title: Plasma protein homocysteinylation in uremia.
abstract: Protein homocysteinylation is proposed as one of the mechanisms of homocysteine toxicity. It occurs through various means, such as the post-biosynthetic acylation of free amino groups (protein-N-homocysteinylation, mediated by homocysteine thiolactone) and the formation of a covalent -S-S- bond found primarily with cysteine residues (protein-S-homocysteinylation). Both protein modifications are a cause of protein functional derangements. Hemodialysis patients in the majority of cases are hyperhomocysteinemic, if not malnourished. Protein-N-homocysteinylation and protein-S-homocysteinylation are significantly increased in hemodialysis patients compared to controls. Oral folate treatment normalizes protein-N-homocysteinylation levels, while protein-S-homocysteinylation is significantly reduced. Albumin binding experiments after in vitro homocysteinylation show that homocysteinylated albumin is significantly altered at the diazepam, but not at the warfarin and salicilic acid binding sites.
authors.affiliation: First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy. alessandra.perna@unina2.it
authors.forename: Alessandra F
authors.initials: AF
authors.lastname: Perna
authors.forename: Filomena
authors.initials: F
authors.lastname: Acanfora
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Luciano
authors.forename: Paola
authors.initials: P
authors.lastname: Pulzella
authors.forename: Rosanna
authors.initials: R
authors.lastname: Capasso
authors.forename: Ersilia
authors.initials: E
authors.lastname: Satta
authors.forename: Lombardi
authors.initials: L
authors.lastname: Cinzia
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Pollastro
authors.forename: Simona
authors.initials: S
authors.lastname: Iannelli
authors.forename: Diego
authors.initials: D
authors.lastname: Ingrosso
authors.forename: Natale G
authors.initials: NG
authors.lastname: De Santo
mesh_terms: D001798:Blood Proteins / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood / Q000378:metabolism*
chemical_list: D001798:Blood Proteins; D006710:Homocysteine