Phenylalanine ( Phe or F)
- An essential amino acid that is used to make tyrosine. Like tyrosine, it is the precursor of catecholamines (adrenalin-like substances) in the body (tyramine, dopamine, epinephrine, and norepinephrine).
- Phenylalanine is an amino acid with the formula HO2CCH(NH2)CH2C6H5. The codons for L-phenylalanine are UUU and UUC.
- Classified as nonpolar because of the hydrophobic nature of the benzyl side chain.
- Phenylalanine is structurally closely related to dopamine, epinephrine (adrenaline) and tyrosine.
- It is a direct precursor to the neuromodulator phenylethylamine, a commonly used dietary supplement.
- Phenylalanine is highly concentrated in the human brain and plasma.
- Used by the brain to produce Norepinephrine, a chemical that transmits signals between nerve cells and the brain
- L-phenylalanine can also be converted into L-tyrosine, another one of the DNA-encoded amino acids. L-tyrosine, in turn, is converted into L-DOPA, which is further converted into dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). The latter three are known as the catecholamines.
- Has an energizing effect, useful for treating depression and lethargy.
- d-phenylalanine-not used the same as natural L form but may help with chronic pain, lower back, and dental pain.
- Can raise blood pressure to dangerous levels, especially for those taking MAO inhibitors as antidepressants.
- Do not take if you have phenylketonuria.
- Combined form treats chronic pain of osteoarthritis and rheumatoid arthritis, lower back pain, menstrual cramps, and migraines.
- Blocks certain enzymes in the Central nervous system that is responsible for breaking down the brain's own painkillers.
- A hereditary condition and cant metabolize phenylalanine properly. If left untreated, mental retardation and poor muscle coordination can result.
- Extremely high serum levels of phenylalanine are found in patients with the inborn error of metabolism (IEM) called Phenylketonuria (PKU).
- At pathological concentrations typical of PKU, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These fibrils and their resulting amyloid deposits that localize to the brain appear to be partially responsible for the neural tissue damage seen in PKU patients.
- It has also been suggested that very high plasma phenylalanine concentrations can increase phenylalanine entry into the brain and thereby restrict the entry of other large neutral amino acids. The lack of large neutral amino acids may lead to disturbed cerebral protein synthesis, which is particularly important for young children.
- Phenylalanine should be avoided by phenylketonurics and pregnant women. Phenylketonurics, who have a genetic error of phenylalanine metabolism, have elevated serum plasma levels of phenylalanine up to 400 times normal.
- Mild phenylketonuria can be an unsuspected cause of hyperactivity, learning problems, and other developmental problems in children.
- Phenylalanine is neurotoxic. Chronic exposure to very high levels of phenylalanine in the blood (as found in phenylketonuria, or PKU) can lead to a build-up in the cerebrospinal fluid and brain, leading to seizures, organ damage and unusual posture. Complications of PKU include severe intellectual disability, brain function abnormalities, microcephaly, mood disorders, irregular motor functioning, and behavioral problems such as attention deficit hyperactivity disorder.
Treatment of PKU:
- If PKU is diagnosed early, an affected newborn can grow up with normal brain development, but only by managing and controlling phenylalanine levels through diet, or a combination of diet and medication.The diet requires severely restricting or eliminating foods high in phenylalanine, such as meat, chicken, fish, eggs, nuts, cheese, legumes, milk and other dairy products. Starchy foods, such as potatoes, bread, pasta, and corn, must be monitored.
- Optimal health ranges (or "target ranges") of serum phenylalanine are between 120 and 360 µmol/L, and aimed to be achieved during at least the first 10 years of life.
- Recently it has been found that a chiral isomer of L-phenylalanine (called D-phenylalanine) actually arrests the fibril formation by L-phenylalanine and gives rise to flakes. These flakes do not propagate further and prevent amyloid formation by L-phenylalanine. D-phenylalanine may qualify as a therapeutic molecule in phenylketonuria.
Phenylacetic Acid (PAA) is elevated:
- If the essential amino acid phenylalanine is not sufficiently digested and absorbed in the small intestine, it is carried to the large bowel where anaerobic bacteria convert it to phenylethylamine. This is then absorbed, and in body tissues such as the liver, it is converted by deamination to PAA, which is excreted in the urine.
- Some species of Clostridia can produce PAA directly from aromatic amino acids. Its presence at elevated levels indicates one or more of the following: gastric hypochlorhydria or pepsin inactivity, impaired digestive peptidase function in the small intestine, rate-limited or insufficient absorption or mucosal transport in the small intestine, abnormal intestinal motility (partly regulated by cholecystokinin and secretin), or presence of colonic or other bacteria in the small intestine (dysbiosis).
- Some elevation of PAA may occur in the uncommon instances of phenylketonuria and with Type I tyrosinemia (tyrosinosis). With phenylketonuria, 2-hydroxyphenylacetate (2-HPAA) would be significantly elevated. An amino acid analysis also is helpful in diagnosing such conditions.
- It is a white, powdery solid found in many foods and manufactured for food and drink products.
- Phenylalanine is highly concentrated in high protein foods, such as meat, cottage cheese, and wheat germ.
- Used in cocoa substitutes.
- Flavoring ingredient. A dietary source of phenylalanine is artificial sweeteners containing aspartame.
- Found naturally in the breast milk of mammal.
- An average adult ingests 5 g of phenylalanine per day and may optimally need up to 8 g daily.
- Sold as nutritional supplements for their reputed analgesic and antidepressant effects.
- Phenylalanine is better absorbed than tyrosine and may cause fewer headaches.
L-Phenylalanine Health Effects:
- L-Phenylalanine (LPA) is an electrically-neutral amino acid, one of the twenty common amino acids used to biochemically form proteins, coded for by DNA.
- Anti ADD
- Anti depressant
- Anti Parkinsonian
- Anti sickling
- Anti vitiligic
- Monoamine precursor
- L-phenylalanine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver.
- Phenylalanine hydroxylase converts phenylalanine to tyrosine.
- Normal metabolism of phenylalanine requires biopterin, iron, niacin, vitamin B6, copper and vitamin C.
- L-phenylalanine may be helpful in some with depression. The mechanism of L-phenylalanine putative antidepressant activity may be accounted for by its precursor role in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
- Phenylalanine can be an effective pain reliever.
- Its used in premenstrual syndrome and Parkinson's
- May enhance the effects of acupuncture and electric transcutaneous nerve stimulation (TENS).
- There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic drugs.
- It may also be useful in the treatment of vitiligo. The mechanism of L-phenylalanine possible anti vitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin.
- Low phenylalanine diets have been prescribed for certain cancers with mixed results. Some tumors use more phenylalanine (particularly melatonin-producing tumors called melanoma). One strategy is to exclude this amino acid from the diet, i.e., a Phenylketonuria (PKU) diet (compliance is a difficult issue; it is hard to quantify and is under-researched). The other strategy is just to increase phenylalanine competing for amino acids, i.e., tryptophan, valine, isoleucine, and leucine, but not tyrosine.
- High phenylalanine levels are particularly dangerous for children because it retards brain development and can cause serious learning difficulties.
- Chronically high levels of phenylalanine are associated with at least four other inborn errors of metabolism including:
- Hartnup Disorder, Hyperphenylalaninemia due to guanosine triphosphate cyclohydrolase deficiency, Tyrosinemia Type 2 (or Richner-Hanhart syndrome) and Tyrosinemia Type 3 (TYRO3).
Route of Exposure:
- Absorbed from the small intestine by a sodium-dependent active transport process.
- The psychotropic drugs (mescaline, morphine, codeine, and papaverine) also have phenylalanine as a constituent.