Ferrylmyoglobin, the high oxidation state of myoglobin analogous to co
mpound II of peroxidases, promotes the peroxidation of palmitoyl-linol
eyl-phosphatidylcholine (PLPC) large unilamellar vesicles. This was as
sociated with oxygen consumption and a slow conversion of ferrylmyoglo
bin to metmyoglobin. The time course of oxygen consumption was charact
erized by the occurrence of a lag phase, which could be overcome by th
e addition of sodium deoxycholate to the reaction mixture. The rate of
conversion of ferrylmyoglobin to metmyoglobin was slower than that of
oxygen consumption, and there was not stoichiometric correlation betw
een both events. These findings suggest that the observed oxygen consu
mption linked to lipid peroxidation is supported by a peroxidatic acti
vity encompassed by the frrnylmyoglobin double left right arrow metmyo
globin transition as well as free radical propagation reactions. Incub
ation of metmyoglobin with PLPC vesicles containing 3% hydroperoxide r
esulted in oxygen consumption, the time course of which was devoid of
the lag phase observed with hydroperoxide-free unilamellar lipid vesic
les. The incubation of metmyoglobin with peroxide-containing PLPC vesi
cles or with equimolar amounts of lipid hydroperoxide was not associat
ed with Soret or visible absorption spectral changes of metmyoglobin,
which could be ascribed to its conversion to ferrylmyoglobin. Treatmen
t of the metmyoglobin/lipid hydroperoxide mixtures with Na2S did not l
ead to the formation of the sulfheme protein derivative, which can be
considered as a fingerprint for the occurrence of ferrylmyoglobin. Des
pite the lack of evidence for formation of the latter species, metmyog
lobin catalyzed efficiently the conversion of palmitoyl-linoleyl-phosp
hatidylcholine hydroperoxide (PLPCOOH) to various products, which have
been tentatively identified as conjugated carbonyl compounds (with ab
sorption maxima at 233 and 270 nm), and a set of lower molecular weigh
t and/or higher polarity derivatives containing the conjugated diene m
oiety (with differing intensity of absorption maxima at 233 nm). The p
athophysiological implications for the phospholipid hydroperoxide/metm
yoglobin interaction appear to broaden the range of oxidizable targets
of this hemoprotein in a manner other than that involving the reactiv
e oxoferryl complex of its high oxidation state.