Exam 3 Flashcards

Vitamins and Signal Transduction

1
Q

What is the role of an enzyme cascade in a signal transduction?

A

Amplification

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Epinephrine binding to its receptors stimulates an increase in blood glucose levels, whereas insulin has the opposite effect. What term applies to a situation in which both hormones are bound to their receptors on the same cells?

A

Integration (the ability of the system to receive multiple signals and produce a unified response)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

An agonist is best defined as:

A) an effector molecule synthesized in a cell in response to an external signal such as a hormone.

B) a compound that interferes with the physiological action of another substance, usually at a hormone or neurotransmitter receptor.

C) a noncatalytic protein that holds together other protein molecules that function in concert.

D) a compound, typically a hormone or neurotransmitter, that elicits a physiological response when it binds at its specific receptor

A

B. a compound that interferes with the physiological action of another substance, usually at a hormone or neurotransmitter receptor.

Antagonists are molecules that bind a receptor without triggering the normal effect and thereby block the effects of agonists, including the natural ligand.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Which method could help determine what signaling system is likely stimulated through a receptor that binds a newly described nonsteroidal hormone?

A. tandem mass spectrometry

B. two-dimensional gel electrophoresis

C. ramachandran plot

D. hydropathy plot

A

D. hydropathy plot

Hydropathy analysis would predict seven membrane-spanning regions of the receptor molecule, suggesting the G-protein coupled signaling system.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Which statement describes the active form of the guanosine nucleotide-binding protein?

A. GTP binds the α subunit.

B. GDP binds the α subunit.

C. GTP binds the β subunit.

D. GDP binds the β subunit.

E. GTP binds the γ subunit.

A

A. GTP binds the α subunit.

The binding site for GDP or GTP is on the α subunit. When GTP is bound, the G protein is in its trimeric, active form.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which sequence correctly identifies the order of events that take place during desensitization of the β-adrenergic receptor? 1. binding of β-arrestin to the receptor

  1. recruitment of βARK to the membrane
  2. dissociation of Gsβγ from Gsα
  3. phosphorylation of Ser residues on the receptor

A. 2, 1, 4, 3

B. 3, 2, 4, 1

C. 1, 2, 4, 3

D. 4, 2, 1, 3

A

B. 3, 2, 4, 1

After epinephrine binds to the adrenergic receptor, Gsβγ dissociates from Gsα . Then, ARK associates with the receptor and phosphorylates Ser residues. β-arrestin binds to the phosphorylated receptor, leading to endocytosis of the receptor-arrestin complex.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Which molecule in signaling is NOT considered a second messenger?

A. calcium

B. GTP

C. inositol 1,4,5-triphosphate

D. cyclic AMP

A

B. GTP

GTP activates G proteins in GPCR signaling systems. However, GTP is not a second messenger. A second messenger is a low molecular weight metabolite or inorganic ion that activates or inhibits one or more downstream targets, often protein kinases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does PLC activate PKC?

A. It increases cAMP levels.

B. It converts phosphatidylcholine to phosphatidic acid, which activates PKC.

C. It converts phosphatidylcholine to DAG and phosphocholine to activate PKC.

D. It converts phosphatidylinositol-4,5-bisphosphate to diacylglycerol and IP3 to activate PKC.

A

D. It converts phosphatidylinositol-4,5-bisphosphate to diacylglycerol and IP3 to activate PKC.

The G protein (Gq ) acts through phospholipase C, which cleaves phosphatidylinositol 4,5-bisphosphate (PIP2 ) to diacylglycerol and IP3 . By opening Ca2+ channels in the endoplasmic reticulum, IP3 raises cytosolic [Ca2+]. Diacylglycerol and Ca2+ act together to activate protein kinase C, which phosphorylates and changes the activity of specific cellular proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Which process is NOT a feature of β-adrenergic receptors?

A. activate protein kinase A

B. interaction with β-arrestin

C. cause binding of Ca2+ to calmodulin

D. phosphorylation

A

C. cause binding of Ca2+ to calmodulin

Cellular [Ca2+] regulates (often through calmodulin) many enzymes and proteins involved in secretion, cytoskeletal rearrangements, and contraction. Many of the target enzymes are in the family of Ca2+-activated protein kinases (PKCs). This is distinct from signaling through βadrenergic receptors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How do BOTH major classes of G proteins become activated?

