sec = 1×106 molecules of cAMP

About how many grams per day of protein is sloughed off the cells of the intestine through the wear and tear of digestion?

50-100

Correct statements about calmodulin

A calcium ion is bound in the loop of an EF hand. Binding of Ca2+ activates calmodulin. Each calcium-binding domain in calmodulin is formed a helix-loop-helix motif.

Digestion process of a complex carbohydrate

A person takes a bite and begins to chew the complex carbohydrate into smaller pieces The enzyme amylase, which is present in salvia, breaks polysaccharide chains into disaccharides Amylase is deactivated by the low pH in the stomach Other enzymes in the small intestine further break the polysaccharide into monosaccharides Monosaccharides are absorbed through the intestinal wall

Statements that describe signal transduction pathways

A receptor changes conformation upon binding, transmitting a signal across the cell membrane. A ligand, such as a hormone, binds to a specific cell surface receptor on a target cell. Signal transduction cascades, often involving protein kinases, amplify a signal intracellularly. A second messenger may carry a signal from the cell membrane to an organelle. Phosphatases remove phosphoryl groups from polypeptides, regulating a cell's response. A receptor may pass on a signal by interacting with another protein or by acting as an enzyme.

Stimulate secretin release

Acidic chyme entering the duodenum

Heterotrimeric G proteins

Activated by 7TM receptors Active form dissociates to Gα and Gβγ Inactive form binds GDP Active form binds GTP

Small G proteins

Activated by dimerized growth factor receptors Monomeric in both active and inactive forms Inactive form binds GDP Active form binds GTP

Which statements are true of P‑type ATPases?

All P‑type ATPases convert between different conformational states to transport ions or molecules. All P‑type ATPases use a similar mechanism of action involving a phosphorylated intermediate. Their widespread presence in living organisms suggests an early evolutionary origin for P‑type ATPases.

Membrane‑spanning β strands

Amino acid sequence pattern: nonpolar R group, polar R group (repeats)

P-type ATPase transporters

An aspartate residue in the membrane pump is phosphorylated The gastric H+-K+ ATPase is an example Catalytic cycle begins with substrate bound but ATP not bound ATP-dependent Substrate binds before ATP

Ligand-gated ion channels

An example is the acetylcholine receptor Change conformation in response to a signal molecule binding Is a form of passive transport May participate in an action potential

Peripheral membrane proteins

Attach at the cell membrane surface

Why does calmodulin bound with calcium interact with target proteins, whereas free calmodulin does not?

Calcium binding results in a conformational change in calmodulin, producing a structure that can bind to target proteins.

Integral membrane proteins

Can extend through the cell membrane Can move laterally (sideways) in the hydrophobic part of the membrane Acts as tunnels through the cell membrane

Peripheral membrane protein

Can usually be released from membrane by concentrated salt solutions Often tethered to membrane via a membrane-embedded protein

Kinases

Catalyze phosphorylation reactions May use ATP as a phosphoryl group donor PKA (protein kinase A) is an example Regulate the activity of other proteins

Voltage-gated ion channels

Change conformation in response to changing membrane potential Is a form of passive transport May participate in an action potential

Multidrug resistance can make it difficult to treat cancer successfully with chemotherapy. What causes multidrug resistance in cancer cells?

Chemotherapy drugs and other toxins are actively pumped out of cancer cells by transmembrane proteins

On the graph, the curve labeled No Cholesterol shows the fluidity of the fatty acids of a phospholipid bilayer as a function of temperature. The curve labeled + Cholesterol shows the fluidity in the presence of cholesterol. The transition temperature, Tm, is the temperature at which membranes transition between a rigid state and a more fluid state. What is the effect of cholesterol in the cell membrane? Why might this effect be biologically important?

Cholesterol regulates membrane fluidity over a wide temperature range. Membrane protein function depends on appropriate membrane fluidity.

Membrane-spanning α helix

Composed of about 20 hydrophobic residues

Steps of the activation of PKA starting after the adenylyl cyclase reaction

Cytosolic cAMP concentration increases. Two cAMP molecules bind to each PKA regulatory subunit. The regulatory subunits move out of the active sites of the catalytic subunits, and the R2C2 complex dissociates. The free catalytic subunits interact with proteins to phosphorylate Ser or Thr residues.

Simple diffusion

Directly through membrane O2 Lipophilic molecules Steroid hormones CO2

You prepare a cell line that overexpresses a mutant form of epidermal growth factor receptor, or EGFR, in which the entire intracellular region of the receptor has been deleted. Predict the effect of overexpression of this construct on epidermal growth factor (EGF) signaling in this cell line. What will be the effect of the overexpression of this truncated receptor?

