Abstract
We have studied LTA 4 and LTB 4 synthesis in a cell-free system from RBL-1 cells. All the enzymes leading to the formation of LTB 4 from arachidonic acid are localized in the soluble fraction (100, 000 x g supernatant) of these cells. The formation of LTA 4 and LTB 4 is complete by 10 min. When we varied the arachidonic acid concentration from 1 to 300 μM, the synthesis of LTB 4 leveled off at 30 μM and of LTA 4 at 100 μM while 5-HETE had not reached a plateau at 300 μM. This enzyme system has the capacity to generate relatively large amounts of 5-HETE and LTA 4 and only a relatively small amount of LTB 4. Therefore, the rate limiting step is not the 5-lipoxygenase, the first step in the pathway, but the conversion of LTA 4 to LTB 4. This is in contrast to cyclooxygenase pathway where the first step is rate limiting. A second addition of arachidonic acid at submaximal concentration for LTA 4 synthesis did not produce any additional LTA 4 or LTB 4. Further study of this phenomenon showed that the 5-lipoxygenase and LTA-synthase were inactivated with time by preincubation with arachidonic acid and that peroxy fatty acids seem to be the inactivating species.
Published Version
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