A. GTP is hydrolyzed to GDP.

B. GDP is phosphorylated.

C. GDP leaves the G proteins and GTP binds.

D. GDP binds after the α subunit dissociates from the δ and γ subunits.

A

C. GDP leaves the G proteins and GTP binds.

When an agonist binds to a G protein-coupled receptor, GDP is replaced with GTP on the G protein, activating the protein. In this active form, the G protein can transmit the signal from the activated receptor to its downstream effector protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Receptor tyrosine kinases:

A. bind two cAMPs when active.

B. do not regulate gene expression.

C. are not prone to dimerization.

D. autophosphorylate.

A

D. autophosphorylate.

Ligand binding activates tyrosine kinase activity by autophosphorylation. Autophosphorylation opens the active site so that the enzyme can phosphorylate Tyr residues of other target proteins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the connection between signaling through voltagegated ion channels, receptor tyrosine kinases, and microdomains (i.e., rafts)?

A. All are based on a conformational change in membrane proteins.

B. All are highly exergonic events.

C. All require increased concentrations of a second messenger.

D. All are stimulated through phosphorylation.

A

A. All are based on a conformational change in membrane proteins.

Voltage-gated ion channels, receptor tyrosine kinases, and microdomains all undergo a conformational change as part of their signaling system.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is unique about steroid receptor signaling?

A. It is the only one of the six signaling systems that has ligand receptors in the nucleus.

B. It is the only system used for hormone signaling.

C. It is the only one of the six signaling systems that stimulates a change in gene expression.

D. It is the only system that does not use second messenger molecules

A

A. It is the only one of the six signaling systems that has ligand receptors in the nucleus.

In target cells, steroid hormones pass through the plasma membrane and nuclear membrane by simple diffusion and bind to specific receptor proteins in the nucleus. The hormone-receptor complex binds specific regions of DNA at the hormone response elements and interacts with other proteins to regulate the expression of nearby genes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

When a cell exists the quiescent phase, which phase does it immediately enter?

A. S

B. M

C. G1

D. G2

E. G0

A

C. G1

After passing through mitosis and into G1, a cell either continues through another division or ceases to divide, entering a quiescent phase (G0) that may last hours, days, or the lifetime of the cell. When a cell in G0 begins to divide again, it reenters the division cycle through the G1 phase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which statement is false?

A. Oncogenes are genetically dominant.

B. Oncogenes are mutated versions of proto-oncogenes.

C. The proteins pRb, p53, and p21 derive from tumor suppressor genes.

D. Tumor suppressor genes encode defective signaling proteins.

A

D. Tumor suppressor genes encode defective signaling proteins.

Oncogenes encode defective signaling proteins. Tumor suppressor genes encode regulatory proteins that normally inhibit cell division.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Considering the various types of genes associated with the formation of cancers, mutations in which gene groups would MOST LIKELY have the greatest contribution to the formation of a cancer?

A. genes stimulating cell growth

B. genes involved in DNA damage repair

C. genes inhibiting cell growth

D. genes involved in cell cycle progression

A

B. genes involved in DNA damage repair

Cancer is generally the result of an accumulation of mutations in oncogenes and tumor suppressor genes. Thus, mutations in genes involved in DNA damage repair would likely allow these mutations in oncogenes and tumor suppressor genes to accumulate and cause cancer.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Vitamin A

A
  • Characteristics: Nonpolar, Hormone precursor
  • Chemical Name: Retinol
  • Biological Process: Derives Retinoic acid and all-trans retinal, which is essential in the activation of rhodopsin in the vertebrate eye
  • Source: Orange vegetables (beta-carotene), Fish liver oils, Eggs, Milk, Butter
  • Deficiency: Dry skin, Hindered neuronal development, night blindness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Vitamin D

A
  • Characteristics: Nonpolar, Hormone Precursor
  • Chemical Name: Cholecalciferol
  • Biological Process: Regulates calcium uptake in the intestines, kidneys, and bones
  • Source: Formed in the skin from the photochemical 7-dehydrocholesterol driven by UV radiation
  • Deficiency: Rickets, soft bones, osteoporosis, and seasonal depression
  • Only vitamins where a slight deficiency can have an effect (usually the only deficiencies seen in a first world country)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Vitamin E

A
  • Characteristics: Nonpolar, Oxidation Reduction Cofactors
  • Chemical Name: Tocopherols
  • Biological Process: Biological antioxidant. Associates with the cell membrane, lipid deposits, and lipoproteins in the blood.
  • Source: Eggs and vegetable oils
  • Deficiency: Scaly skin, muscle weakness, sterility, fragile erythrocytes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Vitamin K

