Exam 2

• ______: End oxidation of carbohydrates; fatty acid oxidation; O₂ consumption; ATP synthesis by oxidative phosphorylation.

• Mitochondria

• _______: Protein synthesis.

• Ribosomes

_______: “Secretory pathway”; synthesis of membrane lipids, membrane proteins, and secreted proteins.

ER and Golgi

______: Many biosynthetic pathways; initial catabolism of monosaccharides; storage of glycogen and fat.

Cytoplasm

______: Digestion of endocytosed and phagocytosed materials.

Lysosomes

_______: Specialized reactions that form hydrogen peroxide (H₂O₂) as a byproduct.

Peroxisomes

Which organelle contains hydrolytic enzymes that function best in acidic environments and are essential for intracellular digestion?

Lysosome

______: Synthesis of ribosomal RNA (rRNA) and assembly of ribosomal subunits.

Nucleolus

_______: Central databank; DNA and RNA synthesis

Nucleus

What the the DNA level or metabolic pathways?

• Amount of enzyme is adjusted by change in its synthesis/degradation 

• It is LONG TERM

What is the protein level of metabolic pathways?

• Modified covalently by de-/phosphorylation 

• it is short term

What is the ATP level of metabolic pathways?

• Metabolic enzymes can be regulated by allosteric effectors (substrate, intermediate, or product of pathway)

• Allosteric Effectors - a molecule that binds to an enzyme or protein at a site other than the active site, changing its shape and activity

Of the three metabolic pathways, which is the fastest?

Allosteric effectors (ATP) level are the fastest

Of the three metabolic pathways, which is the slowest?

Long-term (DNA level) - this is due to the lifespand of the metablic enzyme ranging from 1 hr - days

Of the three metabolic pathways, which is the second fastest?

• short term (protein level)

• requires protein kinase and protein phosphatase

What do protein Kinases do?

Attach a phosphate group

What do protein Phosphatase do?

Remove a phosphate group

What is phosphoylation?

Formation of a phosphate derivative

What is dephosphoylation?

removale of a phosphate groups

_______ pathway: Regulation by feedback inhibition

Anabolic pathway

_______ pathway: regulation by ATP and ADP. Pi, inorganinc phosphate

catabolic

_________ pathway: regulation by feedworward stimulation

Catabolic pathway

Regulation pathways: traits of the anablic pathway (feedback inhibition)?

• the end product inhibits an earlier enzyme

• This prevents the cell from making more product when enough has accumulated

Regulation pathways:traits of the catabolic pathway (regulation by ATP, ADP, and Pi)

• Reflects the cells energy status

• High ATP → generally slows catabolic pathways because energy is plentiful

• High ADP/Pi (and often AMP) → generally stimulated catabolism because more ATP is needed

Regulation pathways: catabolic pathways → feedforward stimulation

• an earlier metabolite activates an enzyme later in the pathway.

• This prepares downstream rections to handle incoming metabolites

In an anabolic pathway, the final product accumulates and binds to an enzyme that acts early in the pathway, decreasing its activity. What type of regulation is occurring?

A. Feedforward stimulation
B. Feedback inhibition
C. Substrate-level phosphorylation
D. Energy-charge regulation
E. Competitive activation

Answer: B. Feedback inhibition

The end product feeds back and inhibits an earlier step, preventing unnecessary production.

When Z reaches a high concentration, it inhibits the enzyme responsible for converting A → B. What is the primary advantage of this regulation?

A. It increases ATP production
B. It accelerates breakdown of Z
C. It prevents unnecessary synthesis of Z
D. It increases the concentration of B
E. It stimulates catabolic pathways

C. It prevents unnecessary synthesis of Z

This is feedback inhibition: enough final product → shut down an earlier step.

A cell has a high ATP concentration and low ADP concentration. What would most likely happen to a catabolic pathway responsible for producing ATP?

A. Its activity would increase
B. Its activity would decrease
C. It would switch to an anabolic pathway
D. ADP would inhibit the pathway
E. ATP would have no regulatory effect

Answer: B. Its activity would decrease

High ATP = plenty of energy, so there is less need for ATP-producing catabolic pathways.

During intense exercise, ATP is rapidly consumed and ADP and Pi concentrations increase. What effect would this most likely have on ATP-producing catabolic pathways?

A. Inhibit them
B. Have no effect on them
C. Stimulate them
D. Convert them into anabolic pathways
E. Cause feedback inhibition by ATP

Answer: C. Stimulate them

↑ ADP/Pi = energy demand is high → stimulate catabolism → produce more ATP.

In a catabolic pathway:

A → B → C → D → E

An increase in B activates the enzyme responsible for converting D → E. What type of regulation is this?

