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Biochemistry Block 2 > Cell Signaling > Flashcards

Cell Signaling Flashcards

1
Q

Which glucose transporter is regulated by insulin?

Where does it transport glucose to?

A

GLUT4

Muscle and adipose tissue

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2
Q

When G protein coupled receptor binds to a ligand, conformational change occurs that causes?

A

Signals to be transmitted to the interior of the cell

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3
Q

Is GTP active or inactive?

GDP?

A

GTP is active, GDP is inactive

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4
Q

What type of reaction converts GTP to GDP and Pi?

Which subunit does this?

Why is this important?

A

Hydrolysis

G alpha

If it did not have the ability hydrolyze to GDP, it would always be activated which is not good

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5
Q
  1. When G alpha is activated it interacts with ___ and is bound to?
  2. When G alpha is inactivated it interacts with ___ and is bound to?
A
  1. Adenylyl cyclase; GTP

2. A specific activated GPCR (G protein coupled receptor); GDP

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6
Q

What determines if a G protein functions to stimulate or inhibit adenylyl cyclase?

A

Its dependent on which family of G protein is linked to GPCR in a cell type

~G alpha s or G alpha i

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7
Q

What is adenylyl cyclase and what does it do and how does it do it?

A

An integral membrane enzyme that generates cAMP by using energy from hydrolysis of ATP -> AMP + PPi (works quickly)

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8
Q

What is cAMP classified as?

A

The secondary messanger in the cell

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9
Q

What is the target of cAMP?

One example?

A

Family of enzymes called cAMP dependent protein kinases

Protein kinase A

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10
Q

What is protein kinase A composed of?

General mechanism of cAMP?

A

2 regulatory subunits and 2 catalytic subunits

CAMP gets generated and binds regulatory subunit of protein kinase A which releases the catalytic subunit, leading to phosphorylation

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11
Q

What do active protein kinase A catalytic subunits do?

What is the purpose of phosphorylation?

A

Phosphorylate target proteins and enzymes to elicit the desired function in cell (phosphorylate intracellular effectors)

Phosphorylate in order to elicit a cellular response; it is a modified state that does not necessarily mean its activated

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12
Q

Summary slide for initiating a cellular response to extracellular signals (7 steps)

A
  1. Extracellular ligand binds to receptor on target cell
  2. Receptor adopts conformational change that is transmitted to the inside of the cell
  3. GDP: G protein interacts with activated receptor which causes G alpha subunit to change conformation; new conformation causes G alpha to exchange GDP to GTP then G alpha dissociates from the beta and gamma subunits
  4. GTP: G alpha subunit interacts with and activates adenylyl cyclase
  5. Adenylyl cyclase adopts an active conformation and generates cAMP from ATP
  6. GTP: G alpha hydrolyzes GTP to GDP, dissociates from adenylyl cyclase
  7. GDP: G alpha docks with beta and gamma subunits
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13
Q

Name 3 intracellular effectors and what they regulate

A
  1. Ion channels - regulate the flow of specific ions across membranes (a lot in kidney)
  2. Enzymes - regulate metabolic pathways
  3. DNA binding proteins - regulate gene expression (important for cell differentiation)
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14
Q

Does phosphorylation positively or negatively affect the activity of an intercellular effector

A

It can do either

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15
Q

What do protein phosphatases do?

Name 3 AAs that are involved with this

A

Enzymes that remove effector proteins that are phosphorylated by protein kinases (so when hormone signals go away, this enzyme will change things back to inactive status)

Serine, threonine, and tyrosine

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16
Q

What is the function of cAMP phosphodiesterase?

A

Rapidly converts cAMP to 5’-AMP which is not a signaling molecule; turning it back to inactive status

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17
Q

Vibrio cholerae is a bacteria that has what effect on the body?

Treatment?

Why is this relevant?

A

It secretes cholera toxin which eventually leads to ribosylation of G alpha stimulatory which is permanently active. So there is a continuous activity of adenylyl cyclase and production of cAMP

Water and electrolyte replacement to treat dehydration and electrolyte imbalance

It shows why it is so important it is to hydrolyze the GTP to inactivate itself

18
Q

Pathway for inositol triphosphate and diacylglyceral signaling

A

G q protein and associated hormone (epinephrine) receptor activation leads to phospholipase C activation which cleaves PIP2 (membrane phospholipid)-> DAG and IP3
IP3: binds ER receptor activating ER localized Ca2+ channels to release Ca2+ to cytosol
DAG: remains in membrane, activates protein kinase C.

19
Q

What does protein kinase C do?

Special feature?

What activates protein kinase C?

A

Phosphorylates proteins/enzymes

It is cAMP independent

Calcium and DAG

20
Q

Calcium is a signaling molecule in what organ?

What is calmodulin?

A

The liver

A common calcium binding protein; has the ability to interact with enzymes (many proteins have calmodulin domains that bind calcium)

21
Q

Path of calcium signaling?

A

Calcium is released from ER stores, 4 calcium binds calmodulin, calmodulin-calcium complex results in conformational change that allows interactions/activation of enzymes involved in metabolism

22
Q

Give an example of when calcium signaling is used in the liver

A

Activation of glycogen degradation in the liver in response to epinephrine binding to alpha 1-adrenergic receptors

23
Q

Combined activity of what 2 things can generate a rapid change in cell activity especially changes in metabolism?