A
  • Characteristics: Nonpolar, Oxidation Reduction Cofactors
  • Chemical Name: Phylloquinone
  • Biological Process: Undergoes a cycle of oxidation and reduction during the formation of prothrombin (blood plasma protein). Essential for blood clotting. Converts fibrinogen to fibrin.
  • Source: Green plants and bacteria
  • Deficiency: Slows the body’s ability to clot. Fatal.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Vitamin C

A
  • Characteristics: Polar, Antioxidant Enzyme cofactor
  • Chemical Name: L-Ascorbic Acid
  • Biological Process: Cofactor in at least 8 enzymatic reactions. Essential in collagen synthesis
  • Source: Fruits and Vegetables
  • Deficiency: Scurvy, Dysfunctional collagen, Spongy gums, Bleeding from mucous membranes, and brown spots on skin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Vitamin B1

A
  • Characteristics: Polar, Nitrogen containing
  • Chemical Name: Thiamine
  • Biological Process: Plays a central role in the generation of energy from carbohydrates. Involved in the conversion of pyruvate to acetyl coenzyme A in metabolism.
  • Source: Synthesized in bacteria, fungi, and plants.
  • Deficiency: Beriberi, Wernicke’s encephalopathy, Korsakoff’s syndrome
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Vitamin B2

A
  • Characteristics: Polar, Nitrogen containing
  • Chemical Name: Riboflavin
  • Biological Process: Involved in energy production for the electron transport chain, the citric acid cycle, and the catabolism of fatty acids.
  • Source: Milk, eggs, cheese, leaf vegetables, liver, kidneys, legumes, mushrooms, almonds.
  • Deficiency: Ariboflavinosis, UV sensitivity, Cheilosis, Pseudo-syphilis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Vitamin B3

A
  • Characteristics: Polar, Nitrogen containing
  • Chemical Name: Niacin (Nicotinic Acid and Nicotinamide)
  • Biological Process: Coenzymes forms NAD and NADP. Plays an important role in energy transfer reactions in the metabolism of glucose, fat, and alcohol
  • Source: Synthesized from tryptophan. Liver, chicken, beef, fish, cereal, peanuts, and legumes.
  • Deficiency: Pellagra, Nausea, Skin and mouth lesions, Anemia, Headaches, Tiredness
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Vitamin B5

A
  • Characteristics: Polar, Nitrogen containing
  • Chemical Name: Pantothenic Acid
  • Biological Process: Required in the synthesis of Coenzyme A, synthesis, and metabolism of proteins, carbohydrates, and fats.
  • Source: Most foods
  • Deficiency: Acne and Paresthesia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Vitamin B6

A
  • Characteristics: Polar, Nitrogen Containing
  • Chemical Name: Pyridoxine
  • Biological Process: Coenzyme in many enzymatic reactions: Amino acid metabolism, hemoglobin synthesis and function, glucose metabolism, gene expression, lipid metabolism.
  • Source: Widely distributed in foods. Pork, turkey, beef, bananas, chickpeas, potatoes, and pistachios
  • Deficiency: Seborrheic dermatitis-like eruptions, Atrophic glossitis with ulceration, Angular cheilitis, conjunctivitis, Intertrigo, and neurological symptoms
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Vitamin B7

A
  • Characteristics: Polar, Nitrogen containing
  • Chemical Name: Biotin
  • Biological Process: A coenzyme for carboxylase enzymes; involved in the synthesis of fatty acids, isoleucine, and valine; involved in gluconeogenesis
  • Source: Intestinal bacteria, peanuts, Swiss chard, leafy green vegetables, raw egg yolk, liver, and Saskatoon berries
  • Deficiency: Brittle/thin fingernails, alopecia, conjunctivitis, dermatitis, and neurological symptoms in adults
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Vitamin B9

A
  • Characteristics: Polar, Nitrogen Containing
  • Chemical Name: Folic Acid
  • Biological Process: Required in DNA synthesis, DNA repair, and DNA methylation. Cofactor in certain biological reactions (important in rapid cell division and growth, required for healthy red blood cell production and anemia prevention)
  • Source: Dark leafy green vegetables, fruits, nuts, beans, peas, dairy products, poultry and meat, eggs, seafood, grains, and some beers. Most common in avocado, beetroot, spinach, liver, yeast, asparagus, and Brussel sprouts (used as a prenatal supplement)
  • Deficiency: Neural tube defects in developing embryos, diarrhea, nerve damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Vitamin B12

A
  • Characteristics: Polar, Nitrogen containing
  • Chemical Name: Cobalamin
  • Biological Process: Key role in the normal function of the brain and nervous system. Key role in red blood cell synthesis. Involved in the metabolism of every cell in the human body. Used to treat cyanide poisoning
  • Source: Only bacteria and archaea have the enzymes for synthesis, Bacterial flora, some plants due to bacterial symbiosis
  • Deficiency: severe and irreversible damage (especially to the brain and nervous system) → symptoms include fatigue, depression, and poor memory.
  • Vitamins where a slight deficiency can have an affect
30
Q

What are vitamins?

