Chapter 31: Integration of Metabolism

Question 1

What secretes corticotropin releasing hormone (CRF)? Where does it bind?

Answer 1

Released by Hypothalamus, binds to anterior pituitary gland

Question 2

What does CRF stimulate the anterior pituitary to release? What does it target?

Answer 2

releases adrenocorticotropic hormone (ACTH), targets the adrenal cortex

Question 3

What does ACTH stimulate the adrenal cortex to release? What does it target?

Answer 3

releases cortisol, binds to targets tissues like the liver, muscle and adipose tissue

Question 4

What does cortisol inhibit?

Answer 4

High levels of cortisol (from adrenal cortex) inhibits the hypothalamus —> stops release of CRF and its downstream effects

**NEGATIVE FEEDBACK

Question 5

Layers of adrenal gland and types of secretion?

Answer 5

1. zona glomerulosa (adrenal cortex): Mineralocorticoids aka “salt” (aldosterone)
2. zona fasciculata (adrenal cortex): glucocorticoids aka “sugar” (cortisol)
3. zona reticularis (adrenal cortex): androgens aka sex hormones (Dehydroepiandrosterone (DHEA) and androstenedione)

“the deeper you go, the sweeter it gets”

4. adrenal medulla (deepest): catecholamines (Dopamine, epinephrine, norepinephrine)

Question 6

What steroid hormone stimulates gluconeogenesis, protein degradation in muscle, mobilization of fatty acids from adipose tissue?

Answer 6

CORTISOL (“stress hormone”)

Question 7

What occurs FIRST when a stress hormone (epi, NE, glucagon) binds to a GCPR?

Answer 7

stimulates the binding of GTP (instead of GDP) to the alpha subunit of the G-protein —> activates the G-protein

Question 8

Once a Gq protein (alpha adrenergic) is activate (GTP + alpha subunit), what does it activate next?

Answer 8

It activates Phospholipase C —> PLC cleaves PIP2 into IP3 and DAG (2nd messengers)

Question 9

Roles of IP3 and DAG (2nd messengers of activated Gq)?

Answer 9

IP3: binds to ER and causes an influx of calcium

DAG: uses Ca2+ to activate protein kinase C. PKC then phosphorylates stuff downstream

Question 10

Once a Gs protein (beta adrenergic) is activate (GTP + alpha subunit), what does it activate next?

Answer 10

It activates adenylyl cyclase —> AC then converts ATP —> cAMP (2nd messenger)

Question 11

Role of cAMP (2nd messenger of Gs)?

Answer 11

4 cAMPs can unbind and activate (free) protein kinase A —> active PKA phosphorylates things downstream l

Question 12

What GCPR receptors are found ONLY in liver and are Gs? What is their effect once activated?

Answer 12

glucagon receptors!!!

Once PKA is activated by 4 cAMPs (active Gs —> active AC —> activate cAMP), it phosphorylates lipase

Lipase breakdowns triglycerides —> FAs (mobile) for beta-oxidation

Question 13

what secretes glucagon?

Answer 13

alpha cells of the pancreas

Question 14

what secretes insulin (ANABOLIC hormone)?

Answer 14

beta cells of pancreas

Question 15

What stimulates insulin secretion?

Answer 15

Increased ATP due to increased glucose

Question 16

During insulin secretion, what does an increased ATP/ADP ratio cause? What is the end result?

Answer 16

It closes K+ channels (stops K+ from leaving) = depolarization

Once depolarized, voltage gated Ca2+ channels. Intracellular Ca2+ causes insulin gene expression and secretion (exocytosis)

Question 17

Metabolism pathways of the liver

Answer 17

Question 18

Alcohol metabolism substrates and products?

Answer 18

substrate: ethanol
products: acetyl CoA, NADH

Question 19

What does disulfiram inhibit in alcohol metabolism? Effect?

Answer 19

Inhibits: aldehyde dehydrogenase (acetaldehyde —> acetate)

effect: increased acetaldehyde —> worsens your hangover

**used to treat alcoholism bc it worsens the side-effects of alcohol

Question 20

substrates and products of ketone body synthesis?

Answer 20

substrate: 2 molecules of acetyl CoA
products (2 different pathways):
1. acetoacetate —> acetone (spontaneous)
2. acetoacetate + NADH <—> beta-hydroxy butyrate + NAD+ via dehydrogenase (reversible)

Question 21

Where does ketone body synthesis occur?

Answer 21

MITOCHONDRIAL MATRIX OF THE LIVER

Question 22

Where does Ketogenolysis occur? What are the substrates and products?

Answer 22

Location: Liver, extrahepatic tissues (brain, muscle, renal cortex)

Substrate: acetoacetate (from HMG CoA or hydroxybutyrate)

Products: 2 acetyl CoA (used in TCA cycle to make energy)

Question 23

What key enzyme in ketogenolysis is ONLY expressed in ketone body utilizing tissues (liver, extrahepatic)?

Answer 23

THIOPHORASE

Question 24

Adipose tissues store fat in the form of _____?

Answer 24

triglycerides (triacylglycerol)

Question 25

Brain metabolism under normal vs extreme conditions?

Answer 25

normal: glucose metabolism (glycolysis): does NOT use FAs for energy

extreme conditions (ex: starvation): ketone bodies (ketogenolysis)

Question 26

Muscle metabolism under normal vs extreme conditions?

Answer 26

normal: glycogen synthesis/degradation, lipid degradation

extreme: protein degradation (AA’s for energy), ketone bodies