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Clinical Studies (Return to Clinical
Studies page)
VITAMIN B-6 (PYRIDOXINE HCL)
ESSENTIAL FOR HEMOGLOBIN SYNTHESIS
Ink SL, Mehansho H, Henderson
LM. (1982). The binding of pyridoxal to hemoglobin. J Biol Chem. 257(9):4753-7.
Concentrative uptake of
pyridoxal by human erythrocytes has been investigated using a rapid mixing technique with
3H-labeled pyridoxal. A nonsaturable, initial influx of 3H pyridoxal into the erythrocyte
indicated passive diffusion. Since pyridoxal will form Schiff bases reversibly with amino acids,
the possibility of binding to intracellular proteins was examined. Exposure of erythrocytes to
pyridoxal followed by NaBH4 reduction, resulted in a stable pyridoxyl-protein complex. The
binding site for pyridoxal was found to be on the alpha chain of oxyhemoglobin, as determined by
ion exchange chromatography and amino acid analysis. Separation of the tryptic peptides from the
[3H]pyridoxyl-alpha chain on Dowex 50 and analysis of the 3H pyridoxal peptide showed that the
binding site of pyridoxal was the NH2-terminal valine. Pyridoxal was also found to bind to the
alpha chain of nonoxygenated hemoglobin. The rate of pyridoxyl-hemoglobin formation in a
cell-free system provided additional evidence in support of the suggestion that concentrative
uptake of pyridoxal by human erythrocytes is due to intracellular binding of pyridoxal to
hemoglobin. Pyridoxal phosphate and glucose, which also bind to the NH2-terminal valine, did not
reduce the accumulation of pyridoxal in the erythrocyte.
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Kark JA, Kale MP, Tarassoff
PG, Woods M, Lessin LS. (1978). Inhibition of erythrocyte sickling in vitro by
pyridoxal. J Clin Invest.
62(4):888-91.
To test the antisickling
activity of pyridoxal (Vitamin B-6), we compared the oxygen affinity and the percent sickling at
low PO2 of untreated erythrocytes with values for cells from the same blood sample incubated
with pyridoxal, glyceraldehyde, or pyridoxine. Pyridoxal increased oxygen affinity much more
than glyceraldehyde. 20 mM pyridoxal and glyceraldehyde had equivalent antisickling activity. At
PO2 levels above 20 mm Hg, both agents reduced sickling to less than 2%. In samples examined by
electron microscopy, pyridoxal reduced the percent sickled cells and the percent cells that
contain hemoglobin S fibers by the same amount (from 74 to 3%). Pyridoxine had no effect on
oxygen affinity or sockling. Pyridoxal reacts with intracellular hemoglobin to increase oxygen
affinity, which inhibits hemoglobin S polymerization and sickling.
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