lecture 5: amino acid metabolism 1

Question 1

why don’t amino acids have a storage form?

Answer 1

we can convert protein to ATP, still being used

Question 2

protein turnover

Answer 2

synthesis and degradation of protein
influenced by factors such as oxidation

Question 3

free amino acid pool remains constant

Answer 3

process that remove AAs = those that add amino acids
S + E = D + I
Positive nitrogen balance S > D
neg S < D
occur at equal rates S = D

Question 3

how is excess nitrogen removed from the body?

Answer 3

AA breakdown removes nitrogen from body in the form of ammonia or urea
carbon skeletons remaining from removed N can enter TCA cycle

Question 4

why would a protein turnover be required, even when the body requires no net gain or loss of protein?

Answer 4

replace proteins that have been oxidized, damaged, misfolded
adapt to new physiological and nutritional conditions (muscle breakdown - fasting state, starvation, illness)

Question 5

which organs have higher protein turnover?

Answer 5

stomach, esophagus, colon - GI tract, replace epithelial lining
liver - metabolism

Question 6

what individual proteins have higher turnover rates?

Answer 6

regulatory proteins - rapid adaptation of changing conditions

Question 7

insulin in protein regulation

Answer 7

stimulates protein synthesis, inhibits protein degredation

insulin levels increase with feeding and decrease during fasting

signaling cascade > activation of mRNA translation

Question 8

insulin protein synthesis activation mechanism

Answer 8

insulin or IGF-1 binds to receptor to stimulate Tyr phosphorylation of IRS-1

IRS-1 activation > stimulates kinases PI3K and pAKT

pAKT inactivates FoxO, which promotes protein breakdown, via phosphorylation > FoxO cannot enter nucleus

pAKT activates mTOR (promotes protein synthesis)

Question 9

IRS-1

Answer 9

signaling adapter protein that plays a role in transmitting the signal from insulin to various kinases

activation > stimulates pAKT/PI3K

Question 10

pAKT

Answer 10

kinase that inactivates FoxO, activates mTOR

Question 11

FoxO

Answer 11

promotes expression of E3 ubiquitin ligases (genes involved in protein degradation), therefore promotes protein breakdown

Question 12

mTOR

Answer 12

promotes protein synthesis

Question 13

growth hormone (GH)

Answer 13

promotes longitudinal growth in adolescents
secreted by pituitary gland
initiates signal transduction that promotes expression of anabolic process genes

Question 14

growth hormone anabolic cascade

Answer 14

GH binds to cell surface receptor, activates JAK2

JAK2 phosphorylates STAT proteins

phos. STAT proteins dimerize and enter nucleus

STAT proteins bind to specific DNA sequences, increasing expression (including IGF-1)

Question 15

transcription factors

Answer 15

FoxO, STAT proteins
influence transcription process of various genes they regulate
enter the nucleus

Question 16

anabolic hormones in protein synthesis

Answer 16

insulin, IGF-1, GH

Question 17

catabolic hormones in protein degradation

Answer 17

glucagon, cortisol, myostatin

Question 18

glucagon

Answer 18

promotes gluconeogenesis from amino acids > not available for protein synthesis (redirection)

Question 19

cortisol

Answer 19

glucocorticoid hormone produced in the adrenal cortex
released in response to low glucose, stimulates gluconeogenesis

decrease protein synthesis and increase degredation

promote FoxO
inhibits eIF4 (initiates eukaryotic translation), therefore inhibiting synthesis

Question 20

myostatin

Answer 20

signaling molecule that inhibits the growth and differentiation of muscle cells, inducer of muscle wasting

inhibits insulin and IGF-1 signaling, mTOR effects

increases FoxO activity

Question 21

cytokines

Answer 21

peptides produced by cells of the immune system
reallocates muscle tissue to immune response

TNFa activates NF-kB > ubiquitin proteasome pathway

Question 22

inhibits protein synthesis

Answer 22

Y4E-BP, myostatin, glucagon, cortisol, TNFa/NF-kB

Question 23

promote protein synthesis

Answer 23

S6 kinase, eIF4 complex, mTOR, insulin, PI3K/pAKT, IRS-1, GH

Question 24

anabolic response to eating

Answer 24

insulin and AA supply > translation mRNA into protein
1) dephosphorylation of EIF2 > formation of pre-initiation complex
2) increased binding of eIF4 to mRNA

Question 25

fasting process

Answer 25

post-absorptive: insulin decreases, glucagon increases
early starvation: glycogen levels spent
long-term starvation: whole body protein degradation rates decrease > adipose depleted > protein degradation begins again

Question 26

exercise in protein synthesis

Answer 26

resistance exercise > mTOR signaling to promote S6 kinase and inhibit 4E-BP
4E-BP binds and inhibits eIF4 > prevents pre-initiation complex
mTOR inhibits 4E-BP
S6 kinase promotes pre-initiation complex