Aminolevulinic acid

δ-Aminolevulinic acid
Clinical data
Pregnancy; category	C;
ATC code	L01XD04 (WHO) ;
Legal status
Legal status	In general: ℞ (Prescription only);
Identifiers
	IUPAC name 5-amino-4-oxo-pentanoic acid;
CAS Number	106-60-5 ;
PubChem CID	137;
IUPHAR/BPS	4784;
DrugBank	DB00855 ;
ChemSpider	134 ;
UNII	88755TAZ87;
KEGG	D07567 ;
ChEBI	CHEBI:356416 ;
ChEMBL	ChEMBL601 ;
CompTox Dashboard (EPA)	DTXSID8048490 ;
ECHA InfoCard	100.003.105
Chemical and physical data
Formula	C5H9NO3
Molar mass	131.13 g/mol g·mol−1
3D model (JSmol)	Interactive image;
Melting point	118 °C (244 °F)
	SMILES O=C(CN)CCC(=O)O;
	InChI InChI=1S/C5H9NO3/c6-3-4(7)1-2-5(8)9/h1-3,6H2,(H,8,9) ; Key:ZGXJTSGNIOSYLO-UHFFFAOYSA-N ;
	(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 Alphaproteobacteria class of bacteria, it is produced by the enzyme ALA synthase, from glycine and succinyl CoA. This reaction is known as the Shemin pathway, which occurs in mitochondria.^[1]

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.^[2]^[3] 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.^[4]

Clinical significance

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]

5-Aminolevulinic acid, or derivatives thereof, can be used to visualize bladder cancer by fluorescence imaging.

Cancer treatment with PDT

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.

Fluorescence-guided surgery (eg for cancer)

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.^[6] 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.^[7]^[8]

References

^ Ajioka, James; Soldati, Dominique, eds. (September 13, 2007). "22". Toxoplasma: Molecular and Cellular Biology (1 ed.). Taylor & Francis. p. 415. ISBN 9781904933342.
^ 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.
^ Willows, R.D. (2004). "Chlorophylls". In Goodman, Robert M. (ed.). Encyclopaedia of Plant and Crop Science. Marcel Dekker. pp. 258–262. ISBN 0-8247-4268-0.
^ Biswal, Basanti; Krupinska, Karin; Biswal, Udaya, eds. (2013). "22". Plastid Development in Leaves during Growth and Senescence (Advances in Photosynthesis and Respiration). Dordrecht: Springer. p. 508. ISBN 9789400757233.
^ Wagnieres, Georges (2014). Detection of bladder cancer by fluorescence cystoscopy: From bench to bedside - The Hexvix story. CRC Press. p. 411edition=M. Hamblin, Y-Y Huang. ISBN 978-1-4398-8469-0.
^ 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.
^ 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.
^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

[1] Ajioka, James; Soldati, Dominique, eds. (September 13, 2007). "22". Toxoplasma: Molecular and Cellular Biology (1 ed.). Taylor & Francis. p. 415. ISBN 9781904933342.

[2] 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.

[3] Willows, R.D. (2004). "Chlorophylls". In Goodman, Robert M. (ed.). Encyclopaedia of Plant and Crop Science. Marcel Dekker. pp. 258–262. ISBN 0-8247-4268-0.

[4] Biswal, Basanti; Krupinska, Karin; Biswal, Udaya, eds. (2013). "22". Plastid Development in Leaves during Growth and Senescence (Advances in Photosynthesis and Respiration). Dordrecht: Springer. p. 508. ISBN 9789400757233.

[5] Wagnieres, Georges (2014). Detection of bladder cancer by fluorescence cystoscopy: From bench to bedside - The Hexvix story. CRC Press. p. 411edition=M. Hamblin, Y-Y Huang. ISBN 978-1-4398-8469-0.

[6] 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.

[7] 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.

[8] 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)

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