Increased serum phenylalanine concentration in a newborn is primarily a result of a defect in which metabolic process?

• A. Transport of tyrosine
• B. Metabolism of tetrahydrobiopterin
• C. Transport of branched-chain amino acids
• D. Transport of phenylalanine across enterocytes

Answer: (B)

Increased serum phenylalanine concentration in a newborn is primarily associated with a defect in the metabolism of tetrahydrobiopterin (BH4). This cofactor is essential in the hydroxylation reactions that convert phenylalanine to tyrosine, a critical step in the catabolic pathway of phenylalanine. When there is a deficiency in BH4, such as in some forms of phenylketonuria (PKU), phenylalanine cannot be effectively metabolized, leading to its accumulation in the serum.

This buildup is problematic because it can result in neurological damage and developmental issues if not managed correctly. While transport deficiencies may contribute to abnormal amino acid levels, the fundamental issue leading to elevated phenylalanine in this scenario is the impaired metabolic process involving BH4, which is crucial for the enzymatic conversion of phenylalanine into the downstream product, tyrosine. Therefore, the identification of a defect in the metabolism of tetrahydrobiopterin directly correlates with the pathophysiology of increased serum phenylalanine levels in newborns.