Chapter 31: Integration of Metabolism Flashcards
What secretes corticotropin releasing hormone (CRF)? Where does it bind?
Released by Hypothalamus, binds to anterior pituitary gland
What does CRF stimulate the anterior pituitary to release? What does it target?
releases adrenocorticotropic hormone (ACTH), targets the adrenal cortex
What does ACTH stimulate the adrenal cortex to release? What does it target?
releases cortisol, binds to targets tissues like the liver, muscle and adipose tissue
What does cortisol inhibit?
High levels of cortisol (from adrenal cortex) inhibits the hypothalamus —> stops release of CRF and its downstream effects
**NEGATIVE FEEDBACK
Layers of adrenal gland and types of secretion?
- zona glomerulosa (adrenal cortex): Mineralocorticoids aka “salt” (aldosterone)
- zona fasciculata (adrenal cortex): glucocorticoids aka “sugar” (cortisol)
- zona reticularis (adrenal cortex): androgens aka sex hormones (Dehydroepiandrosterone (DHEA) and androstenedione)
“the deeper you go, the sweeter it gets”
- adrenal medulla (deepest): catecholamines (Dopamine, epinephrine, norepinephrine)
What steroid hormone stimulates gluconeogenesis, protein degradation in muscle, mobilization of fatty acids from adipose tissue?
CORTISOL (“stress hormone”)
What occurs FIRST when a stress hormone (epi, NE, glucagon) binds to a GCPR?
stimulates the binding of GTP (instead of GDP) to the alpha subunit of the G-protein —> activates the G-protein
Once a Gq protein (alpha adrenergic) is activate (GTP + alpha subunit), what does it activate next?
It activates Phospholipase C —> PLC cleaves PIP2 into IP3 and DAG (2nd messengers)
Roles of IP3 and DAG (2nd messengers of activated Gq)?
IP3: binds to ER and causes an influx of calcium
DAG: uses Ca2+ to activate protein kinase C. PKC then phosphorylates stuff downstream
Once a Gs protein (beta adrenergic) is activate (GTP + alpha subunit), what does it activate next?
It activates adenylyl cyclase —> AC then converts ATP —> cAMP (2nd messenger)
Role of cAMP (2nd messenger of Gs)?
4 cAMPs can unbind and activate (free) protein kinase A —> active PKA phosphorylates things downstream l
What GCPR receptors are found ONLY in liver and are Gs? What is their effect once activated?
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
what secretes glucagon?
alpha cells of the pancreas
what secretes insulin (ANABOLIC hormone)?
beta cells of pancreas
What stimulates insulin secretion?
Increased ATP due to increased glucose
During insulin secretion, what does an increased ATP/ADP ratio cause? What is the end result?
It closes K+ channels (stops K+ from leaving) = depolarization
Once depolarized, voltage gated Ca2+ channels. Intracellular Ca2+ causes insulin gene expression and secretion (exocytosis)
Metabolism pathways of the liver
Alcohol metabolism substrates and products?
substrate: ethanol
products: acetyl CoA, NADH
What does disulfiram inhibit in alcohol metabolism? Effect?
Inhibits: aldehyde dehydrogenase (acetaldehyde —> acetate)
effect: increased acetaldehyde —> worsens your hangover
**used to treat alcoholism bc it worsens the side-effects of alcohol
substrates and products of ketone body synthesis?
substrate: 2 molecules of acetyl CoA
products (2 different pathways):
1. acetoacetate —> acetone (spontaneous)
2. acetoacetate + NADH <—> beta-hydroxy butyrate + NAD+ via dehydrogenase (reversible)
Where does ketone body synthesis occur?
MITOCHONDRIAL MATRIX OF THE LIVER
Where does Ketogenolysis occur? What are the substrates and products?
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)
What key enzyme in ketogenolysis is ONLY expressed in ketone body utilizing tissues (liver, extrahepatic)?
THIOPHORASE
Adipose tissues store fat in the form of _____?
triglycerides (triacylglycerol)
Brain metabolism under normal vs extreme conditions?
normal: glucose metabolism (glycolysis): does NOT use FAs for energy
extreme conditions (ex: starvation): ketone bodies (ketogenolysis)
Muscle metabolism under normal vs extreme conditions?
normal: glycogen synthesis/degradation, lipid degradation
extreme: protein degradation (AA’s for energy), ketone bodies
