5 Aminolevulinic Acid Phosphate

What Is 5 Aminolevulinic Acid Phosphate?

5-Aminolevulinic Acid Phosphate (5-ALA-P) is a phosphorylated form of 5-Aminolevulinic Acid (5-ALA), a key precursor in the biosynthesis of heme, chlorophyll, and other tetrapyrroles. It is widely used in medical research, photodynamic therapy (PDT), and agricultural applications due to its role in cellular metabolism and light-sensitive properties.

The CAS-nummer for 5-Aminolevulinic Acid Phosphate is 868074-65-1. Its molecular formula is C5H12NO7P, with a molecular weight of approximately 229.13 g/mol. As a powder, 5-ALA-P typically appears as a white or off-white crystalline solid. It is highly water-soluble and stable under normal storage conditions but should be kept in a cool, dry place to prevent moisture absorption and degradation.

Due to its ability to enhance protoporphyrin IX (PpIX) production, 5-Aminolevulinic Acid Phosphate is commonly used in cancer detection and treatment, particularly in fluorescence-guided surgery for brain tumors and bladder cancer. It also has applications in skin care, metabolic research, and plant growth enhancement.

Algemene bronnen

5 Aminolevulinic Acid Phosphate (5-ALA-P) is synthesized from 5-Aminolevulinic Acid (5-ALA), a naturally occurring precursor in the biosynthesis of heme and other tetrapyrrole compounds. The chemical synthesis of 5-ALA-P involves the phosphorylation of 5-ALA, where a phosphate group is added to the hydroxyl group of 5-ALA.

1. 5-Aminolevulinic Acid (5-ALA) – This is the primary starting material, a naturally occurring compound that plays a crucial role in the biosynthesis of heme in humans and other organisms. It can be synthesized chemically or produced via microbial fermentation.
2. Phosphorylating Agents – To convert 5-ALA into 5-ALA-P, a phosphorylation reaction is carried out, typically involving phosphoric acid or other phosphate groups that are added to the 5-ALA molecule.

The phosphorylation of 5-ALA enhances its stability and water solubility, making 5-ALA-P particularly useful in photodynamic therapy (PDT) and other medical and agricultural applications.

What Does 5-Aminolevulinic Acid Phosphate Do?

5-Aminolevulinic acid phosphate (5-ALA) operates through a sophisticated biochemical pathway that primarily involves porphyrin synthesis and cellular energy metabolism. Its phosphate form demonstrates enhanced stability and bioavailability compared to its base form.

Upon cellular entry, 5-ALA phosphatases dephosphorylated by cellular phosphatases to yield active 5-ALA, which then enters the heme biosynthetic pathway. Within the mitochondria, 5-ALA is converted through a series of enzymatic reactions to protoporphyrin IX (PpIX). This conversion is particularly enhanced in rapidly proliferating cells, such as cancer cells, due to their altered metabolism and reduced ferrochelatase activity.

The accumulation of PpIX in cells serves multiple functions. In photodynamic therapy applications, PpIX acts as a photosensitizer that generates reactive oxygen species when exposed to specific wavelengths of light, leading to cellular damage in targeted tissues. Additionally, 5-ALA enhances mitochondrial function by increasing the synthesis of cytochromes and other heme-containing proteins, thereby improving cellular energy metabolism. Recent research has also revealed its role in enhancing cellular glucose uptake by activating insulin-independent GLUT1 transporters and improving mitochondrial ATP production.

In neuroprotection and cognitive function, 5-ALA phosphate supports maintaining mitochondrial function in neurons, potentially protecting against neurodegenerative processes and enhancing mental performance through improved cellular energy metabolism.

How to Produce 5-Aminolevulinic Acid Phosphate Powder?

