Liver Lobule ~ glucuronidation

GLUCURONIC ACID CONJUGATION 

Condensation of the drug or its primary metabolite with d-glucuronic acid (dextro

Glucuronyl transferase

GLUCURONIC ACID CONJUGATION  enzyme

• uridine diphosphate glucuronic acid) UDPGA

GLUCURONIC ACID CONJUGATION  coenzyme

Glucuronic acid

GLUCURONIC ACID CONJUGATION  small ionizable

• Glutathione conjugation

To make the drug non toxic

Cofactor

pertain to the substances that are needed by certain enzymes to carry out catalysis of a particular chemical reaction

Acetylation, & Methylation

Produce inactive metabolite

• Glucuronidation, sulfate conjugation, & amino acid conjugation 

make the drug polar

• Conjugation or synthetic reactions.

PHASE 2 REACTION aka

PHASE 2 REACTION

• Conjugation or addition of a molecule from an endogenous substance to the parent compound.

RBC IN METABOLISM

Use as drug protein binding site

RBC in metabolism

• Has no nucleus, no mitochondria, no ribosomes, or mRNA, it cannot synthesize protein. 

RBC in metabolism

• Equipped with numerous enzyme systems (energy supply for the cell protection of hemoglobin and cell membrane from oxidation).

Local anesthetic

Drugs that undergoes ester & amide hydrolyis are

amide (amidase)

acid + amine

ester (esterase)

acid + alcohol

Azoreduction

Sulfasalazine & Protonsil pathway

Oxidation

• Most common in phase 1

4

CYP3A4

• Individual gene

A

CYP3A4

Subfamily

3

CYP3A4

Family

CYP

CYP3A4

Root

CYP3A4

Most common isoform

Most abundant

1. CYP 3A4

2. CYP 2D6

3. CYP 2C8

CYP

electron acceptor

CYP450 is the

electron donor

NADPH (serves as

electron transporter

Flavoprotein

CYP450 & Flavoprotein

MFO contains enzyme which is

• Mixed Function Oxidases aka Monooxygenase Enzyme

Enzyme for phase 1 reaction called

Synthetic or conjugation reaction.

PHASE 2 REACTION aka

PHASE 2 REACTION

• A molecule provided by the body is added to the drug.

Functionalization Phase

PHASE 1 REACTION

• aka.

Functionalization Phase

Phase 1

• non-synthetic phase.

Isoniazid

Some drugs undergo first  phase 2 before phase 1 like

CYP450

most important isoenzymes responsible for liver metabolism

• CYP 1, 2, 3, and 4

Involved in drug metabolism:

1. Reactant (drug or xenobiotics).

2 Reaction catalyst (enzymes)

3. Product (metabolite).

3 MAJOR COMPONENTS OF A DRUG BIOTRANSFORMATION

Acidic metabolites

• often excreted from the body by active secretion in the renal tubule 

• (1) make the drug Inactive, (2) make the drug less toxic, (3) make the drug Polar ~ Excretion

Goal for metabolism;

Prodrug

• initially Inactive but after Metabolism they become Active

BIOACTIVATED METABOLITE

• Parent drug (-)

• Metabolite (+)

• The parent drug now is the prodrug

METABOLITE that retain similar ACTIVITY

• Parent drug (+)

• Metabolite (+)

METABOLITES THAT RETAIN SIMILAR ACTIVITY

• Parent drug (+)

• Metabolites (+)

• If both of the are (+) means prolong action

Metabolites

The product of metabolism is called

Mitochondria

Metabolizing enzymes (found in

Bile acids

Secreted by the Liver

Gallbladder

Bile is stored in the

• Endothelial lining of the sinusoids 

Kupffer cells 

Kupffer cells 

• Phagocytic macrophages

• Reticulo Endothelial System 

Kupffer cells part of the

Sinusoids

• Large vascular capillaries.

Sinusoids

Facilitates drug and nutrient removal before the blood enters the general circulation.

Hepatic portal vein

• Collects blood from the various segments of the GIT that perfuse in (to) the liver.

Hepatic portal vein

• Carries nutrient (from the GIT) to the liver.

Hepatic portal vein

• Liver to heart

Hepatic artery

Perfused blood in the liver

Hepatic artery

Carries oxygen in the liver

Hepatic artery

pump/ moves (blood) away from the Heart towards the Organ

Large right lobe

left lobe

(2) Liver Lobule

parenchymal cells

a network of interconnected lymph and blood vessels

Liver Lobule

Contains parenchymal cells

Liver Lobule

Basic unit of the liver.