Protein turnover and amino acid catabolism

Question 1

What is the proteasome?

Answer 1

Barrel like protein structure–proteins to be degraded are inserted

Protease activity inside

Lids have ATPase activity and can unfold substrates and deliver into barrel

Question 2

What is a lysosome?

Answer 2

Membrane bound organelle with acid hydrolases inside

Can degrade stuff

Question 3

How are proteins to be degraded identified?

Answer 3

Tagged with ubiquitin–directs proteins to proteasome

Question 4

How are short lived proteins degraded?

Answer 4

By ubiquitin proteasomal system (UPS)

Question 5

What are degrons?

Answer 5

Signals on some short lived proteins that signal for ubiquitination

e.g. N-terminal residues that are basic or bulky hydrophobic residues
or specific peptide sequences

Question 6

How does ubiquitination work?

Answer 6

Catalyed by 3 sequential enzymes–E1, E2, and E3 ligases

Question 7

What does E1 ligase do?

Answer 7

Activates ubiquitin

Covalently binding E1 via high energy thioester bond

Only 1 E1 enzyme

Question 8

What does E2 do?

Answer 8

Covalent bond broken and formed

Dozens of E2 enzymes in body

Question 9

What does E3 do?

Answer 9

Recognizes degrons and binds to them and E2s

Ubiquitin is transfered from E2 to protein substrate

Ubiquiting becomes covalently attached to ubiquitin forming polyubiquitin chain

Question 10

What is the autophagy lysosomal system?

Answer 10

Cellular degradation pathway for long lived proteins and damaged organelles

Question 11

What is chaperone mediated autophagy?

Answer 11

Chaperone proteins bind to target proteins and escort them to the lysosome

Question 12

What is microautophagy?

Answer 12

Small pieces of cytoplasm are engulfed by lysosome and degraded

Question 13

What is macroautophagy?

Answer 13

Large pieces of cytoplasm and organelles become surrounded by a double membrane–isolation membrane–

fuse with a lysosome and degraded.

Question 14

What is a glucogenic amino acid?

Answer 14

Degraded to pyruvate or citric acid cycle intermediates–can be used for gluconeogenesis

Question 15

What is a ketogenic amino acid?

Answer 15

Degraded to acetyl-CoA or acetoacetyl-CoA–can be converted to fatty acids or ketone bodies

Question 16

How does deamination work?

Answer 16

Transamination or oxidative deamination

Excess AAs usually results in synthesis of urea–in liver

Question 17

How is nitrogen transported to liver from muscle?

Answer 17

Amino acid converted to alanine

Alanine transported in blood to liver

Question 18

How is nitrogen transported to liver from non-muscle tissues?

Catalyzed by glutamate dehydrogenase–reverse of the nitrogen fixing reaction that occurs in prokaryotes

Answer 18

Glutamine

Question 19

How is urea synthesized in liver?

Answer 19

Alanine from muscle is converted to glutamate

Glutamine is converted to glutamate and NH4+ by glutaminase

glutamate is converted to NH4+ and alpha-ketoglutarate by glutamate dehydrogenase

NH4+ used to synthesize urea

Question 20

Where do the nitrogens in urea come from?

Answer 20

Ammonium and aspartate

Question 21

How is urea formed?

Answer 21

Carbamoyl phosphate formed in mitochondria by carbamoyl phosphate I

Reacts with ornithine to produce citrulline–enters cytoplasm

Aspartate reacts with citrulline

Cleaved to form fumarate and arginine

Arginase cleaves arginine to form ornithine and urea

Question 22

What is hyperammonemia?

Answer 22

Potentially fatal–high blood levels of NH4+

Question 23

How is urea cycle regulated?

Answer 23

Carbamoyl phosphate synthetase I is allosterically activated when glutamate and arginine levels are high

Question 24

What is the relationship between CAC and urea cycle?

Answer 24

Oxaloacetate can be converted to aspartate which can be used in urea cycle

Fumarate produced in urea cycle enters CAC

Question 25

What is PKU?

Answer 25

Phenylketonuria–accumulate phenylalanine and block AA transport

Brain damage due to low protein and neurotransmitters

Question 26

How does albinism happen?

Answer 26

Deficit in enzymes that convert tyrosine to melanin

Question 27

What is alkpatonuria?

Answer 27

Deficit in enzyme that converts tyrosine to acetoacetate–intermediate accumulates

blackens urine, arthritis risk, alters skin pigmentation

Question 28

What is maple syrup urine disease?

Answer 28

Defect in enzyme that degrades keto acids to propionyl-CoA

accumulates keto-acids

vomiting, convulsions, brain damage

control by limiting branched chain AA consumption