5-Aminolevulinic acid (5-ALA) is a naturally occurring compound found across various forms of life, including humans, animals, plants, bacteria, and fungi. It plays a fundamental role in biological processes, serving as a foundational molecule for the creation of complex structures within cells. The compound is non-toxic to humans and animals and degrades easily in the environment.
Understanding 5-Aminolevulinic Acid
5-ALA functions as a precursor molecule within the heme biosynthesis pathway. A precursor is a substance from which another substance is formed through a chemical reaction. 5-ALA is the initial compound in the pathway that leads to the production of tetrapyrrole compounds, including chlorophyll in plants and heme in humans and animals. Its involvement in creating heme, a component of hemoglobin, highlights its importance for cellular functions, particularly in oxygen transport and energy production.
How 5-ALA Works in the Body
When administered, 5-ALA is converted through enzymatic steps into Protoporphyrin IX (PpIX). This conversion occurs within the heme biosynthesis pathway, bypassing the body’s natural feedback control mechanisms that regulate heme production. PpIX then selectively accumulates in rapidly dividing or abnormal cells, such as cancerous cells, at higher concentrations than in healthy cells. This selective accumulation is attributed to altered enzyme activity within the heme synthesis pathway in cancer cells, particularly a reduced activity of ferrochelatase, the enzyme that converts PpIX into heme.
Cancer cells also exhibit an increased uptake of 5-ALA due to higher expression of specific transporters. Once accumulated, PpIX becomes a photosensitizer. This means it can absorb specific wavelengths of light and then release this absorbed energy. This energy release can occur as fluorescence, emitting a red glow, or by transferring energy to molecular oxygen, generating reactive oxygen species (ROS). These ROS are highly reactive and can cause damage to cellular components, leading to cell death.
Medical Applications of 5-ALA
5-ALA is utilized in medical settings primarily through two distinct applications: Photodynamic Therapy (PDT) and Fluorescence-Guided Surgery (FGS).
Photodynamic Therapy (PDT)
In PDT, 5-ALA is applied topically or administered systemically to induce PpIX accumulation in targeted abnormal cells. The treated area is then exposed to specific wavelengths of light, typically red light, activating the accumulated PpIX. This activation generates reactive oxygen species, which selectively destroy abnormal cells while minimizing damage to surrounding healthy tissue. PDT with 5-ALA is approved for treating conditions such as actinic keratosis, which are precancerous skin lesions, and certain superficial skin cancers, including basal cell carcinoma.
Fluorescence-Guided Surgery (FGS)
In FGS, particularly for certain brain tumors, 5-ALA is given orally to the patient several hours before the procedure. The accumulated PpIX in tumor cells fluoresces a distinct red or pink color when illuminated by a special microscope with a blue light filter during surgery. This fluorescence allows neurosurgeons to more clearly distinguish tumor tissue from healthy brain tissue, facilitating a more complete and precise removal of cancerous cells. This method offers real-time guidance, beneficial in identifying infiltrative tumor margins not visible with standard white light or conventional imaging.
Patient Experience and Safety
Patients undergoing 5-ALA treatments receive the compound either as a topical cream for skin conditions or as an oral solution for internal applications like brain tumor surgery. For topical treatments, a gel containing 5-ALA is applied to the affected skin area. For internal applications, an oral dose is usually taken a few hours before the procedure.
The most common side effect associated with 5-ALA administration is photosensitivity, meaning an increased sensitivity to light. This occurs because PpIX, the photosensitizing metabolite of 5-ALA, can accumulate in skin cells in addition to target cells. Patients are advised to avoid direct sunlight and bright indoor light for at least 24 to 48 hours after administration to prevent skin reactions such as redness, blistering, or peeling. Other potential, though less common, side effects may include nausea, vomiting, a temporary decrease in blood pressure, or mild, transient elevations in liver enzymes. Following medical advice regarding light exposure and other post-treatment care is important for patient safety and to minimize adverse reactions.