Protein Biochemistry I Flashcards Preview

DEMS Unit 2 Part 2 > Protein Biochemistry I > Flashcards

Flashcards in Protein Biochemistry I Deck (23):
1

What two post-translational modifications of AA lead to collagen?

Hydroxyproline and Hydroxylysine

2

What mediates interstrand H-bonds formed by Hyp

Water molecules; increases strength of fibrils

3

What enzyme creates interstrand x-links between lys & hyl

lysyl oxidase

- schiff base (covalent interaction)

4

Hyp vs. Hyl interactions

Hyp: electrostatic interstrand H-bonds
Hyl: covalent interstrand X-links

5

Prolyl Hydroxylase
Lysl Hydroxylase

Prolyl hydroxylase converts Pro to Hyp
Lysyl hydroxylase converts Lys to Hyl

Both require ascorbate (lack of Vit C leads to Scurvy - reduced strength of collagen fibrils)

6

Scurvy patho

Reduced vascular endothelium --> hemorrhages --> loss of RBCs --> swollen gums, bruising, anemia

7

Gamma-carboxyglutamate

Glu --(Gamma-glutamyl carboxylase) --> gamma carboxyglutamate

-Vit K dependent
- Important because negative charge at terminus and chelation of heavy metal = bury the negative charge
- Charge normally on outside of protein except membrane proteins

8

Prothrombin uses Gla to target membranes

- N-terminal domain of prothrombin is "Gla domain"
- Gla domain contains 10 Gla residues that bind Ca
- Partially embeds into membrane (yellow)

9

2 ways to degrade proteins

1. Ubiquination pathway targets enzymes to the proteasome and is ATP-dependent
2. The lysosome engulfs extracellular proteins to mix with digestive enzymes

10

Ubiquitin-proteasome mechanism

To get to the proteasome, have to go through a shuttle of 3 enzymes (E1, E2, and E3)

- 1st step is ATP-dependent: conjugates E1 to Ubiquitin; done through a cysteine thioester bond
- Shuttled from there and is not ATP-dependent
- At the end, the E3-E2 complex dictate which substrate gets marked with ubiquitin for degradation
- Proteasome cuts protein into pieces and recycles ubiquitin

11

Do all ubiquitinated things go to the garbage?

No-- some are involved in signaling

12

Lysosome

-engulfs extracellular proteins to mix with digestive enzymes
- engulf larger material such as bacteria as well
- contains hydrolytic enzymes that include aspartic proteases

13

Enzymatic degradation in stomach and small intestine

Stomach: pepsin (aspartic protease)

Intestine: trypsin, chymotrypsin, (serine proteases) carboxypeptidase A and B (metalloproteases)

Acidically activated from zymogen form at low pH

14

Enteropeptidase

Activates trypsinogen --> trypsin
Activates procarboxypeptidsase-A &B--> carboxypeptidase A&B

15

Aminotransferases

Transfer amino groups

L-amino acid --> alpha keto acid

16

Transamination reactions

- Reversible reaction Keq = 1
- Major goal is to produce Asp and NH3 for Urea cycle
- 100s of aminotransferases that are selective for a few AA
- Mostly in cytosol
- Increased levels indicate liver damage/disease

17

2 most important aminotransferases

1. ALT --> pyruvate
2. AST --> oxaloacetate

18

Glutamate acts as a shuttle for which products?

1. Free ammonia for urea cycle
2. Aspartic acid for urea cycle

19

Pyridoxal Phosphate (PLP)

- Vitamin B6
- A required coenzyme for aminotransferases
- "holds" the amino group and waits for another reaction to occur
- active form is the phosphorylated form of B6

20

Schiff base

This is when PLP kept around, held in place by the aminotransferase so that it can do another reaction

21

Control points for protein catabolism

1. Directionality of transamination is regulated by relative concentrations of substrates and products (regulating nitrogen entry into urea cycle)

2. N-acetylgutamate is required activator of carbamoyl phosphate synthetase I that kick starts the urea cycle

3. The directionality of oxidative deamination by Glu dehydrogenase depends on the relative concentrations of GLU, alpha-ketoglutarate, NH3

4. ATP & GTP are allosteric inhibitors of Glu dhydroenase while ADP & GDP are activators

22

Purpose of the Urea Cycle

Get rid of ammonia because there is no storage

Ammonia is toxic in the blood - can cause cerebral edema, coma, and death

23

Overall sum of Urea Cycle Reactions

- Need 3 ATP to go through the cycle once
- 2 Entry points of nitrogen (free ammonia, and aspartate)