"Microsomes"

 

Microsomes are small vesicular fragments derived from the endoplasmic reticulum (ER) when cells are disrupted during homogenization. They are not naturally occurring organelles but rather artifacts of cell fractionation, particularly from ultracentrifugation. Microsomes are widely studied in biochemistry and pharmacology due to their role in drug metabolism, protein synthesis, and lipid biosynthesis.

1. Formation of Microsomes

When cells are disrupted by homogenization and subjected to differential centrifugation:

• The nuclei and mitochondria pellet at lower speeds.
• The ER fragments, forming small vesicles, which are collected by high-speed ultracentrifugation (around 100,000 x g).
• These vesicles are called microsomes and retain the enzymatic properties of the ER.

Microsomes can be further classified into:

• Rough Microsomes → Derived from rough ER, contain ribosomes and are involved in protein synthesis.
• Smooth Microsomes → Derived from smooth ER, lack ribosomes, and are involved in lipid metabolism and detoxification.

2. Functions of Microsomes

Microsomes retain many key biochemical functions of the ER, including:

A. Drug Metabolism (Cytochrome P450 System)

• Microsomes, especially from the liver, contain high amounts of cytochrome P450 (CYP) enzymes, which are crucial for phase I drug metabolism.
• These enzymes catalyze oxidation, reduction, and hydrolysis reactions to make drugs more water-soluble for elimination.
• Important CYP enzymes include:
• CYP3A4 (metabolizes >50% of drugs)
• CYP2D6 (important for antidepressants, opioids)
• CYP2C9 (metabolizes NSAIDs, warfarin)

B. Protein Synthesis

• Rough microsomes contain ribosomes and mimic the rough ER in producing secretory and membrane-bound proteins.
• Proteins synthesized here undergo post-translational modifications like glycosylation.

C. Lipid Biosynthesis

• Smooth microsomes play a role in the synthesis of phospholipids, cholesterol, and steroid hormones.
• Liver microsomes are particularly important in cholesterol metabolism and bile acid formation.

D. Calcium Storage and Regulation

• Microsomes help regulate intracellular calcium levels, similar to the ER.
• This is crucial for muscle contraction, neurotransmitter release, and signal transduction.

3. Microsomes in Research and Drug Development

Microsomes are extensively used in in vitro drug metabolism studies, such as:

• Drug clearance prediction → Helps determine how quickly a drug is metabolized.
• Drug-drug interactions → Identifies inhibitors or inducers of CYP enzymes.
• Toxicology screening → Detects reactive metabolites that may cause toxicity.

Liver microsomes from different species (human, rat, monkey) help compare drug metabolism across organisms.

4. Clinical and Pharmacological Importance

• Hepatic Drug Metabolism: Liver microsomes are used to study how drugs are metabolized and eliminated.
• Xenobiotic Detoxification: Microsomes help metabolize toxins, pollutants, and drugs.
• Genetic Variability: Polymorphisms in CYP enzymes affect drug metabolism rates (fast vs. slow metabolizers).