EGFR will dimerize but will not cross-phosphorylate, inhibiting normal cell growth.

The proteolytic enzyme trypsin is produced in the pancreas as the zymogen trypsinogen. Trypsinogen is cleaved to yield the active form. Trypsin, in turn, activates other pancreatic zymogens. Select every enzyme that is used in the activation of trypsinogen. Select every pancreatic zymogen that is directly activated by trypsin.

Enteropeptidase (enterokinase) Proelastase Chymotrypsinogen Prolipase Procarboxypeptidase

Hydrolysis of ______ bonds in triacylglycerols yields products including _______.

Ester Fatty acids

Which step occurs immediately after epinephrine binds to the β‑adrenergic receptor?

GTP displaces GDP in Gαs.

Glucagon is a hormone that is released when the level of glucose in the blood is low. Glucagon uses a G protein signaling pathway to promote glycogenolysis. Put the steps of the signal transduction pathway in order from the releasing of glucagon into the blood to the promotion of glycogenolysis.

Glucagon is released into blood. Glucagon binds extracellulary to G protein-coupled receptor. G protein releases GDP and binds GTP. Activated G proteins activates adenylate (adenylyl) cyclase. Adenylate cyclase converts ATP to cAMP. Cyclic AMP activates protein kinase A. Phosphorylase kinase phosphorylates glycogen phosphorylase. Glycogenolysis is promoted.

Hydrolysis of the ______ bonds of carbohydrates yields _______.

Glycosidic Monosaccharides

Which of the subunits, when activated, associates with adenylyl cyclase (adenylate cyclase) and enables it to assume a more catalytically active conformation?

Gα

Arrange the substances in order of decreasing permeability through a lipid bilayer membrane.

High permeability Indole Glycerol Glucose Cl- Low permeability

Symporters, such as sodium-glucose linked transporter (SGLT), transport both Na+ and glucose. Na+-K+ ATPase uses ATP to transport Na+ ions out of the cell. What is the result of SGLT inhibition?

Inhibition of the Na+-K+ ATPase

Steps of the insulin signal pathway

Insulin is secreted Binding of insulin to the 𝛼 subunit of the insulin receptor Activation of insulin receptor tyrosine kinase Phosphorylation of IRS proteins Phosphorylation of phosphoinositide 3-kinase (PI-3K) Conversion of PIP2 to PIP3 Activation of PIP3-dependent protein kinase B (PDK1) Activation of Akt GLUT4 receptors transported to cell membrane Glucose enters cell

Glucose is mobilized for ATP generation in muscle in response to epinephrine, which activates Gαs. Cyclic AMP phosphodiesterase is an enzyme that converts cyclic AMP (cAMP) into AMP. How would an inhibitor of cAMP phosphodiesterase affect glucose mobilization in muscle?

It would maintain high cAMP levels and elevate glucose mobilization.

Statements that accurately describe receptor tyrosine kinases (RTKs)

Ligand binding is required for autophosphorylation (cross-phosphorylation). Some RTKs are dimeric in the presence of a ligand. A ligand binds to the extracellular domain. The structure includes a transmembrane helix

The process of digestion in the stomach is carried out in two main ways. One way involves the environment that exists in the stomach. What environmental condition within the stomach promotes digestion?

Low pH

Carbohydrate digestion begins in the _____ with the enzyme _________.

Mouth Salivary amylase

Active transport

Movement across a membrane Movement assisted by proteins Requires energy Sodium ion transport out of cell

Facilitated diffusion

Movement to area of lower concentration Movement across a membrane Movement assisted by protein Glucose transport into muscle cell Via channel Na+ Polar molecules Lactose Glucose

Saliva is an aqueous solution of these ions

Na+, K+, and HCO3-

flowchart showing the cleavage of a membrane lipid Which compounds can be considered second messengers?

PIP2 is hydrolyzed by PLC to produce DAG and IP3 IP3 diffuses to the ER where it causes the release of Ca2+ DAG and Ca2+ activate PKC which phosphorylates Ser or Thr Ca2+ IP3 DAG

Target of secretin

Pancreas

True statements about protein digestion and hydrolysis

Pepsin causes the hydrolysis of some of the peptide bonds in proteins. In the small intestine, carboxypeptidase attacks peptide bonds.

