Mechanism of erythrocyte accumulation of methylation inhibitor S-adenosylhomocysteine in uremia

• Published in: Kidney international Vol. 47; no. 1; pp. 247 - 253
• Main Authors: Perna, Alessandra F., Ingrosso, Diego, De Santo, Natale G., Galletti, Patrizia, Zappia, Vincenzo
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 01.01.1995; Nature Publishing
• Subjects: Adenosine - analysis; Adenosylhomocysteinase; Adult; Aspartate Aminotransferases - analysis; Biological and medical sciences; Erythrocytes - chemistry; Erythrocytes - metabolism; Female; Homocysteine - metabolism; Humans; Hydrolases - analysis; Male; Medical sciences; Methylation - drug effects; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Renal failure; S-Adenosylhomocysteine - metabolism; S-Adenosylhomocysteine - pharmacology; S-Adenosylmethionine - analysis; Uremia - blood; Human; Adenosine; Purine nucleoside; Thiol; Urinary system disease; Pathophysiology; Enzyme; Transferases; Red blood cell; Enzyme inhibitor; Renal disease; Thioether hydrolases; Exploration; Blood plasma; Sulfur containing aminoacid; Chronic; Enzymatic activity; Methyltransferases; Adenosylhomocysteinase; Renal failure; Hydrolases; Intracellular
• ISSN: 0085-2538; 1523-1755
• DOI: 10.1038/ki.1995.31

Mechanism of erythrocyte accumulation of methylation inhibitor S-adenosylhomocysteine in uremia. We have recently demonstrated that methyl esterification of erythrocyte membrane proteins, a reaction involved in recognition and repair of specifically damaged proteins, is impaired in uremia. This is accompanied by a significant increase in intracellular S-adenosylhomocysteine (AdoHcy), a potent inhibitor of methyltransferases. AdoHcy accumulation is normally prevented by its enzymatic hydrolysis to homocysteine (Hey) and adenosine, a reversible reaction catalyzed by AdoHcy hydrolase. To assess the contribution that Hey offers in the elevation of AdoHcy, we measured plasma and red blood cell Hey, AdoHcy, adenosine, and S-adenosylmethionine (AdoMet) intracellular concentrations, as well as RBC AdoHcy hydrolase specific activity, in standard hemodialysis patients and normal subjects. Plasma and red blood cell Hey levels are significantly higher in the dialysis group, and are positively correlated to AdoHcy levels. Adenosine and AdoMet levels, and AdoHcy hydrolase specific activity are not significantly different between the two groups. The enzymatic formation of labeled AdoHcy from Hey and tracer adenosine appears to be significantly increased, in vitro, in erythrocytes from both control and uremic patients, when 50 µM Hey (concentration comparable to plasma levels actually found in vivo in uremic patients) is added to the incubation medium. When erythrocytes from uremic patients are incubated in vitro in absence of Hey, a significant reduction of intracellular AdoHcy is observed with time compared to identical samples incubated in presence of 50 µM Hey, with a T1/2 of approximately 270 minutes. The results allow us to conclude that plasma and red cell Hey levels actually found in uremia can be effectively responsible for the intracellular accumulation of the toxic compound AdoHcy.