Alessandra F. Perna, 11First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Filomena Acanfora, 22First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Maria Grazia Luciano, 33First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Paola Pulzella, 44First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Rosanna Capasso, 55First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Ersilia Satta, 66First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Lombardi Cinzia, 77First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Rosa Maria Pollastro, 88First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Simona Iannelli, 99First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Diego Ingrosso, 1010Department of Biochemistry and Biophysics “F. Cedrangolo”, School of Medicine, Second University of Naples, Naples, Italy
Natale G. De Santo, 1111First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy
Corresponding author: Alessandra F. Perna, MD, PhD, Division of Nephrology/Department of Pediatrics, Second University of Naples, Via Pansini 5, Ed. 17, Naples, 80131 Italy Phone: +39-081-5666651, Fax: +39-081-5666655,
Citation Information. Clinical Chemical Laboratory Medicine. Volume 45, Issue 12, Pages 1678–1682, ISSN (Online) 14374331, ISSN (Print) 14346621, DOI: 10.1515/CCLM.2007.336, December 2007
Publication History: Received: 19/6/2007; accepted: 10/8/2007; published online: 08/12/2007
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.
Clin Chem Lab Med 2007;45:1678–82.
Keywords albumin, folate, hemodialysis, homocysteine, protein homocysteinylation, uremia
