title: In vivo investigation of homocysteine metabolism to polyamines by high-resolution accurate mass spectrometry and stable isotope labeling.
abstract: Polyamines are essential polycations, playing important roles in mammalian physiology. Theoretically, the involvement of homocysteine in polyamine synthesis via S-adenosylmethionine is possible; however, to our knowledge, it has not been established experimentally. Here, we propose an original approach for investigation of homocysteine metabolites in an animal model. The method is based on the combination of isotope-labeled homocysteine supplementation and high-resolution accurate mass spectrometry analysis. Structural identity of the isotope-labeled metabolites was confirmed by accurate mass measurements of molecular and fragment ions and comparison of the retention times and tandem mass spectrometry fragmentation patterns. Isotope-labeled methionine, spermidine, and spermine were detected in all investigated plasma and tissue samples. The induction of moderate hyperhomocysteinemia leads to an alteration in polyamine levels in a different manner. The involvement of homocysteine in polyamine synthesis and modulation of polyamine levels could contribute to a better understanding of the mechanisms connected with homocysteine toxicity.
authors.affiliation: Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1431, Bulgaria.
authors.forename: Silviya
authors.initials: S
authors.lastname: Ruseva
authors.affiliation: Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1431, Bulgaria. Electronic address: bovalv@gmail.com.
authors.forename: Valentin
authors.initials: V
authors.lastname: Lozanov
authors.affiliation: Department of Physiology, Medical University of Sofia, Sofia 1431, Bulgaria.
authors.forename: Petia
authors.initials: P
authors.lastname: Markova
authors.affiliation: Department of Physiology, Medical University of Sofia, Sofia 1431, Bulgaria.
authors.forename: Radoslav
authors.initials: R
authors.lastname: Girchev
authors.affiliation: Department of Medical Chemistry and Biochemistry, Medical University of Sofia, Sofia 1431, Bulgaria.
authors.forename: Vanio
authors.initials: V
authors.lastname: Mitev
mesh_terms: D000818:Animals; D006710:Homocysteine / Q000737:chemistry* / Q000378:metabolism*; D007553:Isotope Labeling; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013095:Spermidine / Q000096:biosynthesis; D013096:Spermine / Q000096:biosynthesis
chemical_list: D006710:Homocysteine; D013096:Spermine; D013095:Spermidine
keywords: Homocysteine; Mass spectrometry; Metabolism; Orbitrap; Spermidine; Spermine