Aminolevulinic acid

δ-Aminolevulinic acid
Systematic (IUPAC) name
5-amino-4-oxo-pentanoic acid
Clinical data
  • C
  • ℞ (Prescription only)
Identifiers
106-60-5 Yes
L01XD04
PubChem CID 137
DrugBank DB00855 Yes
ChemSpider 134 Yes
UNII 88755TAZ87 Yes
KEGG D07567 Yes
ChEBI CHEBI:356416 Yes
ChEMBL CHEMBL601 Yes
Chemical data
Formula C5H9NO3
131.13 g/mol
 Yes (what is this?)  (verify)

δ-Aminolevulinic acid (dALA or δ-ALA or 5ala or 5-aminolevulinic acid ) is the first compound in the porphyrin synthesis pathway, the pathway that leads to heme in mammals and chlorophyll in plants.

In plants, production of δ-ALA is the step on which the speed of synthesis of chlorophyll is regulated. Plants that are fed by external δ-ALA accumulate toxic amounts of chlorophyll precursor, protochlorophyllide, indicating that the synthesis of this intermediate is not suppressed anywhere downwards in the chain of reaction. Protochlorophyllide is a strong photosensitizer in plants.

Biosynthesis

In non-photosynthetic eukaryotes such as animals, insects, fungi, and protozoa, as well as the α-proteobacteria group of bacteria, it is produced by the enzyme ALA synthase, from glycine and succinyl CoA. This reaction is known as the Shemin pathway.

In plants, algae, bacteria (except for the α-proteobacteria group) 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.[1][2]

Clinical significance

It elicits synthesis and accumulation of fluorescent porphyrins (protoporphyrin IX) in epithelia and neoplastic tissues, among them malignant gliomas. It is used to visualise tumorous tissue in neurosurgical procedures.[3] Studies have shown that the intraoperative use of this guiding method may reduce the tumour residual volume and prolong progression-free survival in patients suffering from this disease.[4][5]

Being a precursor of photosensitizer, aminolevulinic acid is also a used as an agent for photodynamic therapy.

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.

5-Aminolevulinic acid can be used to visualize bladder cancer.[6]

Cancer treatment

Photodynamic therapy (PDT) treatment possibilities include those for cancer of the prostate, breast, giant BCC (skin), cervix, recurrent bladder, vulvar, brain (human glioblastoma cells), HPV, lung, stomach, head and neck, penis, and colon, as well as those for leukemia, Barrett's esophagus, squamous cell carcinoma (SCC), Bowen's disease, and other types of cancer.

See also

References

  1. ↑ Beale SI (August 1990). "Biosynthesis of the Tetrapyrrole Pigment Precursor, delta-Aminolevulinic Acid, from Glutamate". Plant Physiol. 93 (4): 1273–9. doi:10.1104/pp.93.4.1273. PMC 1062668. PMID 16667613.
  2. ↑ Willows, R.D. (2004). "Chlorophylls". In Goodman, Robert M. Encyclopaedia of Plant and Crop Science. Marcel Dekker. pp. 258–262. ISBN 0-8247-4268-0.
  3. ↑ Eyüpoglu, Ilker Y.; Buchfelder, Michael; Savaskan, Nic E. (2013). "Surgical resection of malignant gliomas—role in optimizing patient outcome". Nature Reviews Neurology 9 (3): 141–51. doi:10.1038/nrneurol.2012.279. PMID 23358480.
  4. ↑ Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ (2006). "Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial". Lancet Oncol. 7 (5): 392–401. doi:10.1016/S1470-2045(06)70665-9. PMID 16648043.
  5. ↑ Eyüpoglu, Ilker Y.; Hore, Nirjhar; Savaskan, Nic E.; Grummich, Peter; Roessler, Karl; Buchfelder, Michael; Ganslandt, Oliver (2012). Berger, Mitch, ed. "Improving the Extent of Malignant Glioma Resection by Dual Intraoperative Visualization Approach". PLoS ONE 7 (9): e44885. doi:10.1371/journal.pone.0044885. PMC 3458892. PMID 23049761.
  6. ↑ "Bacillus Calmette-Guérin Immunotherapy for Bladder Cancer Overview of BCG Immunotherapy".