Cej

HETEs 3-Series PGs HETEs Docosahexaenoic Acid

approximately 15:1. Evidence for this change in diet through history comes from studies on the evolutionary aspects of diet, modern-day hunter-gatherers, and traditional diets. Modern agriculture has led to a substantial increase in n-6 fatty acids at the expense of n-3 fatty acids, which has resulted in excessive consumption of n-6 fatty acids by humans.

The n-6 EFAs have two main functions. First, they act as structural components of membranes forming the basis of the phospholipid component of the lipid bilayer of plasma membranes in every cell in the body, thus providing a membrane impermeable to most water-soluble molecules. The length and degree of saturation of the fatty acids determine how the phospholipid molecules pack together and consequently affect membrane fluidity, signal trans-duction, and the expression of cellular receptors. The second role of n-6 fatty acids is as precursors to the eicosanoids (Figure 1). The eicosanoids are a family of 'hormone-like' compounds including prostaglandins (PGs), leukotrienes (LTs), and hydroxy- (HETEs), dihydroxy- (DiHETEs), and epoxy- (EETs) fatty acids. Eicosanoids, however, are distinct from most hormones in that they act locally, near their sites of synthesis, and they are catabolized extremely rapidly. Thus, they are considered to be locally acting hormones. The eicosanoids modulate renal and pulmonary function, vascular tone, and inflammatory responses. The enzymes involved in AA metabolism include the cyclooxygenases and lipoxygenases, which yield the 2-series PGs and 4-series LTs, respectively. Lipoxygenase also utilizes AA for the formation of the HETEs. A third pathway for the utilization of AA involves the cytochrome P-450 enzymes found in the liver, kidney, lung, intestines, heart, small blood vessels, and white blood cells. AA metabolized via cytochrome P-450 yields EETs, DiHETEs, as well as HETEs. The cytochrome P-450 metabolites play an important role as paracrine factors and second messengers in the regulation of pulmonary, cardiac, renal, and vascular function and modulate inflammatory and growth responses.

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