δ-Aminolevulinic acid (also dALA, δ-ALA, 5ALA, 5-ALA or 5-aminolevulinic acid), an endogenous non-proteinogenic amino acid, is the first compound in the porphyrin synthesis pathway, the pathway that leads to heme in mammals, as well as chlorophyll in plants.
5-ALA is used in photodynamic detection and surgery of cancer.
Medical uses
As a precursor of a photosensitizer, 5-ALA is also used as an add-on agent for photodynamic therapy. In contrast to larger photosensitizer molecules, it is predicted by computer simulations to be able to penetrate tumor cell membranes.
Cancer diagnosis
Photodynamic detection is the use of photosensitive drugs with a light source of the right wavelength for the detection of cancer, using fluorescence of the drug. It is not currently a first line treatment for Barrett's esophagus. Its use in brain cancer is currently experimental. It has been studied in a number of gynecological cancers.
Intra-operative cancer delineation
Aminolevulinic acid utilization is promising in the field of cancer delineation, particularly in the context of fluorescence-guided surgery. This compound is utilized to enhance the visualization of malignant tissues during surgical procedures.
When administered to patients, 5-ALA is metabolized to protoporphyrin IX (PpIX) preferentially in cancer cells, leading to their fluorescence under specific light wavelengths. This fluorescence aids surgeons in real-time identification and precise removal of cancerous tissue, reducing the likelihood of leaving residual tumor cells behind. This innovative approach has shown success in various cancer types, including brain and spine gliomas, bladder cancer, and oral squamous cell carcinoma.
5-ALA in gliomas
Aminolevulinic acid is indicated in adults for visualization of malignant tissue during surgery for malignant glioma (World Health Organization grade III and IV).
Studies since 2006 have shown that the intraoperative use of this guiding method may reduce the tumour residual volume and prolong progression-free survival in people with malignant gliomas. it has resulted in significantly higher rate of complete resections in malignant gliomas, compared to the traditional white-light resections. The use of 5-ALA has been described as an essential technique, and as standard-of-care at many neurosurgical departments worldwide.
Side effects
Side effects of administration may include liver damage and nerve problems.
In plants, algae, bacteria (except for the class Alphaproteobacteria) and archaea, it is produced from glutamic acid via glutamyl-tRNA and glutamate-1-semialdehyde. The enzymes involved in this pathway are glutamyl-tRNA synthetase, glutamyl-tRNA reductase, and glutamate-1-semialdehyde 2,1-aminomutase. This pathway is known as the C5 or Beale pathway. Its final step is the reaction:
In most plastid-containing species, glutamyl-tRNA is encoded by a plastid gene, and the transcription, as well as the following steps of C5 pathway, take place in plastids.
Importance in humans
Activation of mitochondria
In humans, 5ALA is a precursor to heme. This protoporphyrin molecule chelates with iron in presence of enzyme ferrochelatase to produce heme. leading to formation of adenosine triphosphate (ATP) for adequate supply of energy to the body. Biliverdin and bilirubin are potent antioxidants and regulate important biological processes like inflammation, apoptosis, cell proliferation, fibrosis and angiogenesis. Controlled spraying of 5-ALA at lower doses (up to 150 mg/L) can however help protect plants from stress and encourage growth.