People with achlorhydria suffer from an abnormal composition of gastric fluid. Why does a person who has achlorhydria have difficulty digesting proteins?

Pepsinogen cannot be converted to pepsin in the absence of hydrochloric acid

Hydrolysis of the _____ bonds of proteins produces _________.

Peptide Amino acids

There is a larger number of a hydrophilic molecules on the outside of a cell than on the inside. Identify the conditions that could equalize the intracellular and extracellular concentrations of this molecule. Which condition would be the most metabolically‑efficient way for a cell to equalize the intracellular and extracellular concentrations of this molecule?

Placing channel proteins in the membrane Placing intracellularly-directed and extracellularly-directed pumps in the membrane Placing channel proteins in the membrane

Which molecules bind to receptors that have intracellular tyrosine kinase domains?

Platelet-derived growth factor Insulin

True statements about the transport system

Pumps Na+ ions out of the cell Pumps K+ into the cell Exchanges 3 Na+ ions for 2 K+ ions Creates a membrane potential that is negative on the inside

RTK

Receptor activation causes phosphorylation of its cytosolic subunits An example is the insulin receptor Autophosphorylation of receptor can initiate signal Ligand binding induces conformational change in receptor

Phosphatases

Remove phosphoryl groups from proteins Turn off signal pathways triggered by kinases Regulate the activity of other proteins

Calculate the distance olive oil (a lipid) could move in a membrane in 13 seconds13 seconds assuming the diffusion coefficient is 1 𝜇m2/s1 μ⁢m2/s . Use the equation S=(4Dt)1/2S=(4Dt)^1/2 where S is distance traveled, t is time, and D is the diffusion coefficient.

S = (4Dt)^1/2 S = (4 x 1 x 13)^1/2 S = 7.2 𝜇m

Produce secretin

S cells of duodenum

Fundamental properties of all ion channels

Selectivity Rapid transport

Increased levels of cholecystokinin (CCK) lead to a feeling of satiety. CCK is a family of peptide hormones released from the

Small intestine

Trypsin inhibitor is a pancreatic polypeptide that binds trypsin with very high affinity. Trypsin inhibitor deficiency can cause pancreatitis (inflammation of the pancreas). In normal digestion, trypsin activates several zymogens or proenzymes in which organ? What are the effects of trypsin inhibitor?

Small intestine Trypsin inhibitor blocks the proteolytic activity of trypsin Trypsin inhibitor prevents zymogen activation in the pancreatic ducts

Fat digestion begins in the _________ with the enzyme _________.

Small intestine Pancreatic lipase

Nucleic acid digestion begins in the ________ with the enzyme __________.

Small intestine Pancreatic nuclease

Starch is a common carbohydrate that is found in vegetables and grains. Which statement describes the structure of starch? Which of the statements is true regarding the digestion of starch and cellulose by humans?

Starch is a polymer of glucose Humans lack the enzymes required to hydrolyze the beta linkages in cellulose

Effect of secretin

Stimulates secretion of bicarbonate rich fluid

Biochemical roles of cholecystokinin (CCK)

Stimulates the secretion of bile salts by the gallbladder Stimulates the secretion of digestive enzymes by the pancreas

Protein digestion begins in the _______ with the enzyme _______.

Stomach Pepsin

GPCR

Structure contains seven transmembrane helices Activate heterotrimeric G proteins directly An example is the epinephrine receptor Phosphorylation of receptor can terminate signal or desensitize receptor Ligand binding induces conformational change in receptor

Secondary transporters, or cotransporters, can be divided into symporters and antiporters. What distinguishes symporters from antiporters?

Symporters use the energy from one molecule moving down its concentration gradient to drive the movement of a second molecule in the same direction against its concentration gradient. Conversely, antiporters drive the movement of molecules in opposite directions.

Which transport systems utilize a chemical reaction for the energy source?

The Ca2+ ATPase of the sarcoplasmic reticulum The Na+/K+ ATPase of plasma membranes

After a period of time, Gα ceases to stimulate adenylate cyclase. What is the consequence of Gα ceasing to stimulate adenylate cyclase?

The G protein's GTPase activity removes a phosphate, allowing Gα to diffuse back to Gβγ.

Primary active transporter

The Na+/K+ ATPase of plasma membranes The Ca2+ ATPase of the sarcoplasmic reticulum

Secondary active transporter

The amino acid - Na+ transporter of kidney cells The glucose - Na+ transporter of intestinal epithelial cells

Which of the outcomes could potentially result if a mutation in the gene encoding the Gα subunit eliminates its GTPase activity?

