Important players in the biosynthesis of L-phenylalanine include DAHP synthase (DS) and chorismate mutase/prephenylate dehydratase (CM/PD). While CM/PD is susceptible to feedback inhibition by L-phenylalanine, DS is susceptible to feedback inhibition by tyrosine [1]. With an IC50 of 980 μM, L-phenylalanine can reduce the activity of non-NMDA receptors in cultured neurons [5].

The patch-clamp method was used to examine the impact of L-phenylalanine on NMDA-activated currents (INMDA) in cultured rat hippocampus neurons. With an IC50 of 1.71 mM, L-phenylalanine selectively and reversibly reduces IMDA in a concentration-dependent manner. By competing with glycine binding sites, L-phenylalanine selectively suppresses NMDAR currents in hippocampus neurons [3].

Absorption, Distribution and Excretion
Absorbed from the small intestine via sodium-dependent active transport. …It diffuses across the placental membrane, with fetal serum concentrations higher than maternal concentrations. In rhesus monkeys, when maternal serum concentrations near term are 1–2 mg/100 mL, the diffusion ratio is approximately 1.5:1; however, when maternal concentrations are…higher (25 mg/100 mL), fetal serum…concentrations can reach 45 mg/100 mL, which is harmful to the fetus. /Phenylalanine/ Although free amino acids dissolved in body fluids constitute only a small fraction of the total amino acids in the body, they are crucial for the nutritional and metabolic control of proteins in the human body. …While plasma is the easiest to sample, most amino acids are found in higher concentrations in intracellular pools within tissue cells. Typically, large neutral amino acids, such as leucine and phenylalanine, are essentially in equilibrium with plasma. Other amino acids, particularly glutamine, glutamate, and glycine, are 10 to 50 times more concentrated in intracellular pools than in plasma. Dietary changes or pathological conditions can lead to significant changes in the concentrations of various free amino acids in plasma and tissue pools.
Table: Comparison of the size of free amino acid and protein-bound amino acid pools in rat muscle [Table #3668]

---

Metabolism/Metabolites
Hepatic metabolism. L-phenylalanine not metabolized in the liver is distributed to various tissues of the body via systemic circulation and undergoes metabolic reactions in tissues similar to those in the liver.
Amino acid metabolic pathway - L-phenylalanine; oxidative deamination or transamination product: phenylpyruvic acid. Decarboxylation product: phenylethylamine. Phenylalanine is converted to tyrosine.
L-phenylalanine in humans produces: N-acetyl-L-phenylalanine; benzoic acid; possibly 2,5-dihydroxy-L-phenylalanine in humans. /From Table/
L-phenylalanine in humans produces: phenylethylamine; phenylpyruvic acid; L-tyrosine. /From Table/
L-phenylalanine in rats produces Lm-tyrosine. /From Table/
For more complete data on the metabolism/metabolites of (L)-phenylalanine (12 in total), please visit the HSDB record page.
Hepatic Metabolism. L-phenylalanine not metabolized in the liver is distributed to various tissues of the body via systemic circulation and undergoes metabolic reactions in these tissues similar to those in the liver.

Toxicity Summary
Phenylketonuria (PKU) is a congenital metabolic disorder (IEM) characterized by extremely high serum phenylalanine levels. At typical pathological concentrations in PKU, phenylalanine self-assembles into fibers with an amyloid-like morphology and ordered electron diffraction. These fibers and the amyloid deposits they form in the brain appear to be partly responsible for neurological tissue damage in PKU patients (A8160). Studies have also shown that extremely high plasma phenylalanine concentrations increase phenylalanine entry into the brain, thereby limiting the entry of other macro- and neutral amino acids. Deficiencies in macro- and neutral amino acids may lead to disordered brain protein synthesis, which is particularly important in young children (A8162). The potential antidepressant activity of L-phenylalanine may be related to its precursor role in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated levels of norepinephrine and dopamine in the brain are thought to be associated with antidepressant effects. The possible anti-vitiligo activity mechanism of L-phenylalanine is not fully understood. It is speculated that L-phenylalanine may stimulate melanin production in affected skin.

---

Interactions
After intraperitoneal injection of 0.8 mg ochratoxin A and 0.8 mg phenylalanine, 97% of the animals survived; after injection of 1 mg phenylalanine, 100% of the animals survived.

---

Non-human toxicity values
The intraperitoneal LD50 for rats was 5287 mg/kg.

[1]. Long-term changes in glutamatergic synaptic transmission in phenylketonuria. Brain. 2005 Feb;128(Pt 2):300-7.

[2]. L-phenylalanine selectively depresses currents at glutamatergic excitatory synapses. J Neurosci Res. 2003 Apr 1;72(1):116-24.

[3]. Specific inhibition of N-methyl-D-aspartate receptor function in rat hippocampal neurons by L-phenylalanine at concentrations observed during phenylketonuria. Mol Psychiatry. 2002;7(4):359-67.

[4]. Structure-activity relationships of alpha-amino acid ligands for the alpha2delta subunit of voltage-gated calcium channels. Bioorg Med Chem Lett. 2006 Mar 1;16(5):1138-41.

