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Aminolevulinic acid Side effects

Views: 3     Author: Site Editor     Publish Time: 2023-03-29      Origin: Site

5-Aminolevulinic acid  an endogenous non-proteinogenic amino acid, is the first compound in the porphyrin synthesis pathway that leads to heme in mammals and chlorophyll in plants.5ALA for photodynamic detection and surgery of cancer.

Medical use

As a precursor of a photosensitizer, 5ALA is also used as an add-on to photodynamic therapy.In contrast to larger photosensitizer molecules, computer simulations predict that it will be able to penetrate tumor cell membranes.

Cancer diagnosis

Photodynamic detection is the use of light-sensitive drugs with light sources of the correct wavelength to detect cancer using the fluorescence of the drug.5ALA or its derivatives can be used to visualize bladder cancer by fluorescence imaging.

Cancer treatmentAminolevulinic acid powder

Aminolevulinic acid is being investigated for photodynamic therapy (PDT) in a variety of cancers.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 many gynecological cancers.Aminolevulinic acid for visualization of malignant tissue during surgery for malignant glioma (WHO grades III and IV) in adults.It is used to visualize tumor tissue during neurosurgery.Studies since 2006 have shown that intraoperative use of this guided approach reduces residual tumor volume and prolongs progression-free survival in patients with malignant glioma.The US FDA approved aminolevulinic acid hydrochloride (ALA HCL) for this use in 2017.

Side effects

Side effects may include liver damage and nerve problems.Hyperthermia may also occur.Death has also resulted.

Biosynthesis

In non-photosynthetic eukaryotes (such as animals, fungi, and protozoa) and the bacteria Alpha Proteus, it is produced by ALA synthase from glycine and succinyl-CoA.This response is known as the Shemin pathway and occurs in the mitochondria.In plants, algae, bacteria (except Alphaproteobacteria) and archaea, it is produced from glutamate via glutamyl-tRNA and glutamate-1-semialdehyde.The enzymes involved in this pathway are glutamyl-tRNA synthetase, glutamyl-tRNA reductase, and glutamyl-1-semialdehyde 2,1-aminomutase.This pathway is known as the C5 or Beale pathway.In most plastid-containing species, glutamyl-tRNA is encoded by plastid genes where transcription and subsequent steps of the C5 pathway occur.

Importance in humans

Activation of mitochondria:

In humans, 5ALA is the precursor of heme.The biosynthesized 5ALA undergoes a series of transformations in the cytosol and finally in the mitochondria to protoporphyrin IX.This protoporphyrin molecule is chelated with iron in the presence of ferrochelatase to produce heme.Heme increases mitochondrial activity, which helps activate the respiratory Krebs cycle and the electron transport chain leading to the formation of adenosine triphosphate (ATP), which provides sufficient energy for the body.

Accumulation of protoporphyrin IX:

Cancer cells lack or have reduced ferrochelatase activity, which leads to the accumulation of protoporphyrin IX, an easily visible fluorescent substance.

Induction of Heme Oxygenase-1 (HO-1):

Excess heme is converted to biliverdin and ferrous ions by the HO-1 enzyme in macrophages.The formed biliverdin is further converted to bilirubin and carbon monoxide.Biliverdin and bilirubin are potent antioxidants that regulate important biological processes such as inflammation, apoptosis, cell proliferation, fibrosis, and angiogenesis.

Plant

In plants, 5-ALA production is the step that regulates the rate of chlorophyll synthesis.Plants feeding on exogenous 5-ALA accumulate toxic amounts of the chlorophyll precursor prochlorophyll, suggesting that the synthesis of this intermediate is not inhibited any downstream in the reaction chain.Prochlorophyll is a strong photosensitizer in plants.However, controlled spraying of 5-ALA at lower doses (up to 150 mg/L) can help protect plants from stress and promote growth.