The Phenylalanine/Tyrosine Ratio evaluates the body’s ability to convert phenylalanine to tyrosine; Conversion enzyme requires tetrahydrobiopterin (BH4), niacin (B3), and iron as cofactors.
Elevations in the serum Phenylalanine/Tyrosine Ratio have potential value for estimating the presence of an inflammatory disease and the catabolic state of a person.
This marker is also routinely used to screen newborns for phenylketonuria, an inborn error of metabolism that results in decreased metabolism of phenylalanine. This results in the buildup of dietary phenylalanine to potentially toxic levels. Not sufficient, because other causes of hyperphenylalaninemia (eg, BH4 deficiency) cannot be excluded by this test alone.
Phenylalanine is one of the amino acids, which are important nutrients that we get from our diets. Amino acids are used by the body to make protein which is essential for most physiological processes. Amino acids also serve as precursors to be converted by enzymes into other important compounds for the brain and other organs.
The metabolic pathway here is the conversion of phenylalanine into tyrosine. The importance of this pathway is that it removes excess phenylalanine and it enables the production of sufficient tyrosine. Tyrosine is important for the production of neurotransmitters that function in the brain. The enzyme phenylalanine hydroxylase (PAH) is responsible for enabling the phenylalanine to tyrosine conversion to take place.
Individuals with phenylketonuria have a genetic defect in the ability to produce PAH, therefore the phenylalanine they get from their diet keeps accumulating rather than being converted to tyrosine. The two major consequences are: (1) toxic levels of phenylalanine in the body and (2) high ratio of phenylalanine to tyrosine associated with impairment of the production of neurotransmitters.
High levels of phenylalanine, as seen in untreated phenylketonuria, cause brain damage and associated mental retardation. Early implementation of a low phenylalanine diet prevents the mental retardation associated with this condition.
References:
-https://www.jstor.org/stable/3654370
-https://www.hindawi.com/journals/jaa/2014/783730/
-https://www.ncbi.nlm.nih.gov/pubmed/18701209
-https://www.ncbi.nlm.nih.gov/pubmed/822705
-https://content.iospress.com/articles/journal-of-parkinsons-disease/jpd150736
-https://www.hindawi.com/journals/jaa/2014/783730/
-https://onlinelibrary.wiley.com/doi/pdf/10.1111/1467-8624.00370
Increased levels can potentially be used to diagnose phenylketonuria. If no inborn errors of metabolism (i.e. phenylketonuria) are present: Infections or inflammatory states often cause significant increases in serum phenylalanine and the phenylalanine-tyrosine ratio.
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1-Methylhistidine (Plasma), 3-Methylhistidine (Plasma), Alanine (Plasma), Alpha-Amino-n-butyric acid (Plasma), Alpha-Aminoadipic Acid (Plasma), Alpha-ANB/Leucine, Anserine (Plasma), Arginine (Plasma), Asparagine (Plasma), Aspartic Acid (Plasma), Beta-Alanine, Beta-Aminoisobutyric Acid (Plasma), Carnosine (Plasma), Citrulline, Cystathionine (Plasma), Cystine, Ethanolamine (Plasma), g-Aminobutyric Acid (Plasma), Glutamic Acid (Plasma), Glutamic Acid/Glutamine, Glutamine (Plasma), Glycine (Plasma), Histidine (Plasma), Homocysteine (Genova), Homocystine (Genova), Hydroxylysine (Genova), Hydroxyproline (Genova), Hydroxyproline/Proline (Genova), Isoleucine (Plasma), Leucine (Plasma), Lysine (Plasma), Methionine (Plasma), Ornithine (Genova), Phenylalanine (Plasma), Phenylalanine/Tyrosine (Genova), Phosphoethanolamine (Plasma), Phosphoserine (Plasma), Proline (Plasma), Sarcosine (Plasma), Serine (Plasma), Taurine (Plasma), Threonine (Plasma), Tryptophan (Plasma), Tryptophan/LNAA (Genova), Tyrosine (Plasma), Valine (Plasma)
