The response of Borrelia burgdorferi to the challenge of reactive oxygen species (ROS) is a direct result of its limited biosynthetic capabilities and
lack of biologically significant levels of intracellular Fe.
In other bacteria, the major target for oxidative damage is DNA as a consequence of the reaction of ``free'' intracellular with ROS through the Fenton reaction. Therefore, cellular defenses in these bacteria are focused on protecting this essential cellular component.
This does not seem to be the case for B. burgdorferi. In this chapter, we describe methods that were used to analyze the potential targets for ROS in B. burgdorferi.
***Surprisingly, membrane lipids (e.g., linoleic and linolenic acids) derived from host are the major target of ROS in the Lyme disease spirochete.***
Posted by sparkle7 (Member # 10397) on :
Do you have the full article?
It's alittle hard to understand for the lay person.
Can you translate?
I'm also interested in your studies on gallium!
Posted by Marnie (Member # 773) on :
It appears our system is trying to destroy the proteins in Bb's outer cell walls by using ROS...free radicals...reactive oxygen species...
Those proteins are made of
linoleic and linolenic acids.
Whoa...that means the Omega 3 OILS maybe potentially harmful.
For the linolinic acid in them which is used to MAKE EPA and DHA.
Long chain omega 3s EFA and DHA come from the shorter chain omega 3 ALA.
EFA and DHA are okay, but it appears Bb's proteins contain the shorter chain omega 3 ALA.
DHA maybe especially beneficial.
Posted by Dawn in VA (Member # 9693) on :
We know the body makes Omega 3's from ALA
(although it's often a limited conversion, which is why we take EPA/DHA directly)
Marnie, is the reverse also true; can the body convert DHA/EPA back down to ALA or is it a one-way street?
Posted by Marnie (Member # 773) on :
Alpha-linolenic acid - an omega-3 fatty acid found in many vegetable oils
Second, clinical studies that are available suggest that alpha-linolenic acid may actually be dangerous for prostate cancer patients.
An epidemiology study that examines the association of alphalinolenic acid and prostate cancer risk has just been published.
Dr. Eduardo De Stefani and colleagues from Registro Nacional de Cancer, Montevideo, Uruguay, examined the association between prostate cancer and alphalinolenic acid, linoleic acid, total fat, saturated fat, and monounsaturated fat.
Addit-ionally, they tested whether there was a difference between alpha-linolenic acid obtained from animal or vegetable sources. One of the reasons this study is interesting is that Uruguay has one of the higher death rates from prostate cancer, as well as one of the highest rates of red meat consumption.
This study found that the major risk factors associated with the development of prostate cancer were family history of this disease and intake of alpha-linolenic acid.
When the risk was adjusted for intake of linoleic acid, saturated fat, monounsaturated fat, and red meat intake, those with the highest intake of alpha-linolenic acid had a 440% increase in risk compared with those at the lowest level.
Also, alpha-linolenic acid from both vegetable and animal sources was associated with an increase in the risk of prostate cancer.
There are now six epidemiology studies that have examined the association between dietary alpha-linolenic acid and risk of prostate cancer.
Five out of six of these studies found an increase in the risk of prostate cancer associated with alpha-linolenic acid. The one negative study is from Swe-den.
It is important to note that the Swedish study found this fatty acid had no impact and therefore did not show any benefit from alpha-linolenic acid.
Thus, six out of six studies found no benefit to in-creased alpha-linolenic acid, while five found potential harm!
I should also note that our laboratory, as well as others, found that alpha-linolenic acid is one of the most powerful growth stimuli for human prostate cancer cells.
I have been asked to comment on flaxseed compared with flaxseed oil.
My major concern is with flaxseed oil,
which permits patients to ingest very large a-mounts of alpha-linolenic acid in a short period of time.
While flaxseed contains alpha-linolenic acid, it is quite unlikely that someone will eat enough flaxseed to match the alpha-linolenic acid content of even a modest dose of the oil.
Addition-ally, flaxseed contains a number of phytochemicals, such as lignans, that are of potential value.
One of the major lignans in flaxseed is secoisolariciresinol, a phytoestrogen and antioxidant.
While I am not as concern-ed about the safety of flaxseed, I certainly do not recommend it as treatment for prostate cancer. In preparation for this issue of the newsletter, I have reviewed every paper on the health benefits of flax-seed in the National Library of Medicine database, Medline.
