What Is Phenylalanine? Other Names: Acide Isovalérique de Phénylalanine, DLPA, Fenilalanina

What is Phenylalanine?

This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. Phenylalanine is an essential aromatic amino acid that plays a crucial role in various physiological processes. It is a precursor for several important biomolecules and is vital for normal growth and development. This article explores the significance of phenylalanine, its dietary requirements, and its impact on health. Other names include: 2-amino-3-phenyl-propanoic acid, Acide Alpha-aminohydrocinnamique, Acide Isovalérique de Phénylalanine, Alpha-aminohydrocinnamic Acid, Beta-phenyl-alanine, Bêta-phenyl-alanine, DLPA, D-Phenylalanine, D-Phénylalanine, DL-Phenylalanine, DL-Phénylalanine, D,L-Phenylalanine, D,L-Phénylalanine, Fenilalanina, L-Phenylalanine, L-Phénylalanine, Phenylalanine Ethyl Ester HCl, Phenylalanine Isovaleric Acid, Phenylalanine Methyl Ester HCl.

Phenylalanine Dietary Requirements

Phenylalanine is essential for protein synthesis and must be obtained through the diet. The dietary requirements for phenylalanine vary across different age groups and physiological conditions.

Elderly Adults

A study determined that the phenylalanine requirement for elderly adults is similar to that of young adults. The mean requirement was found to be 9.03 mg/kg/day, with an upper 95% confidence interval of 15.9 mg/kg/day, suggesting that the higher protein needs of the elderly are not driven by an increased requirement for phenylalanine.

Neonates

For neonates, especially those who are preterm, the phenylalanine requirement is higher. Term neonates require a minimum of 58 mg/kg/day, while preterm neonates need about 80 mg/kg/day. These requirements are crucial for optimal growth and development.

Healthy Adults

In healthy Indian adults, the phenylalanine requirement was estimated to be around 38 mg/kg/day in the absence of tyrosine intake. This finding aligns with the requirements observed in Western adults.

Physiological Roles of Phenylalanine

Phenylalanine is not only important for protein synthesis but also plays a role in the synthesis of other critical molecules.

Protein Synthesis and Tyrosine Conversion

Phenylalanine can be hydroxylated to form tyrosine, another essential amino acid. This conversion is vital for the synthesis of neurotransmitters such as dopamine, norepinephrine, and epinephrine, which are crucial for brain function and mood regulation.

Impact on Cognitive Function

In patients with phenylketonuria (PKU), a condition where phenylalanine cannot be properly metabolized, maintaining appropriate phenylalanine levels is critical. Elevated phenylalanine levels can impact cognitive function and brain structure. A study on adults with early-treated PKU showed that temporarily elevated phenylalanine levels could influence cognitive performance and cerebral parameters.

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Health Implications of Phenylalanine

Phenylalanine has several health implications, particularly in metabolic and gastrointestinal functions.

Appetite Regulation and Glycemic Control

Phenylalanine stimulates the release of cholecystokinin (CCK) and peptide-YY (PYY), hormones that regulate appetite and energy intake. It also influences glycemic control by stimulating insulin and glucagon release, although it does not affect gastric emptying.

Exercise and Fat Oxidation

Supplementation with phenylalanine before exercise has been shown to increase fat oxidation. This effect is likely due to the stimulation of glucagon secretion, which promotes fat mobilization during physical activity.

Pancreatic Development

In milk-fed Holstein calves, phenylalanine supplementation influenced pancreatic development and enzyme activity. It increased the concentration of plasma insulin and cholecystokinin, which are important for digestive processes.

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Adverse Effects of Phenylalanine

Neuropsychological and Mood Effects

High phenylalanine levels can impair sustained attention and negatively affect mood in adults with PKU .

Bone Health

Elevated plasma phenylalanine concentrations may adversely affect bone status, leading to reduced femur weight and length, and potentially higher bone turnover in PKU mice.