A
  • Compound that are essential to the health of vertebrates
  • cannot be synthesized in the body (must be obtained through the diet)
  • Two major classes:
    • Fat Soluble Vitamins (Nonpolar)
    • Water Soluble Vitamins (polar)
31
Q

Warfarin

A
  • Anticoagulant drug
  • Vitamin K antagonist
  • Inhibits the formation of active prothrombin
  • Patients taking warfarin must regulate the amounts of greens the consume due to Vitamin K content
32
Q

Signal Trandsuction

A
  • the conversion of information into a chemical change
33
Q

Signal Transduction: Principle 1

A
  • cells respond to external signals through receptor mediated processes that amplify the signal, integrate it with input from other receptors, transmit the signal to the appropriate effectors, and eventually the end of the response
34
Q

Signal Transduction: Principle 2

A
  • There is a high degree of evolutionary conservation of signaling proteins and transduction mechanisms across the animal phyla
35
Q

Signal Transduction: Principle 3

A
  • In multicellular animals, GPCRs with seven transmembrane helices are the largest group of plasma membrane receptors.
36
Q

Signal Transduction: Principle 4

A
  • Plasma membrane receptors with an intracellular tyrosine kinase activity act trough cascades of protein kinases to transduce signals about the metabolic state, including growth factors.
37
Q

Signal Transduction: Principle 5

A

Phosphorylation of intrinsically disordered regions of signaling proteins acts as a switch, toggling enzyme activity or creating binding sites for other molecules.

38
Q

Signal Transduction: Principle 6

A
  • Ion channels gated by membrane potential or ligands are central to signaling in all cells, including bacteria, plants and animals.
39
Q

Signal Transduction: Principle 7

A
  • Some hormone signals act inside the cel, not at the plasma membrane, forming complexes with specific receptor proteins that regulate gene expression.
40
Q

Signal Transduction: Principle 8

A
  • Cells receive extracellular signals that determine progress through the cell division cycle, or triggered cell death- processes regulated by phosphorylation and dephosphorylation of key regulatory proteins
41
Q

Signal Transduction: Principle 9

A
  • Defective signaling proteins or defective regulation of their synthesis and breakdown can disrupt cell cycle regulation and lead to tumor formation (cancer).
42
Q

Specificity

A
  • Achieved by precise molecular complementarity
    • mediated by weak (noncovalent) forces
43
Q

Amplification

A
  • Results when an enzyme is activated by a signal receptor and, in turn, catalyzes the activation of many molecules of a second enzyme, and so on, in an enzyme cascade
44
Q

Modular

A
  • Has multiple domains that recognize specific features
    • allows cells to mix and match a set of signaling molecules
45
Q

Scaffolding Proteins

A
  • nonenzymatic proteins that bring together enzymes that interact in cascades
46
Q

Desensitized

A
  • no longer responsive to a signal
    • occurs when a signal is present continuously
47
Q

Integration

A
  • the ability of the system to receive multiple signals and produce a unified response
48
Q

Divergent

A
  • Branched rather than linear
    • Occurs when a signal is present continuously
49
Q

Response Localization

A
  • cells confine signaling system components to a structure to regulate processes locally
50
Q

Examples of Signals that Cells can Respond To

A
  • Antigens
  • Odorants
  • Tastants
  • Pheromones
  • Hypoxia
  • Light
  • Growth Factors
  • Neurotransmitters
  • Mechanical Touch
51
Q

Conserved elements of animal signaling systems

A
  • Receptors in membrane have 7TM helices
  • G proteins that bind GTP or GDP and interface with the membrane receptors
  • Ca2+ -binding proteins
  • Ca2+ -dependent protein kinases
  • Protein kinases that areactivated during cell division
  • Nonenzymatic protein scaffolds that bring modules together
  • Protein kinases that phosphorylate GPCR receptors
  • Membrane xprotein kinases
  • Cyclic nucleotide-depedednt protein kinases
52
Q

