Aminolevulinic acid

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δ-Aminolevulinic acid
Aminolevulinic acid.svg
Clinical data
Trade names NatuALA
License data
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
CAS Number
PubChem CID
ECHA InfoCard 100.003.105
Chemical and physical data
Formula C5H9NO3
Molar mass 131.13 g·mol−1
3D model (JSmol)
Melting point 118 °C (244 °F)

δ-Aminolevulinic acid (also dALA, δ-ALA, 5ala or 5-aminolevulinic acid) an **endogenous nonprotein amino acid ,is the first compound in the porphyrin synthesis pathway, the pathway that leads to heme in mammals and chlorophyll in plants. It is marketed as an adjuvant in Japan, UAE, Bahrain and Jordan for prediabetic, diabetic patients and patients with metabolic syndrome.

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.


In non-photosynthetic eukaryotes such as animals, 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]

Importance in humans[edit]

Activation of mitochondria[edit]

In humans, 5Ala is precursor of heme (Fig. 1). Biosynthesized, 5 ALA goes through a series of transformations in the cytosol and finally gets converted to Protoporphyrin IX inside the mitochondria. This protoporphyrin molecule chelates with iron in presence of enzyme ferrochelatase to produce Heme [5].Heme has been reported to increase mitochondrial activity thereby helping in activation of respiratory system (Krebs Cycle and Electron Transport Chain) [6] leading to formation of ATP for adequate supply of energy to the body.

Accumulation of Protoporphyrin IX[edit]

Cancer cells lack or have reduced ferrochelatase activity and this results in accumulation of Protoporphyrin IX, a fluorescence generating substance, that can easily be visualized [7].

Induction of Heme Oxygenase-1 (HO_1)[edit]

Excess heme is converted in macrophages to biliverdin and ferrous ions by the enzyme HO-1. Biliverdine formed further gets converted to bilirubin and carbon mono oxide. Biliverdine and bilirubin are potent anti oxidants and regulate important biological processes like inflammation, apoptosis, cell proliferation, fibrosis and angiogenesis[8].

Clinical significance[edit]

Looking at the wide variety of pathways where 5 ALA gets involved it has a potential to be used in variety of diseases specifically the ones which are classified under mitochondrial diseases apart from it approved use for photodynamic therapy and photo dynamic detection.

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

Cancer diagnosis[edit]

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.[7].5-Aminolevulinic acid, or derivatives thereof, can be used to visualize bladder cancer by fluorescence imaging. Cancer treatment with PDT[edit].

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[edit]

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 (e.g. for cancer)[edit]

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 since 2006 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] The US FDA approved aminolevulinic acid hydrochloride (ALA HCL) for this use in 2017.[9]

Adjuvant in Prediabetics and Type II Diabetes Mellitus Patients[edit]

As a precursor of heme in human body, 5 ALA increases mitochondrial activity thereby stimulating respiratory system (Krebs Cycle and Electron Transport Chain). 5 ALA increases the activity of cytrochrome C oxidase activity[6] resulting in utilization of glucose for production of ATP. 5 ALA in combination with sodium ferrous citrate (SFC) has been reported to be well tolerated in both diabetic and prediabetic individuals and results in reduction of HbA1C, fasting blood glucose and 2 hour oral glucose tolerance levels [13-16].

Other therapeutic effects[edit]

5 ALA in combination with SFC has been reported for lowering of LDL, triglycerides and total cholesterol in patients[17]. This combination (5ALA + SFC) has also been studied in variety of other diseases and it has been found to help in improvement of sexual health[17], energy levels[17] and reduction of lactate levels[18]. The combination of 5ALA and SFC has also been reported for improvement of veisalgia[19] (hangover due to overindulgence in alcohol) and for improvement of renal functioning in chronic renal diseases[20]. This nephroprotective activity has been attributed induction of HO-1 by 5ALA[8].

See also[edit]


  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. PMC 1062668Freely accessible. PMID 16667613. doi:10.1104/pp.93.4.1273. 
  3. ^ 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. 
  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. PMID 23358480. doi:10.1038/nrneurol.2012.279. 
  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. PMID 16648043. doi:10.1016/S1470-2045(06)70665-9. 
  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. PMC 3458892Freely accessible. PMID 23049761. doi:10.1371/journal.pone.0044885. 
  9. ^ FDA Approves Fluorescing Agent for Glioma Surgery. June 2017