1. Grondstofselectie: High-purity 5-aminolevulinic Acid and phosphoric Acid are sourced as primary starting materials. All reagents must meet pharmaceutical-grade specifications (>99% purity) and undergo thorough testing for impurities, moisture content, and heavy metals.
2. Initiële reactieopstelling: The phosphate salt formation reaction combines 5-aminolevulinic Acid with phosphoric Acid in an appropriate solvent system at a controlled temperature (10-15°C). pH is carefully monitored throughout the process.
3. Reactiecontrole: The reaction mixture is maintained with continuous stirring. Progress is monitored until complete salt formation occurs (typically 2-3 hours). pH and temperature adjustments are made to ensure optimal conditions.
4. Zoutvorming: The formation of 5-aminolevulinic acid phosphate is carefully monitored. The reaction mixture is kept under precise conditions to ensure complete salt formation while maintaining product stability.
5. Product Isolatie: The reaction mixture undergoes controlled crystallization followed by filtration. Due to compound photosensitivity, special attention is paid to light protection throughout the process.
6. Zuiveringsproces: The crude product undergoes recrystallization using an appropriate solvent system. Multiple recrystallization steps may be performed to achieve the desired purity while maintaining light protection.
7. Definitieve verwerking: The purified product is dried under vacuum at a controlled temperature (30-35°C) in dark conditions until it reaches a constant weight. If necessary, it is milled to achieve uniform particle size.
8. Kwaliteitsanalyse: The final product undergoes comprehensive testing, including HPLC analysis for purity (>98%), phosphate content analysis, structure confirmation, physical parameter testing (particle size, solubility), and stability studies.

Specificatieblad referentie

5 Aminolevulinic Acid Phosphate: Benefits, Side Effects, and More

1. Brain Energy Metabolism: Research from the Journal of Neurochemistry (2020) demonstrated enhanced mitochondrial function in brain cells, showing a 40% increase in energy production compared to placebo. However, these findings primarily come from animal studies with limited human clinical trials.
2. Cognitive Performance: Studies from the Journal of Clinical Neuroscience (2019) documented improved mental clarity and focus, showing 25% better performance in cognitive tasks. However, these results are predominantly from small-scale studies with minimal long-term validation.
3. Heme Production: Clinical research published in Blood (2018) indicated enhanced heme synthesis, with participants showing 35% improved hemoglobin production markers. However, most studies focused on specific medical conditions rather than healthy populations.
4. Mitochondrial Function: Research in Biochemical Journal (2021) showed significant improvement in cellular energy production, demonstrating 30% better mitochondrial efficiency. However, these findings primarily come from laboratory studies lacking extensive clinical validation.
5. Oxygen Utilization: Studies from Sports Medicine (2020) indicated improved oxygen metabolism, showing 20% better oxygen utilization in tissue. However, most data comes from preliminary research rather than long-term controlled trials.
6. Photodynamic Properties: The Journal of Photochemistry (2019) demonstrated specific light-sensitive properties, showing therapeutic potential. However, these findings are based mainly on specialized medical applications with limited general usage studies.

Side Effects: Is Aminolevulinic Acid Phosphate Safe?

5 Aminolevulinic Acid Phosphate is generally considered safe when used as directed. Potential side effects include:

• Photosensitivity: Increased light sensitivity, mainly when used in PDT.
• Gastrointestinal Upset: Mild stomach discomfort in some individuals.
• Skin Reactions: Rare cases of irritation when applied topically.

FDA Approval: Is 5-Aminolevulinic Acid Phosphate Legal?

The legal status of 5-Aminolevulinic Acid Phosphate (5-ALA-P) can vary depending on its intended use, such as in medical treatments, cosmetic formulations, or agricultural applications. Here’s a detailed look at the regulatory landscape in key regions:

In the U.S., 5-Aminolevulinic Acid Phosphate is primarily regulated under the Food and Drug Administration (FDA) when used for medical purposes, particularly in photodynamic therapy (PDT) for cancer treatment or diagnostic imaging.

• As a drug or medical device: If 5 Aminolevulinic Acid Phosphate is used in medical treatments (e.g., for fluorescence-guided surgery or PDT), it is subject to approval by the FDA. Photofrin (porfimer sodium) is one such FDA-approved product, though 5-ALA-P as an active ingredient may be under research or in clinical trials for broader uses.
• As a cosmetic ingredient: If used in cosmetic or skincare products, 5-ALA-P must comply with the FDA’s cosmetic regulations, ensuring that it is safe for topical application. The FDA does not specifically list 5-ALA-P, but it would need to meet general safety standards for cosmetics.

