Pyridoxal phosphate annuls acetaldehyde inhibition of uridine uptake by hepatocytes

Methods were evaluated for depressing the acetaldehyde (AcH) inhibition of uridine uptake by Chang liver cells and isolated autologous liver cells, obtained by percutaneous liver biopsy from cases of alcoholic hepatitis. Hepatocytes so obtained were significantly more susceptible to AcH-induced inhibition of uridine uptake than hepatocytes from normal liver, alcoholic fatty liver, stable alcoholic cirrhosis and acute viral hepatitis. Benzylamine (an aldehyde buffer) and pyridoxal-5' phosphate (PLP) counteracted the inhibition of uridine uptake by AcH in vitro. We suggest that benzylamine neutralizes AcH toxicity through a Schiff-base condensation with AcH thus taking AcH out of the field of action. PLP protects against AcH-induced inhibition of uridine uptake by probably forming a Schiff base with cellular amino acids thus blocking further condensation of these amino groups with AcH. In this manner, uridine uptake by liver cells for RNA synthesis can proceed without interference by AcH.