The concentration of cAMP in the cell would be continuously elevated. Gα would be activated for an extended period. The signaling pathway could be activated for an extended period, possibly resulting in undesirable cell proliferation.

Passive transporter

The glucose transporter of erythrocytes

ABC transporters

The multidrug resistance protein (P-glycoprotein) is an example Two ATP-binding domains Catalytic cycle begins with neither substrate nor ATP bound, with the transporter able to convert between closed and open forms ATP-dependent Substrate binds before ATP

Why are membrane receptor proteins often used to transfer information from the cell's environment to its interior?

The signal molecule is too large or too polar to pass through the cell membrane

Which three of the statements are true?

The tendency of water to minimize its contact with nonpolar substances is called the hydrophobic effect. Hydrophobic molecules do not readily dissolve in water in part because water molecules involved in hydration cannot participate in normal hydrogen bonding with one another. Amphipathic (amphiphilic) lipids are the structural basis of biological bilayer membranes.

Tumor suppressor genes

These genes code for proteins that normally prevent uncontrolled cell division. Mutations that decrease activity of these genes may lead to cancer. Some products of these genes normally function in repairing damaged DNA.

Proto-oncogenes

These genes code for proteins that normally promote cell division. Mutations that increase activity of these genes may lead to cancer.

Consider a uniport system where a carrier protein transports an uncharged substance A across a cell membrane. Suppose that at a certain ratio of [A]inside to [A]outside , the Δ⁢G for the transport of substance A from outside the cell to the inside, Aoutside→Ainside , is 13.9 kJ/mol at 25°C. What is the ratio of the concentration of substance A inside the cell to the concentration outside? Choose the true statement about the transport of A under the conditions described.

[A]inside/[A]outside= e^(Δ⁢G/RT) [A]inside/[A]outside= e^(13.9 x 1000)/(8.315 x (25 + 273)) [A]inside/[A]outside= 273 Movement of Ainside to Aoutside will be spontaneous

What is a zymogen?

a protein that is the inactive form of an enzyme

What factor enables Ca2+ to regulate many biochemical processes?

binding to calmodulin

Molecules that are used as second messengers in signal transduction pathways

cAMP IP3 Calcium ions

How does cAMP regulate protein kinase A?

cAMP binds to the regulatory subunits of protein kinase A, causing a conformational change that releases the catalytic subunits to carry out phosphorylation.

Uniport

carries only one solute at a time

The hydrolysis of phosphatidylinositol bisphosphate (PIP2) by phospholipase C generates what two secondary messengers?

diacylglycerol and inositol 1,4,5‑triphosphate

Bile salts, which aid in lipid adsorption, are synthesized from cholesterol in the liver and released into the small intestine from the

gallbladder

Hydrolysis of maltose

glucose

Hydrolysis of sucrose

glucose and fructose

Hydrolysis of lactose

glucose and galactose

Structural features common to all membrane-bound receptors

intracellular domain undergoes structural changes upon extracellular ligand binding. Signal molecule binding site on the extracellular domain

The GTPase activity of G proteins is important because

it provides a method whereby the initial signal can be terminated

Chylomicrons are

lipoprotein transport particles

Lipid-anchored membrane protein

often contains residues with covalently attached fatty acyl groups

Antiport

opposite direction

The Na+-K+ pump is an active transport system that

pumps Na+ out of the cell and K+ into the cell.

What would be expected to lower the Tm for a phospholipid bilayer?

replacing a lipid containing C18 fatty acids with one containing C16 fatty acids

Carbohydrate digestion begins with ______ in the ________. This enzyme hydrolyzes _______ to produce maltose, oligosaccharides, and glucose for around 1-2 hours before it is deactivated in the ________. When chyme reaches the duodenum, the ________ is stimulated to produce even larger quantities of this enzyme to continue digestion.

salivary amylase oral cavity starch stomach pancreas

Symport

same direction

In passive transport, the energy driving the movement of materials across a membrane is provided by

the concentration gradient across the membrane.

Although salts of fatty acids form micelles, phospholipids and glycolipids form bimolecular sheets due to

the presence of fatty acid acyl chains.

In the movement of small molecules across a lipid bilayer, the permeability coefficient can be correlated with

the solubility of the molecule in a nonpolar solvent.

What do micelles and chylomicrons have in common?

they both contain fatty acids

Enzymes that are activated by specific proteolytic cleavage are called

zymogens

The most common way in which integral membrane proteins span the membrane is in

α‑helical segments.