Lecture 10. Enzymology 2 Flashcards
What does the drug methotrexate (trexall) do and what enzyme does it inhibit ?
- Oncology and inflammatory disease
What does the drug astoravatin (lipitor) do and what enzyme does it inhibit ?
- Reduces cholesterol levels
2. HMG-CoA reductase
What is a lipitor ?
A statin which inhibits synthesis of cholestrol
In competitive inhibition, what is the Vmax ?
The Vmax is unchanged because inhibition can be overcome by a sufficiently high concentration of substrate
What is mixed inhibition (non-competitive) ?
The inhibitor binds to both the enzyme or enzyme substrate complex
What is an uncompetitive inhibition ?
The inhibitor binds only to the enzyme substrate complex in what is essentially substrate dependent inhibition
What is a competitive inhibitor ?
The inhibitor is structurally similar to the substrate and can bind to the active site, preventing the actual substance from binding
Are humans effected by sulfanilamide ?
No, because humans get folic acid in their diet
What is the function of sulfanilamide ?
Mimics p-aminobenzoic acid (PABA), which is a metabolite needed by bacteria for synthesis of the coenzyme folic acid. It binds to the enzyme that normally metabolises PABA and competitively inhibits it, preventing folic acid synthesis
What does the drug oceltamivir (tamiflu) do and what enzyme does it inhibit ?
- Influenza
2. Viral neuraminidase
What does the drug lmatinib (gleevec) do and what enzyme does it inhibit ?
- Oncology
2. BCR-ABL Kinase
What does the drug siloenofil (viagra) do and what enzyme does it inhibit ?
- Pulmonary artery hypertension and erectile dysfunction
2. Type 5 phosphodiecterase
What does the drug fluoxetire (prozac) do and what enzyme does it inhibit ?
- Antidepressant
2. Pre-synaptic seretonin receptors
What stabilises the tetrahedral reaction intermediate ?
Oxyanion hole (region in the active site)
What does asparate do to serine 195 ?
Orients the histidine and renders it a better proton acceptor
What does the alkoxide ion do to the substrate ?
Attacks the peptide bond
What is histidine’s role in serine 195 ?
Histidine acts as a base catalyst, removing a proton from serine 195 and generating a highly reactive alkoxide ion
What is serine part of ? Name the other members of the group.
A catalytic triad. With histidine and aspartate
What is the only group specific reagent that only modifies serine 195 ?
Disopropylphosphofluoridate
What happens to serine 195 during catalysis ?
It becomes a strong nucleophile that attacks the carbonyl group of the peptide bond in the substrate
What is the function of chymotrypsin ?
Hydrolyzes peptide bonds selectively on the carboxyl side of the large hydrophobic residues
Where is chymotrypsin secreted from ?
The pancreas
What type of enzyme is chymotrypsin ?
A proteolytic enzyme
Is protein hydrolysis exergonic or endergonic
Exergonic but kinetically very slow
