The adducts that form when
aldehydes modify
proteins have been implicated in the pathogenesis of
vascular disease and aging. Our previous studies indicated that
p-hydroxyphenylacetaldehyde (pHA), the major product of
L-tyrosine oxidation by the
myeloperoxidase/
hydrogen peroxide/
chloride system of phagocytes, covalently modifies the epsilon-amino group of
lysine residues at sites of
inflammation. Here, we report that pHA also reacts with the amino group of synthetic
phospholipids and red blood cell model systems. Using fast atom bombardment mass spectrometric analysis of
ethanolamine glycerophospholipid or
serine glycerophospholipid incubated with pHA and NaBH3CN, we detected products that were consistent with reduced
phospholipid Schiff base adducts. We confirmed the reaction of the
aldehyde with the amino group through 1H NMR and mass spectrometric analysis of polar headgroups recovered from the modified and reduced parent
lipid. When
phospholipid model systems and cell membranes were exposed to physiological levels of
L-tyrosine and the
myeloperoxidase/
hydrogen peroxide/
chloride system followed by treatment with NaBH3CN, reduced
Schiff base adducts of pHA with
ethanolamine glycerophospholipid and
serine glycerophospholipid (pHA-PE and pHA-PS, respectively) were produced. The reaction required
myeloperoxidase,
hydrogen peroxide,
L-tyrosine, and
chloride ion; it was inhibited by
catalase or
heme poisons, implicating
hydrogen peroxide and
peroxidase in the pathway. Collectively, these results demonstrate that an
aldehyde generated by the
myeloperoxidase system of phagocytes can covalently modify the amino groups of
phosphatidylethanolamine and
phosphatidylserine. Because amino
glycerophospholipids are critical components of cell membranes and
circulating lipoproteins such as
LDL, similar reactions may play important roles in the initiation or progression of disease at sites of
inflammation.