Body Weight and Food Consumption

High dietary intake of phenylalanine can lead to reduced body weight and food consumption, indicating mild toxicity at higher doses.

Gastrointestinal and Hormonal Effects

Phenylalanine stimulates the release of gastrointestinal hormones like cholecystokinin (CCK) and peptide-YY (PYY), which can suppress energy intake and affect glycaemic responses .

High doses of phenylalanine can cause nausea, which may influence food intake.

Metabolic and Glucoregulatory Effects

Phenylalanine can stimulate insulin and glucagon release, affecting blood glucose levels .

Mortality and Organ Weight in Animals

In broilers, phenylalanine supplementation in the presence of ochratoxin A (OA) reduced mortality and affected relative organ weights, indicating potential protective effects against OA toxicity.

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How has Phenylalanine Improved Patient Outcomes?

Breast Cancer Treatment

L-phenylalanine mustard (L-PAM) as an adjuvant to mastectomy significantly improves disease-free survival in premenopausal breast cancer patients, particularly those under 49 years old and those with fewer positive axillary nodes .

Phenylketonuria (PKU) Management

Phenylalanine-free amino acid supplementation in untreated PKU patients improves concentration, awareness, and reduces self-injury, leading to better adaptive behavior.

Sapropterin (BH4), a synthetic form of tetrahydrobiopterin, significantly reduces blood phenylalanine levels in PKU patients, potentially allowing for less restrictive diets .

Elevated phenylalanine levels negatively impact mood and sustained attention in adults with PKU, suggesting the importance of maintaining a Phe-restricted diet.

Multiple Sclerosis

Combination therapy with L-phenylalanine, lofepramine, and vitamin B-12 shows a small but significant improvement in disability scores in multiple sclerosis patients.

Attention Deficit Disorder

DL-phenylalanine shows initial improvement in mood and mood lability in adults with attention deficit disorder, though benefits are not sustained long-term.

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Phenylalanine Mechanisms of Action

Stimulation of Satiety Hormones and Appetite Regulation

Phenylalanine stimulates the release of cholecystokinin (CCK) and peptide-YY (PYY), which are hormones involved in promoting satiety and reducing energy intake .

The suppression of energy intake by phenylalanine is correlated with the stimulation of CCK and PYY .

Glucoregulatory Effects

Phenylalanine increases the secretion of insulin and glucagon, which are key hormones in glucose metabolism .

It reduces overall and peak plasma glucose levels in response to a mixed-nutrient drink, indicating a role in blood glucose regulation.

Fat Oxidation During Exercise

Phenylalanine supplementation before exercise increases plasma glycerol and glucagon levels, promoting fat oxidation.

Pancreatic Development and Enzyme Activity

In animal studies, phenylalanine supplementation increases plasma insulin and cholecystokinin levels, and affects pancreatic DNA concentration and trypsin gene expression.

Neurological and Cognitive Effects

Elevated phenylalanine levels can influence cognitive performance and brain function, particularly in individuals with phenylketonuria (PKU).

Phenylalanine may activate the noradrenergic locus coeruleus/lateral tegmentum (LC/LT) system, potentially affecting brain and spinal cord function.

Competitive Transport Across the Blood-Brain Barrier

Phenylalanine competes with other large neutral amino acids (LNAA) for transport across the blood-brain barrier, which can be leveraged to lower brain phenylalanine levels in PKU treatment.

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Common Complaints Associated with Phenylalanine Use

Mood and Cognitive Function

High plasma Phe levels negatively impact mood and sustained attention in adults with PKU.

Discontinuation of a Phe-restricted diet in PKU patients is associated with increased rates of mental disorders and lower intellectual and achievement test scores.

Medical and Behavioral Problems

Patients who do not adhere to a Phe-restricted diet report higher incidences of eczema, asthma, headaches, hyperactivity, and hypoactivity.

Gastrointestinal Issues

Adverse events related to Phe use, particularly in the context of engineered bacterial treatments, are mostly gastrointestinal and of mild to moderate severity.

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