Week 4 Integration of Metabolic Pathways Lecture

Question 1

Can ATP produced in the liver be used in the kidney?

Answer 1

NO. ATP is not transported between cells

Question 2

PFK-1 role:

Answer 2

converts Fructose-6-phosphate to Fructose-1,6-BP (in glycolysis)

Question 3

how is PFK-1 regulated?

Answer 3

Allosterically. promoted by AMP or F-2,6-BP. Inhibited by ATP and citrate.

Question 4

what are examples of catecholamines? where are they produced?

Answer 4

E/NE, adrenal gland

Question 5

describe E/NE in the liver

Answer 5

1. E/NE binds GPCR on membrane
2. GPCR activates Gs, and G-alpha and G-beta/gamma dissociate
3. G-alpha activates adenyl cyclase which produces cAMP.
4. cAMP activates PKA
5. PKA phosphorylates and activates phosphorylase kinase
6. phosphorylase kinase converts inactive glycogen phosphorylase b to active glycogen phosphorylase a
7. PKA inactivates glycogen synthase
8. glycogen ins broken down

Question 6

what are the effects of catecholamines on skeletal muscle (4)

Answer 6

1. increase glycolysis
2. decrease glycogen synthesis
3. increase glycogenolysis (degrade glycogen)
4. increase triglyceride utilization

Question 7

what are the effects of catecholamines on liver (5)?

Answer 7

1. decrease glycolysis
2. increase glycogen breakdown
3. decrease glycogen synthesis
4. increase gluconeogenesis
5. decrease FA synthesis

Question 8

what are the effects of catecholamines on adipose tissue? 2

Answer 8

1. increase lipolysis (release FFAs, HSL)

2, decrease triglyceride utilization

Question 9

what explains the differing role in skeletal muscle and liver in response to catecholamines?

Answer 9

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)

Question 10

Glucocorticoids are produced when?

Answer 10

during chronic stress

Question 11

what is the overall role of glucocorticoids, how does this compare to catecholamines?

Answer 11

GCs: regulate gene expression and are therefore much slower acting than catecholamines which are immediate fight/flight

Question 12

how does adipose tissue respond to increased glucocorticoids? 2

Answer 12

increased lipolysis, increased expression of lipases

Question 13

how does skeletal muscle respond to an increase in glucocorticoids? why/how?

Answer 13

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

Question 14

how does the liver respond to increased glucocorticoids?2

Answer 14

increase gluconeogenesis, increase glycogen synthesis

Question 15

cortisol is an example of a ….

Answer 15

glucocorticoid

Question 16

increased chronic stress (increased cortisol) can be thought of as_____ and increased catecholamines can be though of as_____

Answer 16

cortisol: storing energy to prepare for an attack
Catecholamine: using the stored energy

Question 17

how is alcohol absorbed in our bodies

Answer 17

via simple diffusion in SI and stomach

Question 18

how is alcohol distributed in our bodies?

Answer 18

alcohol is lipid (small polar) and water soluble (polar) so it can cross membranes and distribute in water-filled environments (except in adipose)

Question 19

where is alcohol metabolized?

Answer 19

liver

Question 20

what two systems are used to metabolize alcohol? where within liver cells are these processes located

Answer 20

Alcohol dehydrogenase system (cytoplasm of liver cells), microsomal ethanol oxidizing system (MEOS, ER of liver)

Question 21

when do we see the microsomal ethanol oxidizing system? what does it require

Answer 21

induced by heavy drinking. NADPH required

Question 22

What is the main product of alcohol metabolism?

Answer 22

Acetyl-CoA

Question 23

the metabolism of ethanol produces an abundance of…

Answer 23

NADH

Question 24

what issues arise as a result of the increased NADH/NAD+ ratio during alcohol consumption.

Answer 24

An abundance of aceyl-CoA, NADH and ATP causes:

1. glucose metabolism stops (no need for energy, regulated at PFK-1 and PDH)
2. Hyperlidemia: decrease in FA breakdown (no need for energy, decreased NAD) and increased FA storage (TGs) which increase VLDL
3. Hypoglycemia: A decrease in gluconeogenesis due to the formation of lactate (high NADH/NAD) being favored over the formation of glucose from pyruvate/oxaloacetate

Question 25

what is resveratrol?

Answer 25

cmpd in wine that has shown to extend life in some organsims but not humans

Question 26

what three molecules are key junctions in metabolism?

Answer 26

G6P, pyruvate, acetyl-CoA

Question 27

GPP can follow what three pathways?

Answer 27

Pentose phosphate pathway (NADPH, nucleotides), Glycolysis/TCA (pruvate formation), Glycogen formation (G1P)

Question 28

Pyruvate can be converted to what molecules?4

Answer 28

Oxaloacetate (can feed into gluconeogenesis), Lactate, Alanine, Acetyl-CoA