Examining the blood amino acid status in pretherapeutic patients with  hyperphenylalaninemia

Abstract

Background Hyperphenylalaninemia is the most common genetic metabolic disease. Early treatment prevents brain injury effectively. The present study aimed to detect the exact amino acid status of patients with hyperphenylalaninemia before treatment. Methods Data of 116 newborn patients from our Newborn Screening Center and 161 older patients from our clinic before treatment were collected. The content of 17 amino acids in their blood was determined by tandem mass spectrometry and compared with normal controls. Relationship between phenylalanine and other amino acids in patients was analyzed using the smoothing curve fitting and threshold effect analysis. Results Most amino acids in the blood of patients were within the normal range; however, they were different significantly from those of the normal children. Newborn patients showed higher phenylalanine (346.30 vs 45.90 µmol/L), valine (121.50 vs 110.30 µmol/L), citrulline, ornithine and lower tyrosine (52.97 vs 66.12 µmol/L), threonine (68.68 vs 78.21 µmol/L), glutamine levels than observed in normal newborns. Older patients showed significantly higher phenylalanine (844.00 vs 51.82 µmol/L), valine (117.60 vs 110.90 µmol/L), histidine, serine and lower tyrosine (55.97 vs 67.31 µmol/L), threonine (35.94 vs 51.89 µmol/L), alanine, asparagine, glutamic acid, methionine, arginine, glycine, ornithine, glutamine content than found in matched normal children. Tyrosine, valine, ornithine, and threonine in newborn patients and tyrosine, glycine, glutamine, and threonine in older patients had a nonlinear correlation with phenylalanine levels with obvious threshold effect and clear inflection points. Conclusion Significant difference was observed in the amino acid status between pretherapeutic hyperphenylalaninemia patients and normal children. Some amino acids showed notable threshold effect with phenylalanine level in a nonlinear pattern.

Changes in Amino Acid Pool in Rats with Brain Ischemia

“…As is known, one of the directions for detailing the mechanisms of development of damage and adaptation of the brain during its ischemia is the study of changes in the pool of amino acids [1,2]. Amino acids and their derivatives play an important role in the functioning of the brain, both in normal and pathological conditions, participating in the biosynthesis of membrane and signal protein and peptide molecules, some lipids, vitamins, hormones, and biogenic amines, and are also directly involved in the implementation of neurotransmitter functions, regulation of the activity of excitation and inhibition processes (glutamate, aspartate, GABA) [3][4][5][6]. Aromatic amino acids (phenylalanine, tyrosine, tryptophan, histidine) are of particular importance as precursors of catecholamines and serotonin [7,8].…”

Distribution of the Pool of Amino Acids in The Parietal Lobe of Albino Rats

“…The main metabolic pathway of this amino acid in the body is hydroxylation to tyrosine with the participation of the enzyme phenylalanine-4-hydroxylase, followed by the formation of the main catecholamine precursor dihydroxyphenylalanine (DOPA). With an enzyme deficiency observed in phenylketonuria, the conversion of phenylalanine occurs along the path of formation of phenylpyruvic and phenylacetic acids, which have a toxic effect on the brain[2,14].Tyrosine acts as a source of catecholamines in the brain. The conversion of tyrosine to catecholamines is the leading pathway for the metabolism of tyrosine in the brain.…”