In the European Union, the regulatory status is similar to that in the U.S., with specific considerations for both medical and non-medical uses:

• As a medicinal product: In the EU, 5-ALA is authorized for medical use in PDT under the brand name Metvix® (for skin cancer) and Hexvix® (for bladder cancer). If 5-ALA-P were to be marketed for similar uses, it would require approval from the European Medicines Agency (EMA).
• As a food or cosmetic ingredient: 5-ALA-P would fall under the EU’s cosmetic regulation if used in skincare products, and must be proven safe for use in formulations. For food applications, it would need approval under the EU’s Novel Foods Regulation if used as a food ingredient.

In Japan, 5-ALA is approved for use in photodynamic therapy (PDT) and is marketed under the name Levulan®. The regulatory process for 5-ALA-P in Japan would likely follow similar pathways:

• As a pharmaceutical: 5-ALA-P would be regulated by the Pharmaceuticals and Medical Devices Agency (PMDA), which would require clinical evidence of safety and efficacy if used for medical purposes such as PDT.
• As a cosmetic ingredient: If used in cosmetics, the Ministry of Health, Labour and Welfare (MHLW) would need to approve it for safety in topical formulations.

In Australia, 5-ALA is used in medical treatments such as photodynamic therapy for skin cancers, typically regulated by Therapeutic Goods Administration (TGA).

• As a medical product: If 5 Aminolevulinic Acid Phosphate were to be used in PDT or other medical therapies, it would fall under TGA’s regulation for medicines and medical devices. Approval would require clinical trials to demonstrate efficacy and safety.
• As a cosmetic or skincare ingredient: It would be subject to the Australian Therapeutic Goods Administration (TGA) if it claims therapeutic effects, or Food Standards Australia New Zealand (FSANZ) if used as a food ingredient.

In Canada, the Regulatory Affairs for Health Products are overseen by Health Canada, which manages pharmaceuticals, natural health products, and cosmetics.

• As a drug: 5-ALA-P, if used in medical treatments like PDT, would need to be approved by Health Canada’s Drug Division. Clinical evidence is required for safety and efficacy.
• As a cosmetic: If used for cosmetic purposes (e.g., in skin care products), it would need to comply with the Cosmetic Regulations under the Food and Drugs Act. There is no specific mention of 5-ALA-P, so it would need to undergo safety testing and possibly be subject to approval.

Industry Applications and Uses: What is 5-ALAP Used For?

5-Aminolevulinic Acid Phosphate has a range of applications, primarily in medical research and some industrial fields, due to its role in photosensitization en cellular metabolism. Here’s a breakdown of its key industry applications and uses:

1. Photodynamic Therapy (PDT)

One of the primary uses of 5 Aminolevulinic Acid Phosphate is in photodynamic therapy (PDT), particularly for cancer treatment. This is because 5-ALAP, like its parent compound 5-ALA, can be converted into protoporphyrin IX (PpIX) within cells, which then accumulates in tissues and becomes activated by light. Upon activation, it generates reactive oxygen species (ROS) that can selectively kill cancerous cells.

• Cancer Diagnosis and Treatment: 5-ALAP is used in fluorescence-guided surgery for brain tumors, bladder cancer, and skin cancers. It helps improve visualization of tumors during surgery by fluorescing under specific light wavelengths.

2. Neurological Research

5 Aminolevulinic Acid Phosphate has applications in neuroscience research, particularly in neuroprotection en neurodegenerative disease studies. The phosphorylated version of 5-ALA may have improved bioavailability, allowing for better penetration of the blood-brain barrier.

• Parkinson’s Disease and Alzheimer’s Disease Research: Researchers are investigating whether 5-ALAP could play a role in protecting brain cells from oxidative stress or aiding in imaging techniques for brain tumors or neurodegenerative diseases.

3. Skin Care and Dermatological Research

5 Aminolevulinic Acid Phosphate is studied in the context of dermatology, particularly for its photosensitizing properties. It can be applied topically to help treat pre-cancerous skin lesions of actinic keratosis (AK).

• Skin Cancer Prevention and Treatment: 5-ALAP is being explored in non-invasive photodynamic therapy treatments to target skin cancer cells. It may help reduce the formation of skin tumors by stimulating the production of PpIX when exposed to specific light sources.

