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Flashcards in Protein Degradation Deck (36):
1

Two systems of protein degradation

extracellular
intracellular

2

EC Protein Degradation

diet: proteins --> epithelial cells of SI (absorption)--> liver (by the portal vein for processing): AAs

3

4 steps of protein catabolism

*1) degradation of proteins to AAs
*2) removal of AA group
*3) elimination of ammonia (urea)
4) fate of the carbon chain...

4

Which can be stored?
fat, carb, protein

only fat and carb can be stored (protein/AAs/ammonia cannot be stored)

5

What happens to AAs of protein?

Carbon chain goes for storage but NH3 gets excreted

6

What are 2 roles of trypsin?

cut proteins in diet; cut other proteases (zymogens)

-lacks protein target specificity

7

Why is no ATP required for absoprtion of proteins?

Acidity of gut environment

(In cells, you need ATP to de-fold proteins)

8

Describe the transamination reaction

take nitrogen group from alpha amino acid from diet and add it to glutamate using AMINOTRANSFERASE (multiple)

*converted AA to ketoacid, which is basically a carbon chain

*no energy requirement,
*fully reversible
*no energy needed

9

What is the essential co-factor required for transamination reaction?

pyridoxal phosphate (B6 derivative)

10

What are the 3 important AA/Ketoacid pairs (that feed into TCA)?

1) glutamate alpha-ketoglutarate
2) alanine pyruvate
3) aspartate oxaloacetate

11

What is the role of "glutamate alpha-ketoglutarate" ?

transamination

12

What is the role of alanine pyruvate?

glucose-alanine cycle: capture of ammonia in peripheral tissue and safe transportation of that ammonia to the liver

13

What is the role of aspartate oxaloacetate?

urea cycle (donates second nitrogen into the cycle)

14

Why the tight coupling btwn AA breakdown and TCA?

energy requirement (depletion)

these are the sensors to tell you time to start breaking down protein:
1) glutamate alpha-ketoglutarate
2) alanine pyruvate
3) aspartate oxaloacetate

15

What is arginine's effect on S-ethyglutamate (cofactor for CPS1)?

stimulates as [arg] increases

16

CPS1

rate limiting factor in pathway

17

Why is the urea cycle irreversible?

1) energy requirement
2) compartmentalized

18

How is urea cycle regulated?

-positively regulated:
arg positively regulates cofactor for CPS1 (RLS enzyme)

19

What is the nitrogen source for the urea cycle?

glutamate (directly and indirectly)

20

What is the net effect in step(s) of urea cycle?

hyperammonenemia
(eg: Mutation in CPS1)

21

What is the physiological response to sudden "pulse" of ammonia?

1) attach ammonia to pyruvate and make alanine --> transport to liver --> catalyze hydrolysis there

22

What are key enzymes only expressed in liver?

asparginase, glutaminase, arginase, CPS1

23

Which reactions require: Vitamin B6 (pyridoxal phosphate)?

x

24

Which reactions require: S-adenosyl methionine?

x

25

Which reactions require: tetrahydrobiopterin?

x

26

Which reactions require: folate?

x

27

Which reactions require: Vitamin B12 (methylcobolamin)?

x

28

What is the RLS of the urea cycle?

x
Enzyme: CPS1

29

What is the ALLOSTERIC EFFECTOR of the urea cycle?

X

30

How is energy coupled to nitrogen incorporation in the urea cycle?

x

31

What are the dedicated enzymes of the urea cycle?

LIVER: arginase, asparinginase, glutaminase, CPS1

32

How would a spike in ammonia levels be temporarily controlled?

glutamate --> glutamine

33

Whats the difference btwn glutamate dehydrogenase and aminotransferase?

x

34

What are 3 liver-specific enzymes that are involved in ammonia metabolism?

x

35

What is the effect of mutations in CPS1 and N-acetylglutamate synthase?

x

36

What are 3 reactions that primarily occur in the liver relating to the urea cycle?

glutamine --> glutamate;
asparagine --> aspartate;
glutamate --> alpha-KG