29) Essential Fatty Acids
2) Could capsules containing purified EPA ethyl ester be used instead of fish oil to effectively treat the DHA deficiency in this patient?
My Guess - yes b/c EPA can be converted to DHA in the body
What are the AIs for children (A) 1-3 and (B) 4-8 years for: 1) 18:2n-6 2) 18:3n-3
(A) Children 1-3 Years 1) 18:2n-6 = 7 grams 2) 18:3n-3 = 0.7 grams (B) Children 4-8 Years 1) 18:2n-6 = 10 grams 2) 18:3n-3 = 0.9 grams
What are the AIs for females (A) 9-13, (B) 14-18, (C) 19-50, (D) >50 years for: 1) 18:2n-6 2) 18:3n-3
(A) Females 9-13 1) 18:2n-6 = 10 grams 2) 18:3n-3 = 1.0 grams (B) Females 14-18 1) 18:2n-6 = 11 grams 2) 18:3n-3 = 1.1 grams (C) Females 19-50 1) 18:2n-6 = 12 grams 2) 18:3n-3 = 1.1 grams (D) Females >50 1) 18:2n-6 = 11 grams 2) 18:3n-3 = 1.1 grams
What are the AIs for males (A) 9-13, (B) 14-18, (C) 19-50, (D) >50 years for: 1) 18:2n-6 2) 18:3n-3
(A) Males 9-13 1) 18:2n-6 = 12 grams 2) 18:3n-3 = 1.2 grams (B) Males 14-18 1) 18:2n-6 = 16 grams 2) 18:3n-3 = 1.6 grams (C) Males 19-50 1) 18:2n-6 = 17 grams 2) 18:3n-3 = 1.6 grams (D) Males >50 1) 18:2n-6 = 14 grams 2) 18:3n-3 = 1.6 grams
In contrast to EPA, where in the body does DHA play a primary role?
- DHA has functional role in brain and retinal PPLs - DHA is critical to proper neuronal and retinal function -> major structural component of cerebrum and myelin sheath -> major FA of the retinal photoreceptor membranes
Functions of n-6 FAs: - what are the major functions of arachidonic acid (AA)?
- AA is major substrate for eicosanoid synthesis and signal transduction (via phosphatidylinositols) - membrane lipids are a source of precursors for the synthesis of important signalling molecules ______________________________ - Normally AA is high in membrane phospholipids - Can be used by the cell as a signalling molecule - Take home message = membrane lipids are a source of precursors for the synthesis of important signaling molecules
Why is the function of ALA (n-3) not that distinguishable from LA (n-6)?
- ALA needed in much smaller quantities - function of ALA is not distinguishable from LA, aside from role as precursor of EPA and DHA ___________________________________________________ - Is obvious that omega 6 are essential -> When you take them out of the diet you develop deficiency symptoms rapidly - But omega 3 are needed in less quantities which makes their functions not distinguishable from LA -> Share many of the same functions -> But omega 3 has a unique role in production of EPA and DHA and are less inflammatory - Many omega 6 FAs can take over some omega 3 functions if omega 3 intake low, but functionality is decreased (not ideal) - Eating more omega 3 = increase amount of omega 3 in membrane phospholipids = more omega 3 available for other functions (on next slide)
Is alpha linolenic acid (ALA) mainly converted to EPA or DHA?
- ALA to EPA = 8% (M) or 21% (F) - ALA to DHA = 0-4% (M) or 9% (F) - We don't form much DHA from dietary alpha linolenic acid (form more EPA) - We don't get much omega 3 in the diet in the first place and only a small amount of that is converted to EPA and DHA -> Thus it may be ideal to eat EPA and DHA in the diet
What groups are vulnerable to EFA deficiency?
- EFA deficiency usually due to dietary deficiency of LA (only 3-5 g/day needed to prevent deficiency) - may occur in infants fed very low fat diets or patients unable to eat (injury, major surgery with EFA-free TPN for extended periods)
EFA in tissues are contained primarily in what lipid form?
- EFA in tissues are contained primarily in phospholipids (PPLs) ________________________________________________ - availability of EFA in body is dependent on dietary intake of EFA -> therefore increased consumption changes membrane composition - modifying FA profile of PPLs results in modified structure and function
EPA COMPETES with AA for eicosanoid synthesis. What does this mean?
- EPA COMPETES with AA for eicosanoid synthesis -> including membrane incorporation, hydrolysis, and oxidative enzymes -> overall, EPA reduces the availability of AA in the phospholipid membrane and the metabolism of AA to n-6 eicosanoids - i.e. EPA is a poor substrate for COX but less eicosanoids are synthesized from AA -> therefore decreased eicosanoid response to cellular activation (i.e. decreased TXA2) ____________________________________________________________ From an Image - the synthesis of both AA and EPA requires enzymes ∆6 desaturase, elongase, and ∆5 desaturase - EPA also competes with AA in its incorporation into the membrane phospholipids - EPA competes with AA in metabolism by COX, LOX, and cytochrome P450
What effect can EPA/DHA have on inflammation?
