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By Artemis P Simopoulos; Robert R Kifer; Roy E Martin; National Institutes of Health (U.S.). Nutrition Coordinating Committee.; National Fisheries Institute

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1. Enhancement of Eicosanoid Accumulation by lipid Hydroperoxides. The rapid amplification of hydroperoxides permits an explosive burst of synthesis that exceeds the rate of metabolic inactivation and permits eicosanoid interaction with receptors to give pathophysiological effects (ref. 6, Reprinted with permission of Dr. T. ). η-6 = ω-6. A c c u m u l a t i o n ( a n d p h y s i o l o g i c a l effect) s e l d o m o c c u r s u n d e r n o r m a l c o n d i t i o n s s i n c e t h e total c a p a c i t y o f a t i s s u e to f o r m e i c o s a n o i d s is s e l d o m fully e x p r e s s e d * , a n d in n o r m a l t i s s u e s it s e e m s to b e u n d e r t h e c o n t i n u a l c o n s t r a i n t s o f a l i m i t e d s u p p l y o f e i t h e r t h e s u b s t r a t e a r a c h i d o n i c acid or the hydroperoxide activators (7).

S t u d i e s in n o r m a l i n d i v i d u a l s w i t h t h e p r e s u m e d a c t i v e i n g r e d i e n t s o f a f i s h - o i l - e n r i c h e d d i e t a r e critical t o t h e u l t i m a t e a n a l y s i s o f t h e effects o f s u c h a diet in i n d i v i d u a l s w i t h p a t h o b i o l o g i c s t a t e s . Clinical i n v e s t i g a t i o n s a l r e a d y in p r o g r e s s a n d at t h e s t a g e o f d a t a a n a l y s i s w i t h a p p r o p r i a t e b i o c h e m i c a l a s s e s s m e n t o f v a r i o u s cell p o p u l a t i o n s i n v o l v e r h e u m a t o i d arthritis, b r o n c h i a l a s t h m a , a n d s y s t e m i c l u p u s e r y t h e m a t o s u s .

2. 3. 4. C o m p e t e for a c c e s s to t h e o x y g e n a s e ( s ) . D e c r e a s e t h e amplification o f h y d r o p e r o x i d e s . Inactivate the oxygenase(s). F o r m a l t e r n a t e e i c o s a n o i d s ( w e a k a g o n i s t / a n t a g o n i s t at r e c e p t o r s ) . 1 pmole/min/g body weight. 001% of the overall synthetic capacity may be used during a normal day. William E. M. Lands 36 II. ACCESS OF POLYUNSATURATED FATTY ACIDS TO CYCLOOXYGENASE S o o n after r e c o g n i z i n g t h a t t h e t w e n t y - c a r b o n p o l y e n o i c a c i d s c o u l d b e precursors of prostaglandins (8,9), investigators demonstrated that the oxidative cyclization occurred with the non-esterified form of the substrate acid r a t h e r t h a n w i t h t h e m o r e a b u n d a n t cellular s t o r e s esterified to p h o s p h o l i p i d s ( 1 0 ) .

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