Metabolism

Question 1

Explain CYP P450 Nomenclature

Answer 1

CYP = abbreviation for Cytochrome P450
2 = designates family
D = designates sub-family
6 = designates specific gene/enzyme

Italicised = gene that codes for cytochrome
Non-italicised = mRNA or protein product of CYP gene

Question 2

What is the major CYP in the liver?

Answer 2

CYP3A4

Question 3

Explain the effects of CYP inhibition.

Answer 3

Inhibition of presystemic oxidation increases drug in the body

• Causes drug-drug interactions and possible toxicity
• Grapefruit juice can inhibit intestinal metabolism

Question 4

Explain the effects of CYP induction.

Answer 4

Clinical significance;

• Increased clearance of drugs metabolised by CYP’s
• Decreased systemic exposure
• Diminished therapeutic effect of oral contraceptives, anticancer drugs, antihypertensives etc.

Question 5

Define Gene Polymorphisms and the two types.

Answer 5

Single Nucleotide Polymorphism (SNP): 
o	GAATTTAAG 
o	GAATTCAAG 
Variable number of tandem repeats (VNTR): (here 2bp-CA) 
o	(4) CACACACA
o	(7) CACACACACACACA
o	(6) CACACACACACA

Question 6

Describe the impact of Single Nucleotide Polymorphisms on CYP function.

Answer 6

SNPs can affect CYP;

• Protein function
• Rate of metabolism
• Amount of protein synthesised