4 General Types of Signal Transducers

A
  • G protein-coupled receptor
  • Receptor Enzyme (TKs)
  • Gated Ion Channels
  • Nuclear Receptors
53
Q

G Protein-Coupled Receptors (GPCRs)

A
  • receptors that act through a member of the guanosine nucleotide-binding protein (G protein) family.
  • largest group of plasma membrane receptors in multicellular animals
  • G protein cycles between active (GTP-bound) forms and inactive (GDP-bound)
  • An effector enzyme (or ion channel) in the plasma membrane that is regulated by the activated G protein
54
Q

Adrenergic receptors

A
  • protein receptors in the plasma membrane that bind epinephrine
    • 4 general types: α1 , α2 , β1 , β2
55
Q

Agonists

A
  • Molecule that binds a receptor and produces the effects of the ligand
56
Q

Antagonist

A
  • Analog that binds teh receptor and blocks the effects of the agonist, including the natural ligand
57
Q

The β-Adrenergic Pathway

A
  • hormone-boung GPCR acts as a guanosine nucleotide-exchange factor (GEF)
  1. Epi binds to its specific receptor
  2. Allosteric change in hormone-receptor complex causes the GDP bound to Gsa to be replaced with GTP, activating Gsa
  3. Activted Gsa seperated from GsBsY, moves to AC and activates it. Many Gsa subunits may be activated by one occupied receptor.
  4. AC (integral protein) catalyzes the synthesis of cAMP from ATP when associated with active Gsa
  5. cAMP activates PKA
  6. Phosphorylation of cellular proteins by PKA causes the cellular response to epinephrine
58
Q

GTPase Switch

A
  • Gsa has intrinsic GTPase activity that switches Gsa to its inactive form by converting GTP to GDP
59
Q

Protein Kinase A

A
  • cAMP-dependent protein kinase (PKA)
  • Catalyzes the phosphorylation of specific Ser or Thr residues of target proteins
60
Q

Epinephrine Cascade

A
  • the cascade amplifies the hormonal signal by orders of magnitude
    • this accounts for the low levels of epi required for activity
  • The signal leads to intracellular changes within fractions of a second
61
Q

Several Mechanisms Cause Termination of the β-Adrenergic Response

A
  • epi concentration drops below the Kd for its receptor
  • the GTPase activity of the G protein hydrolyzes the GTP bound to the Ga subunit
  • cAMP is hydrolyzed to 5’AMP by cyclic nucleotide phosphodiesterase
    *
62
Q

Phosphoprotein Phosphatase

A
  • enzyme that hydrolyzes phosphorylated Tyr, Ser, or Thr residues, releasing inorganic phosphate (Pi)
    • this reverses the metabolic effects that result from PKA activity
63
Q

G Protein Coupled Receptor Kinases (GRKs)

A
  • protein family that phosphorylates GPCRs on their carboxyl-terminal cytoplasmic domains and plays a role similar to that of βARK in receptor desensitization and resensitization
    *
64
Q

Phospholipase C

A
  • catalyzes cleavage of the membran phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2) → diacylglycerol adn inositol 1,4,5-triphosphate (IP3) which are potent 2nd messengers
65
Q

How does inhibitory G protein (Gi) inhibit adenylyl cyclase and lower [cAMP]?

A

Gi is structually homologous to Gs but is activated by the binding of somatostatin to its receptor

66
Q

Oncogenes

A
  • mutated versions of genes encoding signaling proteins in cell cycle regulation
    • lead to tumor formations
    • genetically dominant
    • may encode defective growth factors, receptors, G proteins, protein kinases, or nuclear regulators of transcription
67
Q

Proto-oncogenes

A
  • genes in animal host cells the encode growth-regulating proteins
68
Q

Tumor Suppressor Genes

A
  • encode regulatory proteins that normally inhibit cell division
    • mutations in these genes are genetically recessive
69
Q

Stability Genes (Caretaker Genes)

A
  • encode proteins necessary for the repair of genetic damage
    • mutations cause other mutations to go unrepaired
    • can cause cancer when the unrepaired mutations are proto-oncogened and tumor suppressor genes
70
Q

Driver Mutations

A
  • mutations that are the cause of unregulated cell division
71
Q

“Passenger Mutations”

A
  • mutations that occur randomly and do not confer a selective growth advantage
72
Q

What are the complexes involved in RTK signaling (in order from ligand binding)?

A

ligand → dimerization of a and B RTK subunits → IRS1 → SH2 domain of Grb2 → SOS → Ras → Raf-1 → MEK → ERK → Transcription factors in nucleus