A. Feedback inhibition
B. Competitive inhibition
C. Feedforward stimulation
D. Product inhibition
E. Energy-charge inhibition

Answer: C. Feedforward stimulation

An earlier metabolite stimulates a later step, preparing the pathway for increased incoming material.

Which scenario best represents feedforward stimulation?

A. ATP inhibits an enzyme in glycolysis when ATP levels are high.
B. The final product of a biosynthetic pathway inhibits its first committed step.
C. ADP stimulates a pathway that generates ATP.
D. An early intermediate activates an enzyme that functions later in the same pathway.
E. A final product activates the enzyme that produced it.

Answer: D. An early intermediate activates an enzyme that functions later in the same pathway.

_________: later product → inhibits earlier step.

Feedback inhibition

_______________: earlier metabolite → stimulates later step.

Feedforward stimulation

what type of pathway is this?

it is an anabolic pathway via feedback inhibition

A → B → C → etc. (its continously adding products) = anabolic

The end product is stopping the start = feedback inhibiton

What type of pathway is this?

since its being broken down into smaller peices (CO2 and H20) = catabolic

Regulated by ATP, ADP, and Pi. High ATP inhibits the pathway, while high ADP + Pi stimulates it.

Q: What does a high ADP level indicate about the cell?

A: The cell is in a low-energy state and needs to produce more ATP.

Q: How does increased ADP generally affect catabolic pathways?

A: Stimulates catabolism → increases fuel breakdown to generate ATP.

Q: How does increased ADP generally affect anabolic pathways?

A: Decreases/favors slowing anabolism because anabolic pathways require energy, which is currently limited.

Q: What does a high ATP level indicate about the cell?

A: The cell is in a high-energy state and has abundant energy available.

Q: How does increased ATP generally affect catabolic pathways?

A: Inhibits catabolism because the cell does not need to produce as much additional ATP.

Q: How does increased ATP generally affect anabolic pathways?

A: Favors anabolism because sufficient energy is available for biosynthesis.

Q: What is the general relationship between cellular energy status and metabolism?

• ↑ ADP/AMP → ↑ catabolism, ↓ anabolism

• ↑ ATP → ↓ catabolism, favors anabolism

what type of pathway is the following?

we know it is catabolic because it is being broken down

since an early metabolite is stimulating the next step, we know ots feedforward

high ATPs role on pathways

High ATP:

Favors anabolic pathways (Activates)

does not favor catabolic pathways (Inhibits)

high ADPs role on pathways

High ADP:

Favors catabolic pathways (activates)

Does not favor catabolic pathways (inhibits)

When is insulin produced?

After carbohydrate-rich meal

When is Glucagon produced?

During fasting

When is norepinephrine/noepinephrine produced?

During acute stress & physical exertion

When is cortisol produced?

during prolonged stress

function of insulin?

Stimulates utilization of dietary nutrients

function of glucagon?

Maintains blood glucose levels

function of Epinephrine & Norepinephrine?

Stipulates mobilization of glucose from glycogen and utilization of stored fat

function of cortisol?

Promotes glucose synthesis & fat breakdown

Enzyme deficiancy pathways:

Anabolic pathways?

Lack of product causes clinical signs/symptoms to manifest (Metabolite C accumulates, product is deficient)

What kind of defiancy pathway is the following?

Anabolic Pathway: Lack of product causes clinical signs/symptoms to manifest (Metabolite C accumulates, product is deficient) 

Enzyme deficiancy pathways:

Catabolic pathways?

Catabolic Pathway: Depends on where deficient enzyme is in pathway; Deficiency of an enzyme in a major, ATP-producing catabolic pathway causes serious problem to cells that depend on pathway for energy.

What kind of defiancy pathway is the following?

When there is an accumulation of nutrient (less toxic) or its metabolites (more toxic)

Other nutrients may still be catabolized to yield ATP

Catabolic

What kind of defiancy pathway is the following?

Catabolic Pathway: Depends on where deficient enzyme is in pathway; Deficiency of an enzyme in a major, ATP-producing catabolic pathway causes serious problem to cells that depend on pathway for energy.

A ________ is a disorder where a cell cannot properly break down or process a certain substance (usually macromolecules), so that substance accumulates (is “stored”) inside the cell.

storage disease

Enzyme deficiancy pathways:

Degredation of a macromolecules

The undegraded molecule C accumulates, mostly within the cells resulting in a storage disease.

What is the enzyme deficiancy is the following?

Degradation of a Macromolecule: The undegraded molecule C accumulates, mostly within the cells resulting in a storage disease.

Pathophysiology of vitamin defiancies?

