Protein Biochemistry III Flashcards Preview

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Flashcards in Protein Biochemistry III Deck (25):
1

Which 2 AA contain sulfur?

1. Methionine - Essential
2. Cysteine - Non-essential

2

Describe the relationship between methionine, cysteine, and cystine

- can use methionine to make cysteine
- cystine is the oxidized version of cysteine

3

Disulfide bond importance?

- makes protein more stable
- allows for proteins to fold

* Note different redox environements

4

Redox environments in/out of cells

Outside: Oxidizing
Inside: Reducing

5

Sulfer AA degradation

1. 1st step of Met degradation produces activated sulfur (adoMet) --> SAM

2. SAM is more prevalent than ATP

Can go on and make Cys (Met + Ser = Cys)

6

Steps from met to cys

Met -(SAM synthetase)-> SAM -(MTases)-> SAH-(AdoHcyhydrolase)->homocysteine ->cysteine

Could also go from homocysteine back to Met via THF

7

Regeneration of met

- Requires 2 coenzymes
1. THF
2. Vit B12 (methyl group is transferred from THF to B12 to homocysteine)

8

How is PLP used here?

Holds again between:
1. Homocysteine and Cystathione
2. Cystathione and Cysteine

Note: alpha-ketobutyrate can go on to make succinyl CoA

9

Hyperhomocysteinemia and homocystinuria

come from 130 mutations identified in cystathione B-synthase

Can also come from low values of B6 and B12

Hyperhomocysteinemia: Tx is folate, B6 and B12
Homocystinuria: Tx with B6
Cysteinuria: Tx with acetazolamide to make cysteine more soluble

10

Homocysteine is bad

1. Vascular disease (NMDA)
2. Impaired wound healing
3. High correlation to cancer (cervical)

11

MTHFR

If this is broken, can get elevated levels of homocysteine

12

SAM

"energy storage unit" similar to ATP
- used for tx of lots of things because of methylation
- epigenetics; host defense
- cancer (methotrexate)
- depression

13

SAM and methylation

Methylation of NorE->Epi
Methylation of cytosine residues in DNA

14

Modified forms of THF do what?

Transfer carbons in different oxidation states

15

THF

1. Produced from Vit B9 (folic acid) by dihydrofolate reductase (DHFR)
2. Essential for synthesis of AA and nucleic acids

Note: Methotrexate can block this and nail cancer cells.

16

How are redox states controlled?

Glutathione (GSH)

17

GSH synthesis

Glutamate --> gamma-Glu-Cys --> GSH

Can form disulfides through Cys and can control redox chemistry of cell

18

Why is GSH important?

- more soluble compared to Cys
- Thiol acts as redox buffer to maintain reduced forms
- Cofactor for several enzymes
- reduce hydrogen peroxide to water and provides general protection against ROS

19

GSH in hemoglobin

- Keeps iron in frrous state
If Fe2+-->Fe3+, then cannot bind oxygen

20

3 important enzymes related to GSH

1. Glutathione peroxidase: GSH --> GSSG
- mutations lead to high BC risk
2. Glutathione reductase: reduces GSSG --> GSH
- mutations are rare but problematic for heme
3. Glutathione S-transferase: conjugation of GSH to agents
- detoxification, drug resistance, upregulated in tumors

21

3 aromatic residues

1. Trp
2. Phe
3. Tyr

22

Trp Metabolism

- metab to pyruvate or acetyl-CoA
- Trp --> serotonin, melatonin, niacin
- Tetrahydrobiopterin (BH4) cofactor required

23

Phe & Tyr metabolism

1. Phe --> Tyr via phenylalanine hydroxylase
2. Phe, Tyr metabolized to fumerate and acetoaceteate
3. Need BH4 as cofactor
4. Tyr --> catecholamines, melanin

PKU - defect in phenylalanine hydroxylase
Tyrosinemia - defect in one of 3 enzymes:
- fumarylacetoacetate
- Tyr aminotransferase
- hydroxyphenylpyruvate dioxygenase

24

PKU alternative pathway

- use a different transaminase (phenylalanine -> ketoacid; phenylpyruvate and phenylacetate - smelly in urine)
- Tyr becomes essential

25

Parkinson's

1. Treat with Dopa
2. Treat with MAOs or Mtase inhibitors
Block deamination to produce a buildup to offset ramifications of parkinson's