bchem seminar biochemistry important.pptx

Cytochrome p 450 detoxification

1. Cytochromes P450 are an important superfamily of heme-containing monooxygenases, and more than 50 such enzymes have been found in the human genome. They are located mainly in the endoplasmic reticulum in the liver and intestine, but are also found in the mitochondria in some 302 tissues. The cytochromes participate in an electron transport chain in which both NADH and NADPH may donate reducing equivalents. CYTOCHROME P450

2. Electrons are passed to cytochrome P450 in two types of reaction involving FAD or FMN. Class I systems consist of an FAD-containing reductase enzyme, an iron sulfur (Fe2S2 ) protein, and the P450 heme protein, while class II systems contain cytochrome P450 reductase, which passes electrons from FADH2 to FMN

3. INTRODUCTION 1-The cytochrome P450 is a superfamily of mono- oxygenases . 2-Heme-containing enzymes OR hemoproteins 3- Absorb light at a wavelength of 450nm.

4. 4- The substrate of CYP enzymes include -lipid and steroidal hormones -xenobiotics such as drugs and toxic chemical 5-CYPs are major enzymes involved in drug metabolism and bioactivation, accounting for about 75% of total metabolic reaction

5. Site 1- Present throughout the body 2- Act primarily in the ER of hepatocytes and the cells of intestine

6. P450 IN HUMAN Human CYPs are primarily membrane-associated proteins located either in the inner membrane of mitochondria or in the endoplasmic reticulum of cells

7. DRUG METABOLISM 1-CYP enzyme account for 75% of drug metabolism. 2-Most drug undergo deactivation by CYPs, either directly or by facilitated excretion from body 3-Also, many substances are bioactivated by CYPs to form their active compounds.

8. DRUG INTERACTION 1-Many drugs may increase or decrease the activity of various CYP isoenzyme 2-Inducing biosynthesis of an isoenzyme 3- Directly inhibiting the activity of CYP