Current Landscape on Development of Phenylalanine and Toxicity of its Metabolites - A Review

Abstract

Phenylalanine, an essential amino acid, is the "building block" of protein. It has a tremendous role in different aspects of metabolic events. The tyrosine pathway is the prime one and is typically used to degrade dietary phenylalanine. Phenylalanine exceeds its limit in bodily fluids and the brain when the enzyme, phenylalanine decarboxylase, phenylalanine transaminase, phenylalanine hydroxylase (PAH) or its cofactor tetrahydrobiopterin (BH4) is deficient causes phenylketonuria, schizophrenia, attention-deficit/hyperactivity disorder and another neuronal effect. Tyrosine, an amino acid necessary for synthesizing the pigments in melanin, is produced by its primary metabolic pathway. Deficiency/abnormality in metabolic enzymes responsible for the catabolism pathway of Phenylalanine causes an accumulation of the active intermediate metabolite, resulting in several abnormalities, such as developmental delay, tyrosinemias, alkaptonuria, albinism, hypotension and several other undesirable conditions. Dietary restriction of the amino acid(s) can be a therapeutic approach to avoid such undesirable conditions when the level of metabolic enzyme is unpredictable. After properly identifying the enzymatic level, specific pathophysiological conditions can be managed more efficiently.

Early versus late parenteral nutrition in term and late preterm infants: a randomised controlled trial

“…23 27 28 Experimental studies have shown that hyperphenylalaninaemia can induce oxidative stress, inflammation, mitochondrial dysfunction and neuronal apoptosis. [29][30][31][32][33] Hence, it is important to weigh the risks and benefits of commencing PN very early in the neonatal period.…”