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BIOCHEMISTRY > EXAM3_L29_Metabolic_Signaling > Flashcards

EXAM3_L29_Metabolic_Signaling Flashcards

1
Q

How does Glucagon signaling work/increase PKA activity?

A

GalphaS GPCR increases cAMP-> Increases PKA activity

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2
Q

What two ways does insulin decrease PKA activity?

A
  1. protein phosphatase-1 (dephosphorylates PKA substrates)

2. insulin-responsive cAMP phosphodiesterase (less cAMP, less PKA)

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3
Q

What does insulin and glucagon do to PKA activity respectively?

A

Insulin- decreases PKA (two ways)

Glucagon- increases cAMP thus PKA activity

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4
Q

Insulin signaling via IRS1- Two events when insulin binds RTK:

A

UPON INSULIN SIGNAL: (insulin binds RTK):

  1. IRS1 binds GRB2 > MAPK (cell division, survival)
  2. IRS1 bind PI3K> AKT (increase glucose uptake GLUT4)

akt-also alters metabolic enzyme activities

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5
Q

What is the assumption of a defective IRS-1 signaling pathway?

A
  • Consequence of obesity

- can result in insulin resistance and diabetes

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6
Q

What is the newly phosphorylated domain of IRS-1?

what two things bind to this domain?

A
  • SH2 domain (src homology 2)
  • can bind to : GRB2 or PI3K

GRB2 >SOS> MAPK pathways
PI3K (pi3 kinase)>activates AKT pathway

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7
Q

What are the 4 counterregulatory Hormones?

What do they do?

A

Oppose action of insulin by mobilizing fuels into blood

  • Glucagon
  • Cortisol
  • Epinephrine
  • Norepinephrine
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8
Q

What hormones are stress released in response to neuronal signals?

What is the signal pathway for these from the brain?

A

Cortisol (adrenal cortex)
Epinephrine (adrenal medulla)
Norepinephrine (adrenal medulla)

Hypothalamus>Pituitary>ACTH>Adrenal Gland

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9
Q

When you exercise, or experience HYPOGLYCEMIA, hypoxia, or hemorrhage what neurotransmitter will be released? What affects will it have on IG ratio?

A

Epinephrine- catecholamine (from tyrosine)

  • Decreases IG ratio
  • increases and mobilizes fuel/energy into blood
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10
Q

Cortisol is a glucocorticoid derived from Cholesterol (adrenal cortex) - why is that significant?

A

Cortisol binds receptors INSIDE THE CELL

-steroid diffuses right through plasma membrane

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11
Q

Cortisol functions differently in Adipose, Muscle, and Liver

What does it do in each?

A

Adipose- lipolysis (provides energy for liver gluconeogenesis)

Muscle- Decreases GLUT4 uptake of glucose

Liver- Gluconeogenesis (increase glucose production)

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12
Q

Why do Dietary Amino Acids stimulate Insulin High glucose and low glucose states?

A

High glucose state- AA’s convert to glucose> insulin

Low glucose state- AA’s from high protein diet can be made into glucose and stimulate a little insulin to prevent muscle breakdown

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13
Q

Is fat ever used to make glucose?

A

NOPE

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14
Q

What affects of glucagon in muscle, liver, adipose?

A

LIVER ONLY (only gasGPCR receptors on Liver Cells)

  • mobilizes nutrient molecules,
  • glycogenolysis (glycogen breakdown for export)
  • gluconeogenesis for export (using AA’s as C source not FA’s)
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15
Q

Glucagon receptors are only found on Liver cells
(for liver glycogen breakdown) and will not affect the stored glycogen in muscle cells.

How is Muscle glycogen used then?

A

Epinephrine stimulates glycogenolysis of muscle glycogen to be used ONLY FOR THE MUSCLE ITSELF

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16
Q

What is muscle glycogen used for?

A

Only used for its own glycogenolysis>glucose

NEVER USED FOR BLOOD GLUCOSE HOMEOSTASIS!

