5-Aminolevulinic acid
[CAS# 106-60-5]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives
• Name: 5-Aminolevulinic acid
• Synonyms: 5-Amino-4-oxovaleric acid
• Protein Sequence: v
• Molecular Formula: C₅H₉NO₃
• Molecular Weight: 131.13
• CAS Registry Number: 106-60-5
• EC Number: 203-414-1
• SMILES: C(CC(=O)O)C(=O)CN

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 298.4±20.0 ºC 760 mmHg (Calc.)^*
• Flash point: 134.3±21.8 ºC (Calc.)^*
• Index of refraction: 1.482 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Discovory and Applicatios

5-Aminolevulinic acid (5-ALA) is a naturally occurring δ-amino acid that plays a critical role in the biosynthesis of heme, chlorophyll, and other tetrapyrrole compounds. Structurally, it consists of an amino group and a ketone group on a five-carbon backbone. In living organisms, 5-ALA is synthesized either via the Shemin pathway in animals and fungi or through the C5 pathway in plants, algae, and many bacteria. In the latter, glutamate is the precursor, converted by glutamyl-tRNA reductase and glutamate-1-semialdehyde aminotransferase to form 5-ALA.

The discovery of 5-ALA dates back to the early 20th century during studies on porphyrin metabolism. Its role as the universal precursor of tetrapyrroles was confirmed in the mid-1900s through biochemical studies tracing the synthesis of heme and chlorophyll. By labeling precursor molecules with isotopes, researchers demonstrated that 5-ALA is incorporated into the porphyrin ring system of heme and chlorophyll, linking it to critical processes such as respiration and photosynthesis.

In medicine, 5-ALA is extensively used as a prodrug in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). Tumor cells preferentially accumulate 5-ALA-derived protoporphyrin IX (PpIX), a photosensitizer. Upon irradiation with specific wavelengths of light, PpIX generates reactive oxygen species that selectively destroy tumor cells. This approach has been especially effective in gliomas, bladder cancer, and skin lesions. 5-ALA is commonly administered orally or topically before light exposure, and fluorescence imaging allows clinicians to visualize tumor margins with high precision. The FDA has approved 5-ALA under the trade name Gleolan® for fluorescence-guided surgery in high-grade gliomas.

Beyond oncology, 5-ALA is used in dermatology to treat actinic keratosis and acne vulgaris. It also holds potential in cardiovascular and metabolic research due to its involvement in mitochondrial function and energy metabolism. In agriculture, 5-ALA has been investigated as a biodegradable plant growth regulator, improving photosynthetic efficiency, stress tolerance, and crop yield under suboptimal conditions. Unlike many synthetic agrochemicals, 5-ALA is environmentally friendly and degrades naturally without persistent residues.

Biosynthetic production of 5-ALA using genetically engineered microbes such as *Escherichia coli* and *Corynebacterium glutamicum* has enabled sustainable and cost-effective manufacturing. Enhancements in fermentation technologies and metabolic pathway optimization have led to increased yields, making 5-ALA commercially viable for medical and agricultural applications. Several studies have focused on overexpressing key enzymes or deleting feedback-inhibition pathways to optimize productivity.

While 5-ALA is generally considered safe, high concentrations may induce phototoxicity in exposed tissues, especially in PDT applications. Clinical protocols regulate dosage and light exposure to minimize such adverse effects. Regulatory agencies in Europe, North America, and Asia have approved 5-ALA-based products for clinical and commercial use.

Ongoing research is exploring novel applications of 5-ALA in imaging, gene therapy, and nanomedicine. Coupling 5-ALA with nanoparticles or combining it with immunotherapy could enhance selectivity and therapeutic efficacy. In plant sciences, the focus has shifted toward understanding how 5-ALA modulates photosynthesis at the molecular level and its synergy with other bio-stimulants.

Overall, 5-ALA serves as a versatile and multifaceted compound bridging fundamental biochemistry with applied sciences. Its discovery has not only deepened our understanding of porphyrin biosynthesis but also paved the way for targeted clinical interventions and environmentally sustainable agricultural practices.

References


Sasaki K, Watanabe M, Tanaka T (2002) Biosynthesis, biotechnological production and applications of 5-aminolevulinic acid. Applied Microbiology and Biotechnology 58 1 23–29 DOI: 10.1007/s00253-001-0858-7


Ishizuka M, Abe F, Sano Y, Takahashi K, Inoue K, Nakajima M, Ogura SI, Tanaka T (2011) Novel development of 5‑aminolevulinic acid (ALA) in cancer diagnoses and therapy. International Immunopharmacology 11 3 358–365 DOI: 10.1016/j.intimp.2010.11.029


Tetard MC, Vermandel M, Leroy HA, Leroux B, Maurage CA, Reyns N (2016) Interstitial 5‑ALA photodynamic therapy and glioblastoma: preclinical model development and preliminary results. Photodiagnosis and Photodynamic Therapy 13 218–224 DOI: 10.1016/j.pdpdt.2015.07.169