Week 4 Integration of Metabolic Pathways Lecture Flashcards
Can ATP produced in the liver be used in the kidney?
NO. ATP is not transported between cells
PFK-1 role:
converts Fructose-6-phosphate to Fructose-1,6-BP (in glycolysis)
how is PFK-1 regulated?
Allosterically. promoted by AMP or F-2,6-BP. Inhibited by ATP and citrate.
what are examples of catecholamines? where are they produced?
E/NE, adrenal gland
describe E/NE in the liver
- E/NE binds GPCR on membrane
- GPCR activates Gs, and G-alpha and G-beta/gamma dissociate
- G-alpha activates adenyl cyclase which produces cAMP.
- cAMP activates PKA
- PKA phosphorylates and activates phosphorylase kinase
- phosphorylase kinase converts inactive glycogen phosphorylase b to active glycogen phosphorylase a
- PKA inactivates glycogen synthase
- glycogen ins broken down
what are the effects of catecholamines on skeletal muscle (4)
- increase glycolysis
- decrease glycogen synthesis
- increase glycogenolysis (degrade glycogen)
- increase triglyceride utilization
what are the effects of catecholamines on liver (5)?
- decrease glycolysis
- increase glycogen breakdown
- decrease glycogen synthesis
- increase gluconeogenesis
- decrease FA synthesis
what are the effects of catecholamines on adipose tissue? 2
- increase lipolysis (release FFAs, HSL)
2, decrease triglyceride utilization
what explains the differing role in skeletal muscle and liver in response to catecholamines?
both cells have PFK-1 that is promoted by F-2,6-BP. However, the enzyme that produces F-2,6-BP are different in each cell type (isozymes) even though they are both phosphorylated by cAMP-PKA signaling. In the liver, phosphorylation of F-2,6-BPase deactivates the enzyme (less F-2,6-BP, no glycolysis) and in the skeletal muscle phosphorylation of F-2,6-BPase activates the enzyme (more F-2,6-BP and more glycolysis)
Glucocorticoids are produced when?
during chronic stress
what is the overall role of glucocorticoids, how does this compare to catecholamines?
GCs: regulate gene expression and are therefore much slower acting than catecholamines which are immediate fight/flight
how does adipose tissue respond to increased glucocorticoids? 2
increased lipolysis, increased expression of lipases
how does skeletal muscle respond to an increase in glucocorticoids? why/how?
increase protein degradation in peripheral tissues (smaller muscles) due to increased expression of protease enzymes. these non-essential muscles are used to make AA that produce energy
how does the liver respond to increased glucocorticoids?2
increase gluconeogenesis, increase glycogen synthesis
cortisol is an example of a ….
glucocorticoid
increased chronic stress (increased cortisol) can be thought of as_____ and increased catecholamines can be though of as_____
cortisol: storing energy to prepare for an attack
Catecholamine: using the stored energy
how is alcohol absorbed in our bodies
via simple diffusion in SI and stomach
how is alcohol distributed in our bodies?
alcohol is lipid (small polar) and water soluble (polar) so it can cross membranes and distribute in water-filled environments (except in adipose)
where is alcohol metabolized?
liver
what two systems are used to metabolize alcohol? where within liver cells are these processes located
Alcohol dehydrogenase system (cytoplasm of liver cells), microsomal ethanol oxidizing system (MEOS, ER of liver)
when do we see the microsomal ethanol oxidizing system? what does it require
induced by heavy drinking. NADPH required
What is the main product of alcohol metabolism?
Acetyl-CoA
the metabolism of ethanol produces an abundance of…
NADH
what issues arise as a result of the increased NADH/NAD+ ratio during alcohol consumption.
An abundance of aceyl-CoA, NADH and ATP causes:
- glucose metabolism stops (no need for energy, regulated at PFK-1 and PDH)
- Hyperlidemia: decrease in FA breakdown (no need for energy, decreased NAD) and increased FA storage (TGs) which increase VLDL
- Hypoglycemia: A decrease in gluconeogenesis due to the formation of lactate (high NADH/NAD) being favored over the formation of glucose from pyruvate/oxaloacetate
what is resveratrol?
cmpd in wine that has shown to extend life in some organsims but not humans
what three molecules are key junctions in metabolism?
G6P, pyruvate, acetyl-CoA
GPP can follow what three pathways?
Pentose phosphate pathway (NADPH, nucleotides), Glycolysis/TCA (pruvate formation), Glycogen formation (G1P)
Pyruvate can be converted to what molecules?4
Oxaloacetate (can feed into gluconeogenesis), Lactate, Alanine, Acetyl-CoA
