Travis
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- Jul 14, 2016
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That's a nice shift, and thanks for reminding me of the rare arachidic (20∶0) and behenic acids (22∶0). There are approximately zero studies on giving animals these two fatty acids, and they might perhaps make the membrane 'too stiff.' After reading about the B-series leukotrienes I have decided to go full deficient; the few times I eat eggs the yolks go straight down the sink—no grains, no seeds, no beans (redundant, I know), no avocado, and no nuts besides the coconut.
The B-series leukotrienes were first discovered for their powerful effect on immune cells. This is their canonical function, and in the process of acting upon upon their leukotriene membrane receptors they have been shown to: increase antibody complement affinity sites, initiate the degranulation process, and even serve as very powerful chemoatractants for all polymorphonuclear leukocytes (i.e. neutrophils, eosinophils, and basophils).
The fact that the E-series prostaglandins vary in potency depending on the number of double bonds they have—which, in turn, depends on the diet—is relatively well-known compared to the fact that also do the B-series leukotrienes. There exists only two real E-series prostaglandins on account of Mead acid's (20∶3) cyclooxygenase product not even resembling the other two, completely lacking the cyclopentenone ring structure that puts 'cyclo' in cyclooxygenase—thus being unfit to classified as such. Eicosapentaenoic acid (20∶5) forms the only other cyclopentenone cyclooxygenase products, and these all have one more double bond than the arachidonic acid products (20∶4). The process of endoperoxide cycloaddition of peroxynitrite onto arachidonic acid always desaturates two bonds, giving arachidonic acid products having only two double bonds and a subscript to match. In the very same way, the eicosapentaenoic acid products are denoted by the number three—having this number of double bonds. Prostaglandin E₁ is not the Mead acid product (20∶3ω−9), as you'd might expect, but the dihomo-γ-linolenic acid product (20∶3ω−6). Both the 1-series and 2-series prostaglandins derive from ω−6 fatty acids and both are similarly more potent than the 3-series derived from eicosapentaenoic acid (20∶5ω−3). Most studies geared towards quantifying the differential potency between the three species indicate that the 3-series prostaglandins are approximately four times less potent than the 1-series and 2-series prostaglandins.
But perhaps even more relevant, and what some may even find astonishing, is that the potency of the B-series leukotrienes vary between 10 and 10³-fold. The least potent is the eicosapentaenoic acid (20∶5ω−3) product, having an effect on neutrophils only ¹⁄₁₀₀₀ as great as the arachidonic acid product leukotriene B₄. The leukotriene derived from the ω−3 fatty acids is commonly known as leukotriene B₅, and because the enzyme lipoxygenase does not cyclicize the lipid—or change the double bonds in any way besides stereochemically—the leukotrienes have the same unsaturation index as their parent lipids.
Intermediate in potency is the Mead acid (20∶3ω−9) product, having roughly ten times less the chemoattractant potency on neutrophils. You might assume that this would be called leukotriene B₃ . . . and you'd be right, of course, but this is not what is actually formed.
The lipoxygenase product of Mead acid had been presumed before it's been found in vivo due to the mythological nature of the beast. Since the de novo formation of Mead acid—an elongation product of oleic acid—requires the near-complete avoidance of all ω−6 fatty acids, Mead acid is generally not found in modern humans; nor is this found in lab animals fed the standard diet, and hence neither is its cycloxygenase product or the leukotriene derived from it. For this reason, the chemical structure of leukotriene B₃ was extrapolated from those of leukotrienes B₃ and B₅. This leukotriene has been synthesized, is an available research chemical, and has been used in white blood cell migration assays—among other assay types—where it gives comparable potency as our maligned leukotriene B₄ ultimately derived from linoleic acid.
In the early 1980s, the presumed Mead acid derivative leukotriene B₃ was found to be a unicorn. The structure extrapolated from the other, more common B-series leukotrienes contains one trans double bond; although this molecule is actually made my Mead acid through lipoxygenase, this is a relatively minor isomer. The actual main products of Mead acid + lipoxygenase are two enantiomers both having three cis double bonds having the IUPAC designations of 5S,12R-dihydroxy-6Z,8Z,10Z-eicosatrienoic acid and 5S,12S-dihydroxy-6Z,8Z,10Z-eicosatrienoic acid. I use the term all-cis-leukotriene B₃ to differentiate it from is unphysiological presumption, which goes by the names of: trans-leukotriene B₃, unicorn-leukotriene B₃, or simply leukotriene B₃ (it's too established). All-cis-leukotriene B₃ has approximately ten times less chemoattractant ability as leukotriene B₄, meaning that you'd expect all leukocytes to be inclined to home-in on the arachidonic acid product anywhere from 10 to 10³ times more than our natural eicosapentaenoic and Mead acid products—these being leukotriene B₅ all-cis-leukotriene B₃.
In the absence of dietary ω−6 fatty acids, their formation in the body can still occur. Although humans don't have a Δ⁶-desaturase enzyme, helminths and fungi do. The pathological yeast/fungi Candida albicans is known to synthesize arachidonic acid de novo, which it will even form prostaglandin E₂ with despite not having a genetic sequence homologous to mammalian cyclooxygenase. The B-series leukotrienes would be expected to form in the process, and even nonenzymatically as they are simply hydroxylated lipids (and especially in the presence of a neutrophil attack, which releases superoxide towards the pathogen). Since primate leukocytes have evolved in the tropics where both helminth infections are more common and plants do not synthesize ω−6 fatty acids, I maintain that the relatively potent chemoattraction of leukotriene B₄ on leukocytes had more-or-less evolved as a fungi- and helminth-seeking device. The fact that eosinophils will follow a leukotriene B₄ gradient while also containing a toxic cargo in its cytosol—containing eosinophil basic protein, eosinophil neurotoxin, and eosinophil peroxidase—which has been shown to kill helminths upon degranulation further this idea. Accepting this line of line of thinking eventually leads to the thought that the unnatural ω−6-derived leukotriene B₄ will decrease immunological sensitivity by increasing background levels over that found in the vicinity of helminths and yeast. Eosinophils have also been shown to be attracted to 13-hydroxylinoleic acid with roughly ²⁄₃·leukotriene B₄ potency, but even this reduced attraction is far greater than even the most powerful ω−3 and ω−9 derivatives.
Then comes the avoidance of almonds, grains, seeds, olive oil, avocados . . . and the egg yolks start going down the sink.
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