17
Q

How does epinephrine affect Muscle, Adipose, Liver, Pancreas?

A

Muscle- glycogenolysis (glycogen>glucose) MUSCLE USE

Liver- glycogenolysis (glycogen>glucose) for EXPORT

Adipose- FA’s mobile for use

Pancreas- Increases alpha cell (glucagon secretion)
inhibits beta cell (insulin secretion)

18
Q

What does the liver use for energy?

What does it never use?

A

Beta oxidation of FAT

NEVER USES GLYCOGEN (exported to brain & RBCs)

19
Q

How are blood glucose levels maintained when fasting?

A

Gluconeogenesis (from aa’s to glucose)

Glycogenolysis (glycogen to glucose) while supplies last

20
Q

Stress or Low IG ratio in Liver?

A

glucagon and Epinephrine:

  • gluconeogenesis
  • glycogenolysis
  • ketone bodies
21
Q

High IG ratio in Liver?

A

Insulin:
glycogenesis
lipogenesis

22
Q

Where are ketone bodies only made?

A

KB Made in Liver (can’t be used in liver) Used by other cells only

23
Q

High IG ratio in Adipose?

A

Insulin:
LIPOGENESIS
Glucose Uptake (GLUT4)

FFA synthesis in liver stored TAGs in adipose
-(glucose>glycerol)

24
Q

When will Lipolysis occur in adipose tissue?

A

ONLY EPINEPHRINE (stress only)

-TAGs of adipose mobilized into FFA’s in circulation

Stress( HYPOGLYCEMIA, Hypoxia, exercise, Hemorrhage, pain)

25
Q

Low IG ratio in adipose?

A

No affect! -
- NO GLUCAGON RECEPTORS
- only has epinephrine receptors
(lipolysis will only occur during stress/epinephrine signaled

26
Q

High IG ratio in muscle?

A

Insulin:
-AMPK> GLUT4 glucose uptake

-Glycogenesis* (store glucose as glycogen)

  • this glycogen can only be used in the muscle
  • only used when epinephrine/stress induced

note: AMPK glucose is metabolized, and not stored

27
Q

How much glucose goes to the muscles after a meal?

A

80%

28
Q

Low IG ratio in muscle?

A

NO EFFECT!
- no glucagon receptors on muscles (only has epi receptor)

-glycogenolysis occurs via epinephrine/stress only!

29
Q

What is important about glucose that enters the muscle as AMPK?

A

It is metabolized and not stored as glycogen!

30
Q

Stress to muscle cells?

exercise, hemorrhage, HYPOGLYCEMIA, Hypoxia, Pain)

A

Epinephrine

31
Q

Insulin stimulates glucose uptake in the muscles via GLUT4.

When insulin is low or signal impaired, GLUT4 can still be stimulated by what pathway?

A

AMPK (activated protein kinase) pathway

32
Q

small rise in AMP has what effect compared to ATP?

A

an AMP increase has much bigger increase in activity than equivalent amount of ATP increase

33
Q

What does Adenylate Kinase do?

A

takes 2 ADPs and makes an ATP

34
Q

AMP increases AMPK by what two ways?

A
  1. Allosteric activates AMPK (5x greater activity)

2. Stim phosphorylation of AMPK (100x greater activity)

35
Q

What is Metformin?

A

Most common Type II Diabetes medication

  • Allows GLUT4 to uptake glucose in the muscles
  • increases AMP and> AMPK activation
  • AMPK benefits independent of insulin signaling
36
Q

What are the benefits of metformin on blood glucose levels?

A
  • increases uptake of glucose in the muscle (GLUT4)
  • stops gluconeogenesis in liver

*Independent of insulin signaling

37
Q

What are the benefits of metformin on blood lipid levels?

A

promotes beta oxidation rather than storage

  • Reduces TAGS in circulation
  • improves insulin sensitivity

BIOCHEMISTRY (33 decks)

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