There is no evidence that flaxseed slows or prevents the growth and spread of prostate cancer. Rats fed flax-seed for their entire life have smaller prostate glands, but the dose required to do this altered the sexual performance and anatomy of both sexes.
Flaxseed and its lignans do appear to alter the development and spread of breast cancer and melanoma in animal models and may have benefit for patients with these diseases.
There is considerable evidence that flaxseed intake can reduce your risk of heart disease and ameliorate the damage caused by rheumatoid arthritis.
Some patients have written to say that they have heart disease, and my stance means they must chose whether to treat their heart and stay on flaxseed oil or discontinue it to treat their prostate.
There are other effective options available for preventing or treating heart disease.
For example, cholesterol-lowering drugs, such as Pravachol, Lipitor, and Zocor are effective at lowering cholesterol and have a favorable influence on the outcome of heart disease.
I might also mention that there are other sources of antioxidants and phytoestrogens with greater evidence to support their use by prostate cancer patients:
The metabolism of -linolenic acid in humans has been well characterized.
***After -linolenic acid is ingested, the body converts it to very-long-chain polyunsaturated fatty acids: readily to eicosapentaenoic acid (20:5n-3) and more slowly to docosahexaenoic acid (22:6n-3).***
***A major consequence of -linolenic acid deficiency is that its chief synthetic end product, docosahexaenoic acid, is not adequately produced (2).***
Because docosahexaenoic acid is a major component of the phospholipid membranes of the brain and retina, its deficiency in these organs then leads to abnormal function (3).
n-3 Fatty acid deficiency is accentuated when there is simultaneously a high content of linoleic acid in the diet, which tends to inhibit the synthesis of docosahexaenoic acid from linolenic acid.
Thus, diets rich in corn, safflower, sunflower, and peanut oils, all of which are high in linoleic acid and low in -linolenic acid, can lead to n-3 fatty acid deficiency
Thus, a high ratio of n-6 to n-3 fatty acids in the diet accentuates n-3 fatty acid deficiency.
***Long chain omega 3s EFA and DHA come from the shorter chain omega 3 ALA.***
Both 5,8,11,14,17-eicosapentaenoic acid and 4,7,10,13,-16,19-docosahexaenoic acid, major constituents of fish oils, inhibited adenosine diphosphate-induced aggregation of platelets and the accompanying release of mitogens.
These effects are dose dependent. Linolenic acid the biosynthetic precursor of eicosapentaenoic acid, also inhibited platelet aggregation and mitogen release.
Eicosapentaenoic acid also inhibited mitogen release from human monocyte-derived macrophages, which, in vivo, are an additional source of mitogens during atherogenesis.
Potent inhibition of human platelet aggregation and mitogen release was also seen with dihomo-γ-linolenic acid (8,11,14-eicosatrienoic acid ), whose levels are reportedly elevated in Eskimos subsisting on marine diets.
We conclude that diets that elevate plasma and/or tissue levels of eicosapentaenoic acid, docosahexaenoic acid and dihomo-γ-linolenic acid precursor γ-linolenic acid ) may exert antiatherosclerotic effects by inhibiting the release of mitogens from platelets and other cells.
Note: phosphatidylserine is used to rebalance the HPA axis.
This study shows that a metabolite of an essential dietary fatty acid, linoleic acid, can modulate tyrosine phosphorylation and activity of key signal transduction proteins in a growth factor mitogenic pathway.
But if linoleic acid is oxidized, it can't do the above (modulate tyrosine phosphate transfer)
OXIDIZED PRODUCTS OF LINOLEIC ACID STIMULATE ADRENAL STEROIDOGENESIS
Steroidogenesis is the process wherein desired forms of steroids are generated by transformation of other steroids. Products of steroidogenesis include: · androgens o testosterone · estrogens and progesterone · corticoids o cortisol o aldosterone
These results suggest that Cu(II) complexes can not only oxidize linoleic acid, but also decompose LOOH generated from it.
ROS can harm/destroy cysteinyl residues, iron-sulphur clusters, DNA and polyunsaturated lipids, leading to inhibition of growth or cell death.
Unlike most bacteria, B. burgdorferi incorporates ROS-susceptible polyunsaturated fatty acids from the environment into their membranes.
It intentionally adds the fatty acid that *is the most easily oxidized* into its protein cell wall(likely to protect its "innards".
ALPHA.-Linolenic Acid-rich *Diacylglycerol*
The enzyme was named phospholipid: diacylglycerol acyltransferase (PDAT).