Cytochromes Flashcards
What type of enzyme phase is Cytochrome P450?
Major Phase 1 enzyme
What do Cytochromes P450 work on?
- Drugs
- Poisonous compounds
- Carcinogens from eating or breathing
What do Cytochromes P450 make?
Essential molecules (ie: steroids)
What is the abbreviation for Cytochromes P450?
CYP450
What is the definition of isoform?
Member of a family based on its homology
What type of enzyme is CYP450?
Mono-oxygenases
What protein is associated with CYP450?
Integral membrane protein with a single heme group
What membrane is associated with CYP450?
Membrane by an N-terminal membrane anchoring sequence
Where can you find CYP450?
Systolic side
Where can you find the enzyme systems of CYP450?
Endoplasmic reticulum (microsomal; 50/57) and Mitochondria (7/57)
What is the complexity of CYP450?
Multi-enzyme complex
What distinguishes Phase 1 from Phase 2?
Makes more metabolites that are more polar
Under what conditions will CYP450 take over metabolism of drugs?
Hypoxic conditions when there is not enough O2 in the body
What type of metabolism is CYP450 associated with?
Xenobiotic metabolism
Where can Lipophilic Xenobiotics be found in?
They are found in therapeutic drugs, food additives, and environmental contaminants
True or False: CYP isoforms are discriminating.
False: they are less discriminating as they have higher availability, have a variety of substrates, and have multiple sites of oxidation
What are the three possible outcomes for the metabolism of xenobiotics and drugs?
- Inactivation (drug metabolism)
- Activation (prodrug conversion: codeine to morphine)
- Formation of a highly toxic metabolite (metabolism of acetaminophen to NAPQI)
True or False: Xenobiotics/drugs induce CYPs
True: CYPs are inducible and inhabitable at the genetic (DNA) level
How do CYPs metabolize compounds at a genetic (DNA) level?
Via binding cis- and trans- activating elements that cause transcription
Which binding is more common in CYPs metabolism?
Cis-binding
Why is trans-binding less common in CYPs metabolism?
Because trans-binding would require the unwinding of the DNA
Why can xenobiotics/drugs inhibit CYPs via binding?
Because binding would prevent transcription
Describe what happens with Rifampicin in relation to CYPs
Rifampicin is an anti-tuberculosis drug that upregulates CYP3A4. The rate of metabolism of clearance (of drugs) through the liver increases, which means that the elimination of warfarin increases. This leads to the risk of undertreating patients
Describe what happens with St. John’s wort in relation to CYPs
St. John’s wort is an herbal medicine that is believed to treat mild depression without the need of a prescription. It induces CYP3A4