[5]. Enhancement of l-phenylalanine production in Escherichia coli by heterologous expression of Vitreoscilla hemoglobin. Biotechnol Appl Biochem. 2018 May;65(3):476-483.

Therapeutic Uses
A necessary aromatic amino acid, it is a precursor to melanin, dopamine, norepinephrine, and thyroxine.
/Experimental Treatment/ Currently, there is no completely effective treatment for vitiligo (localized hypopigmentation). Oral or topical psoralen photochemotherapy is generally considered the best treatment option, but experimental therapies include phenylalanine UVA phototherapy. In a study of 200 vitiligo patients, oral doses of up to 100 mg/kg of phenylalanine combined with UVA/sunlight irradiation resulted in good therapeutic effects in over 90% of patients. Early-stage patients showed the most significant efficacy, but long-term use can still lead to pigment regeneration in patients with longer disease duration. Pigment regeneration primarily occurs in areas rich in hair follicles. This therapy is contraindicated in patients with phenylketonuria and pregnant women. Similarly, an open-label study reported that among 149 patients treated with 50 to 100 mg/kg of phenylalanine daily combined with twice-weekly UVA irradiation, 94 patients experienced remission. However, only 22% of the responding patients achieved pigment regeneration in over 60% of the affected areas. Higher doses did not appear to be more effective than 50 mg/kg daily. Another research group reported their six-year experience treating vitiligo with 50 or 100 mg/kg daily phenylalanine, combined with topical application of 10% phenylalanine gel and daily sun exposure. Although not ideal, they considered this treatment method useful, especially in terms of rapid facial pigmentation regeneration. The same research group also conducted an open-label study, adding topical application of 0.025% clobetasol propionate and UV exposure during the fall and winter seasons; 65.5% of patients achieved complete facial pigmentation recovery. /Experimental Therapy/ L-Phenylalanine (Phe) is a potent satiety hormone cholecystokinin (CCK) releaser. Previous studies, primarily in men, have shown that Phe intake reduces energy intake. This study aimed to test the effect of Phe on energy intake in overweight and obese women. In a subject-specific, balanced, double-blind study, subjects (n = 32) received three treatments 20 minutes before lunch and dinner: a high-dose group (10 g Phe), a low-dose group (5 g Phe and 5 g glucose), or a control group (10 g glucose). No effect of Phe was observed; however, post-hoc analysis revealed an interaction with dietary restriction. L-phenylalanine combined with 0.025% clobetasol propionate under sunlight on sunny days or under UVA lamps in winter appears to improve progressive vitiligo without side effects and is therefore particularly recommended for use on the face or in children. For more complete data on the therapeutic uses of (L)-phenylalanine (7 types), please visit the HSDB records page.

---

Drug Warning
Overweight and obese women (n = 32) received three treatments (high dose (10g phenylalanine), low dose (5g phenylalanine and 5g glucose), or control (10g glucose)) 20 minutes before their casual lunch and dinner. High doses of phenylalanine increased nausea scores.

---

Pharmacodynamics
Phenylalanine is used by the brain to produce norepinephrine, a chemical that transmits signals between nerve cells and the brain; it keeps people awake and alert; reduces hunger; has antidepressant effects; and helps improve memory.Pharmacodynamics

C9H11NO2

165.1891

165.078

63-91-2

L-Phenylalanine benzyl ester hydrochloride;2462-32-0;L-Phenylalanine-d7;69113-60-6;L-Phenylalanine-d8;17942-32-4;L-Phenylalanine-13C9,15N;878339-23-2;L-Phenylalanine-d5;56253-90-8;L-Phenylalanine-d2;221346-31-2;DL-Phenylalanine-d5;284664-89-7;L-Phenylalanine-3-13C;136056-02-5;L-Phenylalanine-13C9;439685-11-7;L-Phenylalanine-d;54793-54-3;L-Phenylalanine-15N,d8;L-Phenylalanine-13C;81201-86-7;L-Phenylalanine-15N;29700-34-3;DL-Phenylalanine-d5 hydrochloride;L-Phenylalanine-13C6;180268-82-0;L-Phenylalanine-13C9,15N,d8;1994331-22-4

6140

White to off-white solid powder

1.2±0.1 g/cm3

307.5±30.0 °C at 760 mmHg

270-275ºC (dec.)(lit.)

139.8±24.6 °C

0.0±0.7 mmHg at 25°C

1.576

1.11

2

3

3

12

153

1

C1=CC=C(C=C1)C[C@@H](C(=O)O)N

COLNVLDHVKWLRT-QMMMGPOBSA-N

InChI=1S/C9H11NO2/c10-8(9(11)12)6-7-4-2-1-3-5-7/h1-5,8H,6,10H2,(H,11,12)/t8-/m0/s1

(2S)-2-amino-3-phenylpropanoic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O : ~6.67 mg/mL (~40.38 mM)

Solubility in Formulation 1: 9.09 mg/mL (55.03 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication (<60°C).

---

 (Please use freshly prepared in vivo formulations for optimal results.)