Uptake and metabolism of N-(4'-pyridoxyl)amines by isolated rat liver cells.
Uptake and metabolism of [3H]pyridoxine and 3H-labeled N-(4'-pyridoxyl)amines by isolated rat liver cells were studied at physiological concentration (0.5 microM) of vitamin B6 by using both membrane filtration and centrifugation methods for removal of radiolabeled solutes after incubations with cells. It was found that the characteristics of import of N-(4'-pyridoxyl)amines into liver cells is similar to those of import of natural vitamin B6. Upon entry each 4'(N)-substituted pyridoxamine was converted to its 5'-phosphate and then oxidized to release pyridoxal 5'-phosphate and the original amine. Considerable size of the amine substituent is tolerated for transport and metabolism, but a charged function impedes entry. The amount of released pyridoxal 5'-phosphate (and therefore the amount of released original amine) is controlled partially by the size of the amine affixed to B6 and partially by the enzymatic steps involved. This system illustrates how biologically active amines can be piggybacked onto a vitamin that gains facilitated entry to cells that have the enzymatic means to release the free amine for subsequent effects within the cell.
Zhang
Z
Z
Department of Biochemistry, Emory University, Atlanta, Georgia 30322.
McCormick
D B
DB
D000818:Animals; D001692:Biological Transport; D001711:Biotransformation; D002478:Cells, Cultured; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011732:Pyridoxal Phosphate / Q000378:metabolism; D011733:Pyridoxamine / Q000031:analogs & derivatives* / Q000378:metabolism*; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D014316:Tritium
D014316:Tritium; D011732:Pyridoxal Phosphate; D011733:Pyridoxamine; D011736:Pyridoxine