Protein Biochemistry III Flashcards
Which 2 AA contain sulfur?
- Methionine - Essential
2. Cysteine - Non-essential
Describe the relationship between methionine, cysteine, and cystine
- can use methionine to make cysteine
- cystine is the oxidized version of cysteine
Disulfide bond importance?
- makes protein more stable
- allows for proteins to fold
- Note different redox environements
Redox environments in/out of cells
Outside: Oxidizing
Inside: Reducing
Sulfer AA degradation
- 1st step of Met degradation produces activated sulfur (adoMet) –> SAM
- SAM is more prevalent than ATP
Can go on and make Cys (Met + Ser = Cys)
Steps from met to cys
Met -(SAM synthetase)-> SAM -(MTases)-> SAH-(AdoHcyhydrolase)->homocysteine ->cysteine
Could also go from homocysteine back to Met via THF
Regeneration of met
- Requires 2 coenzymes
1. THF
2. Vit B12 (methyl group is transferred from THF to B12 to homocysteine)
How is PLP used here?
Holds again between:
- Homocysteine and Cystathione
- Cystathione and Cysteine
Note: alpha-ketobutyrate can go on to make succinyl CoA
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
Homocysteine is bad
- Vascular disease (NMDA)
- Impaired wound healing
- High correlation to cancer (cervical)
MTHFR
If this is broken, can get elevated levels of homocysteine
SAM
“energy storage unit” similar to ATP
- used for tx of lots of things because of methylation
- epigenetics; host defense
- cancer (methotrexate)
- depression
SAM and methylation
Methylation of NorE->Epi
Methylation of cytosine residues in DNA
Modified forms of THF do what?
Transfer carbons in different oxidation states
THF
- Produced from Vit B9 (folic acid) by dihydrofolate reductase (DHFR)
- Essential for synthesis of AA and nucleic acids
Note: Methotrexate can block this and nail cancer cells.
How are redox states controlled?
Glutathione (GSH)
GSH synthesis
Glutamate –> gamma-Glu-Cys –> GSH
Can form disulfides through Cys and can control redox chemistry of cell
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
GSH in hemoglobin
- Keeps iron in frrous state
If Fe2+–>Fe3+, then cannot bind oxygen
3 important enzymes related to GSH
- Glutathione peroxidase: GSH –> GSSG
- mutations lead to high BC risk - Glutathione reductase: reduces GSSG –> GSH
- mutations are rare but problematic for heme - Glutathione S-transferase: conjugation of GSH to agents
- detoxification, drug resistance, upregulated in tumors
3 aromatic residues
- Trp
- Phe
- Tyr
Trp Metabolism
- metab to pyruvate or acetyl-CoA
- Trp –> serotonin, melatonin, niacin
- Tetrahydrobiopterin (BH4) cofactor required
Phe & Tyr metabolism
- Phe –> Tyr via phenylalanine hydroxylase
- Phe, Tyr metabolized to fumerate and acetoaceteate
- Need BH4 as cofactor
- Tyr –> catecholamines, melanin
PKU - defect in phenylalanine hydroxylase
Tyrosinemia - defect in one of 3 enzymes:
- fumarylacetoacetate
- Tyr aminotransferase
- hydroxyphenylpyruvate dioxygenase
PKU alternative pathway
- use a different transaminase (phenylalanine -> ketoacid; phenylpyruvate and phenylacetate - smelly in urine)
- Tyr becomes essential
