Smooth ER Functions and Drug Detoxification

Smooth ER Functions

The smooth ER has several functions, including:

  • Drug detoxification

  • Carbohydrate metabolism

  • Calcium storage

  • Steroid synthesis

Drug Detoxification

The liver is crucial for drug detoxification, which occurs in the smooth ER of liver cells. The goal is to make drugs more water-soluble so the kidneys can eliminate them more easily. Many drugs are hydrophobic, making it difficult for the kidneys to process them.

Cytochrome P450 Family

A family of enzymes called cytochrome P450 is found in the smooth ER of the liver. These enzymes hydroxylate hydrophobic drugs, adding a water molecule (e.g., an -OH group) to make them more water-soluble. Different enzymes within this family act on different chemicals.

Barbiturates (Phenobarbital) and Tolerance

  • Example: Phenobarbital

  • Rats given phenobarbital increase their production of these enzymes and the amount of smooth ER in liver cells (hepatocytes) to deal with the drug.

  • This adaptation leads to faster drug removal, which contributes to drug tolerance.

  • Tolerance: The same drug dosage has a reduced effect because the body becomes more efficient at eliminating it.

Risks of Losing Tolerance

If someone stops taking a drug, enzyme levels and the amount of smooth ER decrease. If they then resume the original dosage, their body may not be able to handle it due to the reduced enzyme levels. This can lead to overdose because the body is no longer as efficient at removing the drug.

Aryl Hydrocarbon Hydroxylase and Toxicity

  • Aryl Hydrocarbon Hydroxylase: An enzyme complex that hydroxylates polycyclic hydrocarbons (compounds with benzene rings).

  • The problem is that hydroxylation can make these compounds more toxic.

  • Increased aryl hydrocarbon hydroxylase levels in mice have been linked to increased cancer rates because the more toxic compounds have a higher chance of causing cell mutations.

Smoking and Cancer Risk

Smokers have increased amounts of aryl hydrocarbon hydroxylase in their bodies leading to an increased risk for cancers. They are putting more polycyclic hydrocarbons inside of them, and creating it in a more toxic form inside of them.why