title: In-silico and in-vitro investigation on the phenylalanine metabolites' interactions with hexokinase of Rat's brain mitochondria.
abstract: Hexokinase (HK) is the first enzyme of glycolysis pathway. In brain, most dominant form of HK, HK-I, binds reversibly to the outer mitochondria membrane. Those metabolites that affect binding or releasing of the enzyme from the mitochondria have regulatory effect on glucose consumption of the cell. In this study destructive effect of phenylalanine and its metabolites in relation to glucose metabolism in brain have been studied. The results show that phenylpyruvic acid decreases the activity of enzyme in the presence and absence of glucose-6-phosphate (G6P) and increases the release of the enzyme from mitochondria, whereas phenylalanine and phenyllactic acid have no such effects. Obtained Interactions and elicited binding energies of docking and MD simulations also showed more affinity for phenylpyruvic acid compared with the other potent inhibitors for hexokinase after the natural product of G6P. It is possible that phenylpyruvic acid is the cause of the reduction of glucose consumption by decreasing hexokinase activity and the higher inhibitory function. Therefore, production of ATP declines in brain cells.
authors.affiliation: Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran. n.ziamajidi@umsha.ac.ir.
authors.forename: Nasrin
authors.identifier: http://orcid.org/0000-0002-7473-9823
authors.initials: N
authors.lastname: Ziamajidi
authors.affiliation: School of Medicine, Shahid Beheshti University of Medical Sciences and Health services, Tehran, Iran.
authors.forename: Shirin
authors.initials: S
authors.lastname: Jamshidi
authors.affiliation: Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Abdolvahab
authors.initials: A
authors.lastname: Ehsani-Zonouz
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006593:Hexokinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008928:Mitochondria; D062105:Molecular Docking Simulation; D010649:Phenylalanine / Q000378:metabolism*; D010667:Phenylpyruvic Acids; D011485:Protein Binding; D051381:Rats
chemical_list: D010667:Phenylpyruvic Acids; D010649:Phenylalanine; D006593:Hexokinase; D005947:Glucose; C031606:phenylpyruvic acid
keywords: Hexokinase; Molecular docking; Molecular dynamics simulation; Phenylalanine; Phenyllactic acid; Phenylpyruvic acid