Dysregulated Choline, Methionine, and Aromatic Amino Acid Metabolism in Patients with Wilson Disease: Exploratory Metabolomic Profiling and Implications for Hepatic and Neurologic Phenotypes.

Wilson disease (WD) is a genetic copper overload condition characterized by hepatic and neuropsychiatric symptoms with a not well-understood pathogenesis. Dysregulated methionine cycle is reported in animal models of WD, though not verified in humans. Choline is essential for lipid and methionine metabolism. Defects in neurotransmitters as acetylcholine, and biogenic amines are reported in WD; however, less is known about their circulating precursors. We aimed to study choline, methionine, aromatic amino acids, and phospholipids in serum of WD subjects. Hydrophilic interaction chromatography-quadrupole time-of-flight mass spectrometry was employed to profile serum of WD subjects categorized as hepatic, neurologic, and pre-clinical. Hepatic transcript levels of genes related to choline and methionine metabolism were verified in the Jackson Laboratory toxic milk mouse model of WD (tx-j). Compared to healthy subjects, choline, methionine, ornithine, proline, phenylalanine, tyrosine, and histidine were significantly elevated in WD, with marked alterations in phosphatidylcholines and reductions in sphingosine-1-phosphate, sphingomyelins, and acylcarnitines. In tx-j mice, choline, methionine, and phosphatidylcholine were similarly dysregulated. Elevated choline is a hallmark dysregulation in WD interconnected with alterations in methionine and phospholipid metabolism, which are relevant to hepatic steatosis. The elevated phenylalanine, tyrosine, and histidine carry implications for neurologic manifestations and are worth further investigation

Local atomic arrangement and martensitic transformation in Ni50_{50}Mn35_{35}In15_{15}: An EXAFS Study

Heusler alloys that undergo martensitic transformation in ferromagnetic state are of increasing scientific and technological interest. These alloys show large magnetic field induced strains upon martensitic phase change thus making it a potential candidate for magneto-mechanical actuation. The crystal structure of martensite is an important factor that affects both the magnetic anisotropy and mechanical properties of such materials. Moreover, the local chemical arrangement of constituent atoms is vital in determining the overall physical properties. Ni$_{50}$Mn$_{35}$In$_{15}$ is one such ferromagnetic shape memory alloy that displays exotic properties like large magnetoresistance at moderate field values. In this work, we present the extended x-ray absorption fine-structure measurements (EXAFS) on the bulk Ni$_{50}$Mn$_{35}$In$_{15}$ which reveal the local structural change that occurs upon phase transformation. The change in the bond lengths between different atomic species helps in understanding the type of hybridization which is an important factor in driving such Ni-Mn based systems towards martensitic transformation