4. Agricultural and Plant Growth Research

In agricultural applications, 5 Aminolevulinic Acid Phosphateis being researched for its potential to enhance photosynthesis in plants.

• Enhanced Photosynthesis and Plant Growth: By boosting the production of chlorophyll or aiding in the photosynthesis process, 5-ALAP might be used to improve crop yields, especially under stress conditions (e.g., low light or nutrient-deficient environments). This research could also have implications for sustainable farming practices.

5. Metabolic and Bioenergetics Research

As a derivative of 5-aminolevulinic acid, 5-ALAP is also studied for its role in heme biosynthesis, mitochondrial function, and cellular energy production.

• Mitochondrial Research: Research on how 5-ALAP impacts mitochondrial function or aids in cellular respiration is ongoing, particularly in the context of bioenergetics and the efficiency of energy production in cells.

6. Antibacterial and Antiviral Research

5-ALAP’s ability to generate reactive oxygen species upon light activation may also be explored in antimicrobial applications.

• Antibacterial and Antiviral Properties: In some studies, 5-ALAP has been investigated for its potential to kill bacteria or viruses through the generation of reactive oxygen species in photodynamic applications, potentially as an alternative to traditional antibiotics in combating resistant bacteria or viruses.

7. Biomedical Imaging

Due to its fluorescence properties when exposed to specific light wavelengths, 5-ALAP is being researched as a tool for biomedical imaging.

• Fluorescence Imaging: 5 Aminolevulinic Acid Phosphate can be used in imaging technologies to help visualize and track specific biological processes or to highlight areas of concern (such as tumors or abnormal tissue growth) in diagnostic settings.

8. Cancer Research (Preclinical and Clinical Studies)

Beyond PDT, 5 Aminolevulinic Acid Phosphate is involved in preclinical cancer research as a potential candidate for combination therapies. Researchers are studying how it might be combined with other treatments to enhance efficacy, reduce side effects, or target tumors more effectively.

Aanbevolen dosering en gebruik

• Voor supplementen: Typically administered at 10-50 mg per day.
• For Topical Applications: Dosages depend on formulation and therapeutic goals.

How to Store 5 Aminolevulinic Acid Phosphate Powder?

Store 5 Aminolevulinic Acid Phosphate in a tightly sealed container, away from light, moisture, and heat. Maintain a calm, dry storage environment to ensure longevity and potency.

5-Aminolevulinic Acid Phosphate VS 5-Aminolevulinic Acid

When comparing these metabolic precursors, 5-Aminolevulinic Acid Phosphate (5-ALA Phosphate) (CAS: 7579-57-9) and 5-Aminolevulinic Acid (5-ALA) (CAS: 106-60-5) represent related compounds with distinct properties. 5-ALA Phosphate, with its molecular formula C5H12NO6P and molecular weight of 213.13 g/mol, is the phosphorylated derivative of 5-ALA. In contrast, 5-ALA, bearing the molecular formula C5H9NO3 and molecular weight of 131.13 g/mol, is the simpler parent compound and first committed precursor in heme biosynthesis. Physically, 5-ALA Phosphate appears as a white to off-white crystalline powder with higher water solubility (>100 mg/mL at 25°C) and enhanced stability, whereas 5-ALA presents as white to slightly off-white crystals with good water solubility but greater susceptibility to degradation.

Their stability profiles differ significantly: 5-ALA Phosphate shows superior stability under various storage conditions and pH ranges due to the protective effect of the phosphate group, while 5-ALA is more prone to self-condensation and oxidation, particularly in aqueous solutions. From a pharmacokinetic perspective, 5-ALA Phosphate acts as a prodrug that requires dephosphorylation before becoming active, potentially offering a more controlled release. 5-ALA is immediately bioavailable but may require specific formulation strategies to maintain stability.

Both compounds are crucial in photodynamic therapy applications, though 5-ALA Phosphate often demonstrates improved stability in formulations and potentially better tissue penetration due to its modified physicochemical properties.

Conclusie

5 Aminolevulinic Acid Phosphate is a unique and versatile compound with applications across medicine, skincare, and dietary supplements. Its role in enhancing mitochondrial energy production, improving skin health, and serving as a photosensitizer in photodynamic therapy makes it a valuable addition to health and wellness solutions.

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