Phenylalanine

Phenylalanine is an essential aromatic amino acid that must be obtained from the diet because humans cannot synthesize it. It serves primarily as a building block for proteins and as a precursor for several neuroactive compounds, most notably the neurotransmitters dopamine, norepinephrine, and epinephrine, as well as the pigment melatonin. By supplying the substrate for these pathways, phenylalanine contributes to normal brain function, mood regulation, and metabolic signaling.

• Molecular Formula and Weight: Phenylalanine (L‑phenylalanine) is an α‑amino acid with the molecular formula C₉H₁₁NO₂ and a molecular weight of 165.19 g mol⁻¹.
• IUPAC Name and Structure: IUPAC name: (2S)-2‑amino‑3‑phenylpropanoic acid. It possesses an aromatic phenyl side chain (benzyl group) attached to the α‑carbon, giving it hydrophobic character, while the amino (–NH₂) and carboxyl (–COOH) groups confer amphipathic properties.
• Enantiomer Activity: The L‑enantiomer is biologically active, whereas the D‑form is not incorporated into proteins and is metabolized slower.
• Solubility and Properties: Phenylalanine is a zwitterion at physiological pH (≈7.4) and is soluble in water (~28 g/L at 25 °C).
• Biological Roles: It is a substrate for phenylalanine hydroxylase (requiring tetrahydrobiopterin as a cofactor) and participates in the aromatic amino‑acid transport system (LAT1/2).
• pKa Values: Its pKa values are ≈2.2 (carboxyl) and ≈9.1 (amino).

• Natural Sources: Naturally, phenylalanine is abundant in high‑protein foods: meat, fish, eggs, dairy, soy, nuts, and legumes.
• Commercial Production: Commercially, it is produced by fermentation of glucose using genetically engineered Corynebacterium or E. coli strains that over‑express phenylalanine biosynthetic enzymes, yielding a highly pure L‑form.
• Alternative Synthesis: An alternative chemical synthesis (Strecker or reductive amination) is also used but is less common due to higher impurity risk.
• Supplement Source: For supplements, the preferred source is fermentation‑derived L‑phenylalanine, which meets GMP standards and is free of animal‑derived contaminants.
• Quality Considerations: Quality considerations include verification of L‑enantiomer purity (>99 %), absence of heavy metals, and low residual endotoxin levels. Certified “pharmaceutical‑grade” products are typically produced under GMP and are tested for the presence of phenylalanine‑related metabolites that could indicate contamination with other amino acids.