5-Aminolevulinic acid hydrochloride
[CAS# 5451-09-2]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Amino acid salt
• Name: 5-Aminolevulinic acid hydrochloride
• Synonyms: 5-Amino-4-oxopentanoic acid hydrochloride; 5-Amino-4-ketovaleric acid hydrochloride
• Molecular Formula: C₅H₉NO₃.HCl;C₅H₁₀ClNO₃
• Molecular Weight: 167.59
• CAS Registry Number: 5451-09-2
• EC Number: 226-679-5
• SMILES: C(CC(=O)O)C(=O)CN.Cl

Properties

• Melting point: 150 °C (Decomposes) (Expl.)
• Solubility: DMSO: 35 mg/mL, Water: 34 mg/mL (Expl.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H335-H319
• Safety Statements: P261-P302+P352-P28-P305+P351+P338

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

5-Aminolevulinic acid hydrochloride is the hydrochloride salt of 5-aminolevulinic acid, a naturally occurring amino acid derivative that serves as a crucial intermediate in the biosynthesis of heme and other tetrapyrroles. The free base, 5-aminolevulinic acid (ALA), is synthesized in both plants and animals through different metabolic routes and represents the first committed precursor in the porphyrin biosynthetic pathway. Its discovery and role in biological systems have contributed significantly to the understanding of cellular respiration and photosynthesis.

The compound was first identified as part of the heme biosynthetic pathway in the early 20th century during efforts to elucidate the enzymatic steps involved in porphyrin formation. In animals, ALA is synthesized in the mitochondria from glycine and succinyl-CoA through the action of ALA synthase, an enzyme that is tightly regulated due to the essential role of heme as a cofactor in hemoglobin, cytochromes, and other hemoproteins. In plants and bacteria, an alternative biosynthetic route involving glutamate serves as the precursor to ALA. This duality in biosynthetic origin illustrates the evolutionary importance of the molecule across domains of life.

ALA hydrochloride was developed as a water-soluble and more stable form for pharmaceutical and agricultural uses. One of its most significant modern applications is in photodynamic therapy (PDT), especially for the treatment and diagnosis of certain types of cancer and precancerous lesions. When administered topically or systemically, ALA is preferentially taken up by rapidly proliferating cells and is metabolized into protoporphyrin IX (PpIX), a photosensitizer. Upon exposure to specific wavelengths of visible light, PpIX generates reactive oxygen species that cause localized cytotoxic effects, leading to selective destruction of diseased tissue while sparing the surrounding healthy cells. This property has been widely used in dermatology for treating actinic keratosis, basal cell carcinoma, and superficial squamous cell carcinoma.

Additionally, ALA hydrochloride has been applied in fluorescence-guided surgery, particularly for brain tumor resection. Patients ingest the compound orally, and within a few hours, malignant glioma cells accumulate fluorescent PpIX, which emits red fluorescence under blue light. This enables neurosurgeons to distinguish between tumor and healthy brain tissue during operation, significantly improving surgical precision and outcomes.

Beyond medical applications, 5-aminolevulinic acid and its hydrochloride salt have also attracted attention in agricultural science. ALA acts as a plant growth regulator and a promoter of photosynthesis, especially under suboptimal conditions such as low light or drought stress. By enhancing chlorophyll production and improving stress tolerance, ALA-based formulations are used to increase crop yield and quality. The compound is also being evaluated for its potential to reduce the environmental impact of traditional agrochemicals, offering a more sustainable approach to crop management.

Safety and regulatory evaluations have demonstrated that ALA hydrochloride exhibits low systemic toxicity and is generally well tolerated in clinical applications. However, due to its role in producing light-sensitive intermediates, careful control of light exposure is required following administration to avoid photosensitivity reactions in patients.

The versatility and biological relevance of 5-aminolevulinic acid hydrochloride have made it a valuable compound across multiple scientific and industrial domains. From basic research in porphyrin biosynthesis to cutting-edge clinical treatments and sustainable agriculture, the development and application of this molecule underscore the interplay between fundamental biochemistry and real-world innovation.

References

1994. Fluorescence photodetection of neoplastic urothelial lesions following intravesical instillation of 5-aminolevulinic acid. Urology, 44(6).
DOI: 10.1016/s0090-4295(94)80167-3

1979. delta-Aminolevulinic acid synthesis in a Cyanidium caldarium mutant unable to make chlorophyll a and phycobiliproteins. Archives of Biochemistry and Biophysics, 195(1).
DOI: 10.1016/0003-9861(79)90326-6

1987. Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins. British Journal of Cancer, 56(5).
DOI: 10.1038/bjc.1987.246