A

Calcium and protein kinase C

24
Q

What 4 organs play a role in fuel metabolism?

Coordination of energy metabolism is controlled by?

A

Liver, brain, adipose and muscle

Primary is insulin and glucagon (peptide hormones) and supporting is epinephrine and norepinephrine (catecholamines)

25
Q

Insulin:

  1. What kind of hormone?
  2. Where is it produced?
  3. Where is it stored?
  4. Promotes the production of what 3 things?
  5. What kind of effector is it?
A
  1. Peptide
  2. Beta cells of the islets of langerhans in the pancreas
  3. Secretory granules
  4. Glycogen, triacylglycerol, and protein
  5. Anabolic effector (makes the answer to number 4 when in the well fed state)
26
Q
  1. What is a C peptide?

2. Clinical relevance?

A
  1. When insulin release happens, it also releases a C peptide in equal amounts
  2. It has a longer half life in the blood so it can tell you how much insulin has been released
27
Q
  1. Beta cell secretion of insulin is coordinated with?

2. Beta cells secrete insulin in response to what three stimuli?

A
  1. Alpha cell secretion of glucagon

2. Glucose, amino acids, and GI hormones

28
Q
  1. Increase in blood glucose will lead to a ___ insulin release
  2. Increase in blood concentration of amino acids will lead to ___ insulin release; what also happens?
A
  1. Increase

2. Increase; glucagon release is immediately upregulated to compensate for increased insulin and thus glucose uptake

29
Q

Function of the gastrointestinal hormones in relation of insulin secretion?

A

Peptide hormones are released from the small intestine as “anticipatory insulin release stimulators” in response to food ingestion (mechanistic release of insulin, not related to high carb meals)

30
Q

Two things that would negatively affect insulin secretion ? (Inhibit)

A

Scarcity of dietary fuel (glucose/amino acids) and increase in blood levels of epinephrine (epinephrine increases mobilization of glucose from the liver and mobilization of fatty acids from adipose)

31
Q
  1. Epinephrine is released by?

2. It is released in response to?

A

Adrenal medulla

Stress, trauma, extreme exercise

~ can override the norma glucose stimulated release of insulin

32
Q

Insulin is secreted in the blood flowing toward ?

A

The liver

33
Q

4 steps of insulin signaling?

A
  1. Insulin binds and activates insulin receptors tyrosine kinase
  2. Insulin receptor auto-phosphorylates its beta subunit’s tyrosine residues
  3. Activated insulin receptor (tyrosine kinase) phosphorylates Insulin Receptor Substrates (IRS -> IRS-P)
  4. IRS-P activate a number of proteins that affect gene expression, cell metabolism, and cell growth
34
Q

Insulin promotes the recruitment of GLUT4 to where?

So once insulin is detected and IRSs are phosphorylated, what happens?

A

Plasma membranes in skeletal muscle and adipose tissue
(GLUT4 is associated with membranes on the cell called endosomes which are just vesicles fused together)

IRSs drive these vesicles that house GLUT4 to the cell surface to drive glucose into the cell until the insulin signal goes away

35
Q
  1. Name two tissues that have glucose transporters that are insulin sensitive and what kind of transport they require
  2. Name 3 parts of body that are NOT insulin sensitive that use active transport
  3. Name 6 parts of body that are NOT insulin sensitive that use facilitated transport
A
  1. Skeletal muscle and adipose tissue; facilitated transport (passive)
  2. Epithelia of intestine, renal tubules, and choroid plexus
  3. Erythrocytes, leukocytes, lens of eye, cornea, liver and brain
36
Q

Glucagon

  1. What kind of hormone?
  2. Where is it produced?
  3. What kind of effector?
  4. What does it do?
  5. Activates?
A
  1. Peptide
  2. Alpha cells of islets of langerhans in the pancreas
  3. Catabolic
  4. Produces and releases glucose from liver
  5. Maintains blood glucose levels by activating gluconeogenesis and glycogenolysis
37
Q
  1. Glucagon secretion is stimulated by increasing __ and __ levels
  2. Inhibited by increasing __ and __ levels
A
  1. Amino acids and epinephrine (when amino acids are in the blood it will trigger small release of both glucagon and insulin)
  2. Insulin and glucose
38
Q

Glucagon is secreted in the blood flowing ___

A

Toward the liver

39
Q

Glucagon signaling pathway (4 steps)

A
  1. Glucagon binds to receptor and indirectly activates adenylyl cyclase (via G protein)
  2. Adenylyl cyclase generates cAMP
  3. CAMP promotes activation of protein kinase
  4. Protein kinase phosphorylates and activates metabolic enzymes
40
Q

Name 3 effects of glucagon signaling

A
  1. Immediate rise in blood glucose (due to increased breakdown of liver glycogen and increased gluconeogenesis
  2. Activates lipolysis in adipose (FFA are used by liver to generate acetyl coenzyme A which is used in ketogenesis)
  3. Amino acid uptake by the liver (used to generate carbon skeletons used in gluconeogenesis)

Biochemistry Block 2 (12 decks)

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