Plasma protein homocysteinylation in uremia.
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.
Perna
Alessandra F
AF
First Division of Nephrology, School of Medicine, Second University of Naples, Naples, Italy. alessandra.perna@unina2.it
Acanfora
Filomena
F
Luciano
Maria Grazia
MG
Pulzella
Paola
P
Capasso
Rosanna
R
Satta
Ersilia
E
Cinzia
Lombardi
L
Pollastro
Rosa Maria
RM
Iannelli
Simona
S
Ingrosso
Diego
D
De Santo
Natale G
NG
D001798:Blood Proteins / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D006435:Renal Dialysis; D014511:Uremia / Q000097:blood / Q000378:metabolism*
D001798:Blood Proteins; D006710:Homocysteine