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 leukotriene formation and action. The leukotriene 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 enzyme or receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4537720&req=5

fig2: Balancing leukotriene formation and action. The leukotriene 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 enzyme or receptor.

Mentions: For the leukotriene portion of the cascade shown in Figure 2, the first two steps, PLA2 and 5-lipoxygenase (5-LO), are relatively indiscriminate, whereas the leukotriene C synthase (LTCS) forms cysteinyl leukotrienes 10-fold [17] to 20-fold [18] less vigorously with n-3 than n-6 LTA intermediates. The lower intensity of LTC formation allows a higher proportion of n-3 in HUFA to lower the intensity of chronic bronchopulmonary events seen in asthma and chronic obstructive pulmonary disease (COPD). Additionally, the LTB receptor (BLT-1) that mediates important immune-inflammatory events responds 50-fold less vigorously to n-3 LTB5 than the potent n-6 LTB4 [19], making the development of severe inflammatory loci less intense when the HUFA balance has more n-3 HUFA.


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

Lands B - Biomed Res Int (2015)

Balancing leukotriene formation and action. The leukotriene 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 enzyme or receptor.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Balancing leukotriene formation and action. The leukotriene 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 enzyme or receptor.
Mentions: For the leukotriene portion of the cascade shown in Figure 2, the first two steps, PLA2 and 5-lipoxygenase (5-LO), are relatively indiscriminate, whereas the leukotriene C synthase (LTCS) forms cysteinyl leukotrienes 10-fold [17] to 20-fold [18] less vigorously with n-3 than n-6 LTA intermediates. The lower intensity of LTC formation allows a higher proportion of n-3 in HUFA to lower the intensity of chronic bronchopulmonary events seen in asthma and chronic obstructive pulmonary disease (COPD). Additionally, the LTB receptor (BLT-1) that mediates important immune-inflammatory events responds 50-fold less vigorously to n-3 LTB5 than the potent n-6 LTB4 [19], making the development of severe inflammatory loci less intense when the HUFA balance has more n-3 HUFA.

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.