Mead acid

In general for the C20 series, maximal activity is achieved with amides of arachidonic acid (1) [81], mead acid (199) [149], and dihomo-y-linoleic acid (200) [150] (see Table 6.18). Decreasing the unsaturation (201), (202), or abolishment of the n-pentyl chain (203) [150] led to less active or inactive compounds. Variable results were seen with longer chains. The C22 4 n-6 analogue (204) is as active as AEA (1) whereas the C22 6 n-3 analogue (205) is less active than the C20 5 n-3 analogue (203) [150]. Replacement of the double bonds with triple bonds (206) resulted in loss of activity [150] (see Table 6.18). Forcing the fatty acid chain into a hairpin conformation by cyclisation (207) also resulted in inactive compounds [151]. 

Essential fatty acid deficiency Deficiency of linoleic acid, linolenic acid, and/or arachidonic acid, characterized by hair loss, thinning of skin, and skin desquamation. Long-chain fatty acids include trienes (containing three double-bonds [e.g., 5,8,11-eicosatrienoic acid, or Mead acid trienoic acids) and tetraenes (containing four doublebonds [e.g., arachidonic acid]). Biochemical evidence of essential fatty acid deficiency includes a trieneitetraene ratio greater than 0.4 and low linoleic or arachidonic acid plasma concentrations. 

The enzymes catalyse desaturation in sequence for example, the A desaturase converts stearate to oleic acid, which is converted, by the A desaturase, to the di-unsaturated fatty acid (18 2n-9), which is elongated to form eicosadienoic acid, which can be converted by the A -desaturase to the tri-unsaturated fatty acid (20 3n-9) which is known as Mead acid (see below). 

A functional method for detection depends upon competition for the activity of the and desaturases between a non-essential fatty acid (e.g. oleic acid) and an essential fatty acid (see above). If the latter is deficient, oleic acid is readily converted, via the desaturases, to Mead acid, since there is little competition (Figure 11.14). Hence the amount of the latter can be used as a marker for deficiency of essential fatty acids, although it is better to use the ratio of double bonds only three are present in Mead acid (i.e. a triene) but four are present in arachidonic acid (i.e. a tetraene). A ratio in plasma, triene/tetraene >4.0 is an indication of a deficiency of essential fatty acids. This method has shown that a deficiency can occur in a number of conditions which can lead to disease (Table 11.5). 

Mead acid not known Precursor of LT3 Mutant 427 33 141 1.9 Conversion of OA... 

Eicosatrienoic acid (ETA 20 3, n-9 Mead acid) (here a double mutant of the parent fungus was produced that lacked both delta-12 and delta-15 desaturase activities so that oleic acid, 18 1,n-9, could only be desaturated between its existing double bond and the carboxylate head group). 

Oleic acid (18 1 tjj9), a monounsaturated fatty acid, is the major fatty add in human milk. Oleic acid, as well as the products resulting from its further desaturation and elongation, are called the omegit-9 fatty adds. The omega-9 fatty acid 24 l(u9 is a major fatty acid in the membranes of nerves. The omega-9 fatty add 20 3to9 is called the Mead acid. Mead acid accumulates in the body in response to a defi-... 

How many separate steps of desaturation and elongation are required to convert oleic acid to the Mead acid ... 

The question of which dietary practices Jead to EFA deficiency is difficult to predict. A study of women suffering from anorexia nerv osa, a disease that provokes pathological fasting behavior and marked weight loss, indicated that the women w ere not deficient in EFAs. Surprisingly their plasma levels of Mead acid were lower, rather than higher, than those of control human subjects (Holman et a ., lyysj-... 

FIGURE 9.102 Accumulation of Mead acid (20 3essential fatty acids. (Redrawn with permission from Richardson and Sgoutas, 1975.)... 

The acetylenic analog of Mead Acid, 5,8,11-eicosatriynoic acid, was reported to be a selective inhibitor of platelet 12-lipoxygenase. Acetylenic fatty acids also inhibited 15-lipoxygenases of plant (soybean) as well as of animal (rabbit reticulocyte) origin. The nature of the acetylenic compound significantly affected its activity on the soybean enzyme, but not the rabbit enzyme. For the former, 7,10,13-eicosatriynoic acid was the most powerful inactivator. Addition of a fourth triple bond at position 4 or 5 strongly reduced the rate of inactivation. On the other hand, the rabbit reticulocyte enzyme was inactivated almost equally well by the various acetylenic fatty acids that were tried. The mechanism of inactivation of lipoxygenases was also suicide inhibition . ... 

Sometimes called Mead acid not usually important in fish or shellfish. 

The measurements of the total amount of various essential fatty acids as co-3 fatty acids in plasma, serum, or erythrocyte membrane phospholipids have been indicated as useful markers of essential polyunsaturated fatty adds. Essential fatty acid deficiency is a clinical condition that derives from inadequate status of co-3 and co-6 fatty acids however, the symptoms are nonspecific and may not present prior to marginal essential fatty acid status. Widely used biomarkers for bicx hemi( essai-tial fatty acid deficiency are mead acid and the triene/tetraene ratio. Howcvct, the total plasma triene/tetraene ratio has been considered the gold standard for essential fatty acid deficiency. Mead acid, or 5,8,11-eicosatrienoic acid (5,8,11-20 3 co-9) is synthesized from endogenous oleic acid and is increased when there is insufficient concentrations of linoleic and a-linolenic acid to meet the needs of polyunsaturated fatty acids. Under normal conditions only trace amounts of mead acid are found in plasma. EPA and DHA inhibit mead acid synthesis. Mead acid measurement is an indicator of essential fatty acid deficiency state, while essential fatty add depletion is associated with a decrease in plasma hnoleate and arachidonate percentages. Assessment of long-term essential fatty acid intake is measured in adipose tissue, and it is considered the best indicator because of its slow tumover. - Cutoff values for the assessment of essential fatty adds and to-3 fatty acid status in erythrocytes have been reported. Proposed cutoff values for children older than 0.2 years are 0.46 mol% 20 3 co-9 (mead acid) for early suspicion of essential fatty acid defidency, 0.068 mol/mol docosapentaenoic/arachidonic acid... 

C20 3co9 C20 3A5 Mead acid (discovered by James Mead) Anti-inflammatory effects... 

Oleic acid Eicosenoic acid Mead acid Eracic acid Nervonic acid... 

From experiments mainly with laboratory animals, it has been demonstrated that relatively high intakes of trans fatty acids in the diet in conjunction with marginal intakes of essential fatty acids (less than 2% dietary energy from linoleic acid) can lead to the presence of Mead acid (cis-5,8,11-20 3) in tissue lipids and an increase in the ratio of 20 3 n-9 to 20 4 n-6. This has been interpreted to suggest early signs of essential fatty acid deficiency, with potentially increased requirements for essential fatty acids. Mead acid can accumulate in the presence of linoleic acid, if large amounts of nonessential fatty acids are also present. Two mechanisms have been suggested to explain these observations in relation to intake of trans fatty acids ... 

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