Biochemistry

Biotransformation of xenobiotics and endogenous toxins in the liver: microsomaloxidation,

cytochromeР-450.

Xenobiotic is a chemical substance found within an organism that is not naturally produced or expected
to be present within the organism. It can also cover substances that are present in much higher
concentrations than are usual

1. Types of reactions of biotransformations of xenobiotics in a liver?

Phases of biotransformation

Enzyme Phase I Phase II Phase II

Types of Hydrolysis Conjugation – Conjugated
reaction Oxidation by cytochrome P40 attachment of an metabolites are
Reduction ionized group to the excreted through
drug e.g. Acetyl, Methyl, urine or feces via
Glutathione. bile
Increase in small Large
hydrophilicity
General Exposes functional group Polar compound added
mechanism to functional group
Consequence May result in metabolic activation. Drug inactivated
Note the drug still active Facilitates excretion
Example Oxidized to salicylic acid Its conjugated with Excreted in the
Aspirin glycine or glucuronic urine
acid forming a range of
ionized metabolites

2. Reactions of microsomal oxidation; inductors and aninductors of microsomal monooxygenases?

The microsomal ethanol oxidizing system (MEOS) is an alternate pathway of ethanol metabolism that
occurs in the smooth endoplasmic reticulum in the oxidation of ethanol to acetaldehyde.

The MEOS pathway converts ethanol to acetaldehyde by way of a redox reaction. In this reaction,
ethanol is oxidized (losing two hydrogens) and O2 is reduced (by accepting hydrogen) to form H2O.
NADPH is used as donor of hydrogen, forming NADP+. This process consumes ATP and dissipates heat

Microsomal Enzymes Non-Microsomal Enzymes

Smooth endoplasmic reticulum of cells of liver, Cytoplasm, mitochondria of hepatic and other
kidney, lungs and skin tissue
Nonspecific Inducible Non Inducible
PHASE 1: most oxidation and reduction, some PHASE 1: most hydrolysis and some oxidation &
hydrolysis reduction
 PHASE 2: only glucuronide conjugation PHASE 2: all except glucuronide conjugation
Cytochrome P450 Mono amine oxidase, alcohol dehydrogenase

3. Reactions of conjugation in the hepatocytes: biochemical mechanisms, functions.

4. The role of cytochrome Р-450 in biotransformation of xenobiotics?

Cytochrome P450 is a family of enzymes involved in

1. Drug metabolism
2. Bio activation
3. Breakdown of xenobiotics – hence turns drugs into soluble molecules so that it can be secreted
out properly

Active site of Cytochrome P450 has a heme center i.e. iron with a porphyrin ring surrounding it where
the iron is bound to the 4 nitrogen atoms and the thiol of the cysteine residue

5. Clinical significance of liver functions’ evaluating (indican’s and hypuric acid qualitative reactions)?