Omega-3 Fatty Acids
What competes for substrates in ALA conversion of EPA/DHA?
15-desaturase (plants only)
What percent of adults have blood mercury concentrations >5.8 ug/L?
4% (1/20)
Docosahexaenoic (DHA) contains double bonds on carbons
4, 7, 10, 13, 16, and 19
Eicosapentaenioc (EPA) contains double bonds on carbons
5, 8, 11, 14, 17
What is the EPA's cut off for the dose of methylmercury without an appreciable lifetime risk of harm?
5.8 ug/L
Dietary induced changes in the FA composition of the plasma membrane is largely complete within...
6-8 weeks
What is the rate limiting step in ALA=>EPA/DHA conversion?
6-desaturase
@-linolenic acid (ALA) contains double bonds on carbons
9, 12, 15
ALA to DHA in men is limited to
<0.05%
ALA TO DHA in women of a reproductive age is limited to
<0.1%
ALA aka
@-Linolenic acid
Methylmercury
A neurotoxin that can impair normal neurological development in a fetus or child
Where does the b-oxidation step of the ALA=>EPA/DHA conversion take place?
A peroxisome (NOT mitochondria)
What is flaxseed a good source of?
EPA and ALA
What compounds can counter mercury?
EPA and DHA
Does farm-raised or wild-caught salmon contain more omega-3s?
Farm-raised
What is 5-desaturase aka
Fatty acid desaturase 1 (FADS1)
What is 6-desaturase aka
Fatty acid desaturase 2 (FADS2)
What is a good source of ALA?
Flax
Atlantic vs Mexican fish for Hg Concentration
Mexican> Atlantic -better to consume fish from the Atlantic ocean
What could account for the inconsistencies of effectiveness associated with fish oil supplements?
Oxidation of oils (between 11-62% of OTC supplements)
Various markers of oxidative stress and redox balance are affected by
Oxidized lipids
Salmon farmed in Europe has higher levels of ___ than that in South, Central, and North America
PCB
What organisms synthesize ALA?
Plants
What results in a much higher EPA concentration compared to ALA?
Stearidonic acid
Is mercury by itself bad?
Yeah, but methyl mercury is the dangerous one
Should you know the conversion pathways of ALA into EPA and DHA?
Yes
What are the only demographics the EPA recommends stays away from farm-raised salmon?
Young children and pregnant/nursing women
Which omega-3 FAs do fish oils contain?
EPA and DHA
ALA to EPA biosynthesis is limited at
0.2%
Where are DHA concentrations highest? How does this compare to EPA?
-DHA is highest in the *retina* and cerebral cortex -EPA is very low there
Is EPA or DHA a better supplement?
-EPA=> EPA -DHA=> EPA and DHA (retroconversion)
What are the potential routes of lipid oxidation?
-auto-oxidation -photo-oxidation -metal-catalyzed oxidation
DHA aka
Docosahexaenoic acid
Elongase enzyme FAQs
-Elovl2 and Elovl5 -multi-enzyme complexes similar to FA synthase -uses a 4-step chain rxn --> begins with a condensation reaction using malonyl-CoA
Digestion and absorption of FAs
-Fat droplet + Bile salt phospholipids => emulsion droplets *Lumen* *of* *Small* *Intestine* -emulsion droplets + Bile salts and pancreatic lipase => micelles -micelles--> free molecules of FAs and monoglycerides *Epithelial* *Cell* -diffusion of FAs and monoglycerides -triglyceride synthetic enzymes in the ER=> amphipathic proteins -amphipathic proteins--> droplets of triglyceride enclosed by membrane from ER *Lacteal* -droplets of triglycerides enter into Chylomicrons
What does RBC membrane EPA and DHA composition positively correlate with?
-blood plasma -platelet -WBC -adipose -breast milk -skeletal and cardiac mm -brain gray matter
What can omega 3s treat?
-hypertriglyceridemia -heart disease -insulin resistance -cancer -neurodegenerative diseases -depression/anxiety -inflammatory diseases -asthma
Oxidized lipids (as a result of lipid membrane peroxidation) can cause
-inflammation -atherosclerosis -DNA damage leading to carcinogenesis
Functions of omega 3s (EPA/DHA)
-major substrates for the phospholipid membrane -cellular energy production -adipose storage -modulation of pleiotropic functional properties at the cellular level
SMASHT
-salmon -mackerel -anchovies -sardines -herring -tuna
How can the "fish burp" side effect be avoided in oral omega-3 supplements?
