Cytochrome P450

Question 1

Cytochrome P450 are involved in

Answer 1

• Production of steroid hormones
• Metabolim of fatty acids and prostaglandins
• Conversion of chemicals in to high reactive molecules
• Enzyme inhibition and induction to cause drug-drug interactions

Question 2

Cytochrome P450 electron transport system, explin how it goes!

Answer 2

I) NADPH provides 2 e to FAD.

II) FAD provides 1 e at a time to FMN.

III) FMN transfers the electrons one at a time to Cytochrome P450.

Question 3

Explain the cytochrome P450 monoxygenase reaction cycle!

Answer 3

I) Substrate binds to ferric heme
II )First electron is transferred to heme converting t to a high spin penta coordinate ferrous heme
III) Oxygen binds to ferrous heme and second electron transfer is initiated
IV)Subsequently molecular oxygen is cleaved forming H20 and another atom is inserted to substrate

Question 4

Cytochrome P450 convert cholesterol to steroid hormones. Can you give a few examples?

Answer 4

Aldosterone in adrenal cortex- regulates water and salt balance
Cortisol in adrenal cortex - protein carbohydrate and lipid metabolism
Testosterone in testis
Estradiol i ovaries

Question 5

CYP21A2 defect, what leads it to???

Answer 5

Congenital adrenal hyperplasia,.

Defect in CYP21A2 leads to increased prod of ACTH.
ACTH leads to increased prod of androgenic hormones.

Question 6

Steroid hormone prod during pegnancy?

Answer 6

Placenta becomes major producer of progesterone which lacks CYP17. So it cleaves the side chain to form pregnelone from cholesterol. Oxidizes pregnelone to form progesterone.

Question 7

2 phases of metabolizing xenobiotics, explain!

Answer 7

Phase I: hydroxyl group is added.

Phase II: connects functionsl group to glucoronic acid, sulfate or glutathione to make compound more soluable and eaier to excrete.

Question 8

How is benzo a pyrene a carcinogen?

Answer 8

Benzo a pyrene is a weak carcinogen formed by burning of coal. But after reacting with cYPs in the body it causes mutations by binding to guanine in DNA.

Question 9

Explain acetaminophen metabolism!

Answer 9

Usually acetaminophen is taken care by glucoronidation or sulfation, but in higher amounts it is metabolised by CYP2E1. Then it becomes NAPQ1, it can be taken care of glutathione, but if not, then it becomes toxic.

Question 10

What are the components of NOS?

Answer 10

It contsins a oxygenase domain and reductase domain.

The reductase domain works the same as in the CP450 reductase, with NADPH, FAD and FMN.

The oxygenase domain consists of hydrobiopterin, heme, and arg