Limits production of vitamin-derived coenzymes (NAD, FAD, CoA)  

Pathophysiology of toxins (cyanide)?

Inhibition of metabolic enzymes: mitochondrial cytochrome oxidase

Pathophysiology of endocrine d/o: Diabetes?

Insufficient insulin action 

effect of vitamin deficiencies?

Metabolic pathways are deprived of essential coenzymes 

effect of Toxins: Cyanide?

Blocks cell respiration 

effect of diabetes?

Disruption of pathways in carbohydrates & fat metabolism

Which type of metabolic regulation is considered the fastest in response to changes in metabolic pathways?

a) Protein synthesis or degradation at the DNA level

b) Allosteric effector binding to enzymes

c) Phosphorylation by kinases

d) Dephosphorylation by phosphatases

e) Transcription factor activation

b) Allosteric effector binding to enzymes

traits of glucose

1. Most abundant monosaccharide in diet

2. Made from other monosaccharides

3. Made by breaking down glycogen (storage polysaccharide)

4. Made from amino acids & other non-carb structures 

traits of glucose transport

Glucose is not sufficiently lipid soluble to enter cells via simple diffusion (“passive” transport) across the plasma membrane

Glucose is bulky and tends to form H+ bonds (hydrophilic).

How does dierary glucose enter interstitial mucosa?

via sodium cottransport (“facilitated diffusion”) 

Q: How does dietary glucose enter intestinal mucosal cells?

A: Through Na⁺-glucose cotransport (SGLT), driven by the Na⁺ concentration gradient.

Q: What drives Na⁺-glucose cotransport in the intestine?

A: Na⁺ moving down its concentration gradient from high Na⁺ outside → low Na⁺ inside the intestinal cell. This movement provides the energy to bring glucose into the cell.

Q: What maintains the Na⁺ gradient needed for intestinal glucose absorption?

A: The Na⁺/K⁺ ATPase, which uses ATP to pump Na⁺ out of the cell, keeping intracellular Na⁺ low.

Q: How does glucose leave the intestinal cell and enter the blood?

A: Through GLUT2 by facilitated diffusion, moving glucose down its concentration gradient.

Q: What is the key difference between dietary glucose transport and circulatory glucose transport?

• Dietary glucose: enters intestinal cells through Na⁺-glucose cotransport (SGLT).

• Circulatory glucose: enters cells through GLUT transporters by facilitated diffusion.

Steps of fascilitated diffusion of glucose?

1. Glucose binds to the transport protein (GLUT) 

2. Binding of glucose causes conformational change. 

3. Glucose dissociates from the transport protein and is released. 

4. Transport protein returns to its original conformation.

How does glucose move?

It moves down its concentration gradient and does not require ATP

(glucose binding itself causes the transporter to change shape.)

Dietary glucose in the intestinal lumen is absorbed into an intestinal mucosal cell primarily through which mechanism?

A. Simple diffusion through the lipid bilayer
B. GLUT2-mediated facilitated diffusion
C. Na⁺-glucose cotransport through SGLT
D. Na⁺/K⁺ ATPase-mediated glucose transport
E. ATP-dependent glucose pumping

Answer: C. Na⁺-glucose cotransport through SGLT

Why: SGLT uses the Na⁺ concentration gradient to bring Na⁺ and glucose into the intestinal cell together.

What directly provides the driving force for glucose uptake through the intestinal Na⁺-glucose cotransporter?

A. Hydrolysis of ATP by SGLT
B. Movement of K⁺ down its concentration gradient
C. Movement of Na⁺ down its concentration gradient
D. Movement of glucose down its concentration gradient
E. Hydrolysis of GTP

Answer: C. Movement of Na⁺ down its concentration gradient

Inhibition of the Na⁺/K⁺ ATPase in an intestinal epithelial cell would eventually decrease dietary glucose absorption because:

A. GLUT2 requires ATP directly
B. Intracellular Na⁺ would increase, reducing the Na⁺ gradient
C. Extracellular glucose concentration would decrease
D. SGLT would begin pumping glucose out of the cell
E. Intracellular K⁺ would increase and inhibit GLUT2

Answer: B. Intracellular Na⁺ would increase, reducing the Na⁺ gradient

After glucose enters an intestinal mucosal cell through SGLT, how does it primarily leave the cell and enter the bloodstream?

A. Na⁺/glucose cotransport
B. Simple diffusion
C. Na⁺/K⁺ ATPase
D. GLUT2-mediated facilitated diffusion
E. Primary active transport

Answer: D. GLUT2-mediated facilitated diffusion

Which statement best distinguishes the transport of dietary glucose from the transport of glucose already present in the circulation?