-taking the supplement with meals -ingesting enteric-coated capsules
If fish contains 10-1000 ppb of mercury, why do fish oil supplements contain way less amounts of mercury?
1) use of smaller fish, lower on the food chain (less Hb accumulation) 2) mercury binds to *amino* *acids* (meat) not oil 3) mercury can be reduced or removed during processing (distillation)
What acts as a precursor to EPA and DHA?
ALA
What is the most rapidly oxidized unsaturated FA?
ALA
What is the current reasoning for the poor conversion of ALA to DHA?
ALA is the most rapidly oxidized unsaturated FA, so a large portion of ingested ALA is b-oxidized to acetyl-CoA
Do fish synthesize or accumulate omega-3 FAs?
Accumulate, via microalgae or prey fish
When is the ability to convert EPA to DHA (to an appreciable extent) lost?
After infancy
What does alcohol inhibit and what can this result in?
Alcohol inhibits 5- and 6-desaturase and this can reduce EPA and DHA concentrations
What type of FA is ALA
An essential fatty acid
Why are polyunsaturated fatty acids so susceptible to oxidation?
Because the double bonds between the carbons in the polyunsaturated FA are sp2 hybridized -the p-p(pi) bond electrons are easy to grab and pull away by free radicals
At high enough levels, dioxins, PCBs, and chlordane are suspected to be
Carcinogens
The activity of which enzymes are increased with increased lipid peroxidation?
Catalase and glutathione peroxidase
What type of fish contains the most EPA/DHA?
Cold water oily fish (SMASHT)
What type of FA are EPA and DHA
Conditional fatty acids
What supplement could be used for male fertility?
DHA -high content can be found in sperm
What is the only way to attain high levels of EPA and DHA in the blood and cell membranes?
Dietary intake
Farm-raised salmon contains less mercury than wild caught salmon, but also has higher levels of
Dioxins, polychlorinated biphenyls (PCB), and chlordane
Why does the FDA recommend limiting ingestion of predatory fish?
Due to its high levels of toxic contaminants (such as mercury)
Which fats are more susceptible to lipid oxidation and why?
EPA and DHA because they have more double bonds (5/6)
EPA aka
Eicosapentaenoic acid
What are the most common free radicals that oxidize the p-p(pi) bond and form lipid carbon-centered radicals (L*)?
Hydroxyl radicals
In the case of lipid oxidation, patients have: -increased plasma and urinary: -decreased plasma levels of:
Increased: -malondialdehyde (MDA) -oxLDL -8-oxoGuanine Reduced: -vitamin C -vitamin E
What does 6-desaturase activity decrease with?
Increasing age
Why is vitamin E added to fish oil supplements?
It acts as a preservative and free radical quencher
What can happen if LA concentrations become to high?
Limited production of EPA and DHA (competition for 6-desaturase)
What are produced when free radicals oxidize the p-p(pi) bond?
Lipid carbon-centered radicals (L*)
Is flax a good source of DHA?
No
Are there any bleeding disorders associated with large doses of EPA?
No, Eskimos consume 6 g/day and are fine
How are hydroperoxides produced?
Occurs when fish oils oxidizes over time, breaking down the compounds into secondary oxidation products (aldehydes, ketones, and short chain FAs), causing the unpleasant odors associated with rancid oils
What acts as a valid test with a reliable index of habitual dietary intake of omega-3s?
RBC membrane EPA/DHA
What is the last step of ALA=>EPA/DHA conversion?
The b-oxidation step
Why do cold water fish contain so many omega-3 FAs?
The double bonds allow the cell membranes to be more fluid so that they don't freeze in the water
Where does all but the last step of ALA=>EPA/DHA conversion take place?
The smooth ER
What do the double bonds in fatty acids supply and allow for?
They supply rigidity and allow for 3-D rotation
Is krill or fish oil better for absorbing omega-3s?
They're the same
What competes with ALA for access to 6-desaturase?
linoleic acid (LA)
