Limits...
Omega-3 PUFAs Lower the Propensity for Arachidonic Acid Cascade Overreactions.

Lands B - Biomed Res Int (2015)

Bottom Line: A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic window which is widened by n-3 nutrients.The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions.Tools have been developed to aid deliberate day-to-day quantitative management of the propensity for cascade overactivity in ways that can decrease the need for drug treatments.

View Article: PubMed Central - PubMed

Affiliation: 6100 Westchester Park Drive, Apartment 1219, College Park, MD 20740, USA.

ABSTRACT
A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic window which is widened by n-3 nutrients. The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions. Recognizing the factors that predispose the cascade to an unwanted overactivity gives a rational approach for arranging beneficial interactions between the n-3 and n-6 essential nutrients that are initial components of the cascade. Much detailed evidence for harmful cascade actions was collected by pharmaceutical companies as they developed drugs to decrease those actions. A remaining challenge is to understand the factors that predispose the cascade toward unwanted outcomes and create the need for therapeutic interventions. Such understanding involves recognizing the similar dynamics for dietary n-3 and n-6 nutrients in forming the immediate precursors of the cascade plus the more vigorous actions of the n-6 precursor, arachidonic acid, in forming potent mediators that amplify unwanted cascade outcomes. Tools have been developed to aid deliberate day-to-day quantitative management of the propensity for cascade overactivity in ways that can decrease the need for drug treatments.

No MeSH data available.


Balancing prostaglandin formation and action. The prostaglandin part of the arachidonic acid cascade begins with a stimulated phospholipase A2 releasing precursor HUFA from membrane phospholipids. The relative intensity of reaction for n-3 and n-6 mediators is shown as a ratio next to the interacting enzyme or receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4537720&req=5

fig1: Balancing prostaglandin formation and action. The prostaglandin part of the arachidonic acid cascade begins with a stimulated phospholipase A2 releasing precursor HUFA from membrane phospholipids. The relative intensity of reaction for n-3 and n-6 mediators is shown as a ratio next to the interacting enzyme or receptor.

Mentions: The relative intensity of action by the n-3 eicosapentaenoic acid (20:5n-3) relative to that for the n-6 eicosatetraenoic acid (20:4n-6) in the prostaglandin part of the cascade is shown in Figure 1 as a ratio next to the enzymatic step or specific receptor. The initial step of phospholipase release of the precursor does not discriminate between the n-3 and n-6 structures, giving ratios of 1.0 for both cytosolic (cPLA2) and secretory (sPLA2) hydrolase actions. In contrast, both cyclooxygenases, COX-1 and COX-2, react more slowly with the n-3 than the n-6 substrate, giving cascade-mediated actions that are less intense with the n-3 precursor [15]. Different proportions of n-3 and n-6 precursors in cellular membrane lipids give different intensities of n-6 agonist action, and weak n-3 agonist action inevitably becomes an antagonist of the more potent n-6 agonist.


Omega-3 PUFAs Lower the Propensity for Arachidonic Acid Cascade Overreactions.

Lands B - Biomed Res Int (2015)

Balancing prostaglandin formation and action. The prostaglandin part of the arachidonic acid cascade begins with a stimulated phospholipase A2 releasing precursor HUFA from membrane phospholipids. The relative intensity of reaction for n-3 and n-6 mediators is shown as a ratio next to the interacting enzyme or receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4537720&req=5

fig1: Balancing prostaglandin formation and action. The prostaglandin part of the arachidonic acid cascade begins with a stimulated phospholipase A2 releasing precursor HUFA from membrane phospholipids. The relative intensity of reaction for n-3 and n-6 mediators is shown as a ratio next to the interacting enzyme or receptor.
Mentions: The relative intensity of action by the n-3 eicosapentaenoic acid (20:5n-3) relative to that for the n-6 eicosatetraenoic acid (20:4n-6) in the prostaglandin part of the cascade is shown in Figure 1 as a ratio next to the enzymatic step or specific receptor. The initial step of phospholipase release of the precursor does not discriminate between the n-3 and n-6 structures, giving ratios of 1.0 for both cytosolic (cPLA2) and secretory (sPLA2) hydrolase actions. In contrast, both cyclooxygenases, COX-1 and COX-2, react more slowly with the n-3 than the n-6 substrate, giving cascade-mediated actions that are less intense with the n-3 precursor [15]. Different proportions of n-3 and n-6 precursors in cellular membrane lipids give different intensities of n-6 agonist action, and weak n-3 agonist action inevitably becomes an antagonist of the more potent n-6 agonist.

Bottom Line: A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic window which is widened by n-3 nutrients.The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions.Tools have been developed to aid deliberate day-to-day quantitative management of the propensity for cascade overactivity in ways that can decrease the need for drug treatments.

View Article: PubMed Central - PubMed

Affiliation: 6100 Westchester Park Drive, Apartment 1219, College Park, MD 20740, USA.

ABSTRACT
A productive view of the benefits from omega-3 (n-3) nutrients is that the dietary essential omega-6 (n-6) linoleic acid has a very narrow therapeutic window which is widened by n-3 nutrients. The benefit from moderate physiological actions of the arachidonic acid cascade can easily shift to harm from excessive pathophysiological actions. Recognizing the factors that predispose the cascade to an unwanted overactivity gives a rational approach for arranging beneficial interactions between the n-3 and n-6 essential nutrients that are initial components of the cascade. Much detailed evidence for harmful cascade actions was collected by pharmaceutical companies as they developed drugs to decrease those actions. A remaining challenge is to understand the factors that predispose the cascade toward unwanted outcomes and create the need for therapeutic interventions. Such understanding involves recognizing the similar dynamics for dietary n-3 and n-6 nutrients in forming the immediate precursors of the cascade plus the more vigorous actions of the n-6 precursor, arachidonic acid, in forming potent mediators that amplify unwanted cascade outcomes. Tools have been developed to aid deliberate day-to-day quantitative management of the propensity for cascade overactivity in ways that can decrease the need for drug treatments.

No MeSH data available.