A. Both require Na⁺ cotransport to enter cells
B. Dietary glucose uses SGLT in intestinal absorption, whereas circulating glucose generally uses GLUT transporters
C. Dietary glucose uses GLUT2 to enter intestinal cells from the lumen
D. Circulating glucose requires direct ATP hydrolysis by GLUT transporters
E. Dietary glucose crosses the intestinal membrane by simple diffusion

Answer: B. Dietary glucose uses SGLT in intestinal absorption, whereas circulating glucose generally uses GLUT transporters

A mutation causes the Na⁺/K⁺ ATPase of an intestinal epithelial cell to become significantly less active. Which sequence of changes would be expected?

A. ↓ intracellular Na⁺ → ↑ Na⁺ gradient → ↑ glucose absorption
B. ↑ intracellular Na⁺ → ↓ Na⁺ gradient → ↓ SGLT-mediated glucose uptake
C. ↑ intracellular Na⁺ → ↑ Na⁺ gradient → ↑ glucose absorption
D. ↓ intracellular Na⁺ → ↓ GLUT2 activity → ↓ glucose absorption
E. ↑ intracellular K⁺ → ↑ SGLT-mediated glucose uptake

Answer: B. ↑ intracellular Na⁺ → ↓ Na⁺ gradient → ↓ SGLT-mediated glucose uptake

pathway of Na+/K+ ATPase intracellularly

Na⁺/K⁺ ATPase keeps intracellular Na⁺ LOW → creates Na⁺ gradient → Na⁺ enters through SGLT → glucose comes with it.

A glucose molecule enters a cell through a GLUT transporter by facilitated diffusion. Which event occurs immediately after glucose binds to the transporter?

A. ATP is hydrolyzed
B. The transporter undergoes a conformational change
C. Glucose is phosphorylated
D. The transporter is degraded
E. ADP binds to the transporter

Answer: B. The transporter undergoes a conformational change

Which statement best describes glucose transport by facilitated diffusion?

A. Glucose moves against its concentration gradient using ATP
B. Glucose crosses directly through the lipid bilayer without a protein
C. Glucose moves down its concentration gradient with the assistance of a membrane transport protein
D. ATP binding causes glucose to move through the transporter
E. Glucose movement requires phosphorylation of the transporter

Answer: C. Glucose moves down its concentration gradient with the assistance of a membrane transport protein

A mutation allows a glucose transporter to bind glucose normally but prevents the transporter from undergoing a conformational change. What would most likely occur?

A. Glucose would still cross normally because ATP provides the necessary energy
B. Glucose would be unable to efficiently cross the membrane through this transporter
C. Glucose would begin moving against its concentration gradient
D. The transporter would convert glucose into ATP
E. Glucose would diffuse directly through the lipid bilayer at the same rate

Answer: B. Glucose would be unable to efficiently cross the membrane through this transporter

A researcher observes glucose moving through a membrane protein from an area of high glucose concentration to an area of low glucose concentration. The membrane protein repeatedly changes conformation during transport, but ATP consumption does not increase. Which mechanism best explains this observation?

A. Primary active transport
B. Secondary active transport
C. Simple diffusion
D. Facilitated diffusion
E. Endocytosis

Answer: D. Facilitated diffusion

Which change would most directly prevent a GLUT transporter from completing one cycle of facilitated glucose transport?

A. Preventing ATP hydrolysis
B. Preventing ADP formation
C. Preventing glucose from binding to the transporter
D. Increasing intracellular ATP
E. Increasing mitochondrial ATP production

Answer: C. Preventing glucose from binding to the transporter

Which sequence correctly describes facilitated diffusion of glucose?

A. ATP hydrolysis → glucose binding → conformational change → glucose release
B. Glucose binding → ATP hydrolysis → glucose release → conformational change
C. Glucose binding → conformational change → glucose release → transporter returns to original conformation
D. Conformational change → ATP binding → glucose binding → glucose release
E. Glucose phosphorylation → glucose binding → ATP hydrolysis → glucose release

Answer: C. Glucose binding → conformational change → glucose release → transporter returns to original conformation

Q: What drives glucose transport by facilitated diffusion, and why does it not require ATP?

A: The glucose concentration gradient drives transport. Glucose moves from high → low concentration through a GLUT transporter, so ATP is not required.

GLUT1 is expressed where?

most tissues

what is the function of GLUT1?

Basal glucose uptake

 

GLUT2 is expressed where?

Liver, intestine, pancreatic β-cells

Function of GLUT2?

High-capacity glucose uptake 

GLUT3 is expressed where?

Brain

GLUT3 function

Neuronal glucose uptake

Where is GLUT4 location?

Muscle, adipose tissue, heart

GLUT4 function

Insulin-dependent glucose uptake