Structural and Evolutionary Analysis of Disease-Associated Missense Variants in Phenylalanine Hydroxylase

Shaurya Chandna

Abstract: Phenylalanine Hydroxylase (PAH) is a critical enzyme found in the liver that catalyses the bioconversion of the dietary amino acid phenylalanine into the nonessential amino acid tyrosine (Scriver et al., 2001; Blau et al., 2010). This bioconversion is considered to be an important regulatory step in amino acid metabolism and is necessary for the maintenance of physiological levels of phenylalanine in the body. PAH belongs to the class of aromatic amino acid hydroxylases (AAAH) and acts as a monooxygenase that utilises molecular oxygen (O?), ferrous iron (Fe??), and tetrahydrobiopterin (BH?) as cofactors for its enzymatic activity (Fitzpatrick, 2012). Disruption of this tightly regulated enzymatic/biochemical pathway results in the accumulation of phenylalanine (Phe), a toxic substance to both the developing and fully developed nervous system (Scriver et al., 2001).

Keywords: phenylalanine metabolism, liver enzyme function, tyrosine formation, amino acid balance, nervous system toxicity

How to Cite?: Shaurya Chandna, "Structural and Evolutionary Analysis of Disease-Associated Missense Variants in Phenylalanine Hydroxylase", Volume 15 Issue 2, February 2026, International Journal of Science and Research (IJSR), Pages: 318-326, https://www.ijsr.net/getabstract.php?paperid=SR26205050735, DOI: https://dx.doi.org/10.21275/SR26205050735