title: Investigation of Fibril Forming Mechanisms of l-Phenylalanine and l-Tyrosine: Microscopic Insight toward Phenylketonuria and Tyrosinemia Type II.
abstract: Phenylketonuria and tyrosinemia type II, the two metabolic disorders, are originated due to the complications in metabolism of phenylalanine (Phe) and tyrosine (Tyr), respectively. Several neurological injuries, involving microcephaly, mental retardation, epilepsy, motor disease, and skin problems etc., are the symptoms of these two diseases. It has been reported that toxic amyloid fibrils are formed at high concentrations of Phe and Tyr. Our study indicates that the fibril forming mechanisms of Phe and Tyr are completely different. In the case of Phe, -NH3+and -COO-groups of neighboring molecules interact via hydrogen bonding and polar interactions. On the other hand, there is no role of - NH3+group in the fibril forming mechanism of Tyr. In Tyr fibril, the two hydrogen bonding partners are -OH and -COO-groups. In addition, we have also investigated the effect of three lanthanide cations on the fibrillar assemblies of Phe. It has been observed that the efficiencies of three lanthanides to inhibit the fibrillar assemblies of Phe follow the order Tb3+< Sm3+< Eu3+.
authors.affiliation: Department of Chemistry, Indian Institute of Technology , Kharagpur 721302, WB, India.
authors.forename: Debasis
authors.initials: D
authors.lastname: Banik
authors.affiliation: Department of Chemistry, Indian Institute of Technology , Kharagpur 721302, WB, India.
authors.forename: Sangita
authors.initials: S
authors.lastname: Kundu
authors.affiliation: Department of Chemistry, Indian Institute of Technology , Kharagpur 721302, WB, India.
authors.forename: Pavel
authors.initials: P
authors.lastname: Banerjee
authors.affiliation: Department of Chemistry, Indian Institute of Technology , Kharagpur 721302, WB, India.
authors.forename: Rupam
authors.initials: R
authors.lastname: Dutta
authors.affiliation: Department of Chemistry, Indian Institute of Technology , Kharagpur 721302, WB, India.
authors.forename: Nilmoni
authors.identifier: 0000-0002-8714-0000
authors.initials: N
authors.lastname: Sarkar
mesh_terms: D043844:Crown Ethers / Q000737:chemistry; D005063:Europium / Q000737:chemistry; D006860:Hydrogen Bonding; D007700:Kinetics; D046911:Macromolecular Substances / Q000737:chemistry*; D010649:Phenylalanine / Q000737:chemistry*; D010661:Phenylketonurias / Q000503:physiopathology; D012493:Samarium / Q000737:chemistry; D013725:Terbium / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry*; D020176:Tyrosinemias / Q000503:physiopathology
chemical_list: D043844:Crown Ethers; D046911:Macromolecular Substances; D013725:Terbium; D014443:Tyrosine; D012493:Samarium; D005063:Europium; D010649:Phenylalanine; C015762:18-crown-6