- EPA/DHA can dampen the inflammatory response -> inflammatory mediators (IL-6, IL-1, and TNF-alpha) and produce less inflammatory eicosanoids (3 and 5 series)
What are the functions of eicosanoids?
- Extremely potent lipid mediators -> cause profound physiological effects at very dilute concentrations - Primarily act as local messengers, often via receptor mediated G-protein linked signaling pathways to affect: -> Inflammatory responses -> Blood flow and coagulation (vascular function) -> Smooth muscle contraction and relaxation -> Gut health and integrity - Cell-to-cell communication -> released into extracellular fluid -> endocrine & autocrine &/or paracrine mediators -> Both affect adjacent cells & act locally (where synthesized), but paracrine acts on other cells types, autocrine acts on same
Long term, what in the body can be used as biomarkers of FA intake or EFA status?
- FA composition of plasma lipids, platelet, RBCs, and adipose tissue can be used as biomarkers of FA intake or EFA status (long term) - LC-PUFAs are most abundant in plasma PPLs - cheek cell DHA and AA in PPLs have been correlated with DHA and AA in plasma, RBCs, and the diet -> excellent biomarker, especially in children
Functions of n-6 FAs: - what is the major function of linoleic acid (LA)?
- LA in specific sphingolipids prevents water loss from the skin -> deficiency results in epidermic breakdown
Which of these 3 sources can provide PUFAs?
- PUFAs = diet and/or elongation and desaturation reactions - however ALA and LA = ONLY DIET - ER FA elongation involves various eloyl enzymes, also utilizes malonyl CoA, NADPH, and fatty acyl CoAs as substrates
Describe the process of eicosanoid synthesis
- PUFAs are absorbed, transported/metabolized, and incorporated into PPLs - binding of a hormone or cytokine to plasma membrane - activation of phospholipase A2 (PLA2) -> cleaves PUFA (AA) from sn-2 position of PPL - FAs released from PPLs undergo oxidative reactions (mostly AA, but also GLA [20:3n-6], EPA, and DHA)
Why can the body not make the EFAs?
- We have ∆9 desaturases (can add a double bond to ∆9) but we do not have ∆12 or ∆15 desaturases in the body -> We can not add double bonds to the omega 3 or omega 6 position __________________________________________________________________ - No matter what we do to omega 3 or 6 FAs, they stay as omega 3 or 6s - when we elongate or shorten them it only occurs at the alpha end
What is the biomarker of EFA deficiency?* (2)
- accumulation of 20:3n-9 (eicosatrienoic acid or 'mean acid') and 22:3n-9 in tissues ______________________________________________ n-9 Series -> mean acid (20:3n-9) increases with EFA deficiency n-6 Series -> LA, AA, 22:4n-6, 24:4n-6, and 22:5n-6 increase with n-3 deficiency _________________________________________________ - LA (n-6) and ALA (n-3) essential -> EPA (20:5n-3) and DHA (22:6n-3) conditionally essential in infants - look at figure 18-2 in textbook
Which of these 3 sources can provide SFAs and MUFAs?
- all 3 - SFA and MUFAs = diet, DNL, and/or elongation reactions -> cytosol FA elongation occurs during DNL (FAS utilizes acetyl CoA and malonyl CoA to elongate FAs by 2 Cs = mostly 16:0 + some 14:0, 18:0)
What type of DRI are the fat DRIs?
- are adequate intakes (AIs) in grams per day - only infants have AI for total fat
High intake of EPA and DHA improves ...
- auto-immune diseases -> such as IBD and rheumatoid arthritis (decreased inflammatory mediators) - inflammation, oxidative stress, and amyloid plaque formation (animal studies) in Alzheimer's Disease - MI and stroke incidence, inflammatory mediators, hypertension and lipid profiles in metabolic syndrome, T2DM, and CVD - cancer cachexia -> decreases loss of weight and lean tissue, partly by decreasing inflammation
What is the function of PLA2 in eicosanoid synthesis?
- cleaves PUFA from sn-2 position of phospholipids
How do dietary lipids modify health?
- conversion to bioactive metabolites -> eicosanoids (inflammation) -> secondary messengers (PIP2) - modulation of transcription factor activity and gene expression -> ligands for transcription factors -> direct effects on genes - alteration of membrane composition and function -> fluidity, permeability, protein trafficking -> modify cell signal transduction -> lipid oxidation
What are some (2) n-3 specific clinical symptoms of deficiency?
- decreased visual acuity - peripheral neuropathy
FA elongases and desaturases are regulated/affected by several things. Provide some examples
- diet, hormones, development, chronic diseases -> diet (eating fish oils decreases activity) -> hormones (increased in women vs men) -> development/growth (increased) -> chronic diseases (decreased)
DHA in Normal Development - during the pre-natal period, how does the fetus receive FAs?
- during last trimester to 18 months DHA accumulates in neural tissues at a high rate - FAs transferred through the placenta from maternal blood (from diet/adipose tissue) -> passive diffusion therefore high accretion rate results in preferential transfer of LC-PUFAs ____________________________________________ - pre term infants have risk of AA and DHA deficiency b/c they miss last trimester of fat accumulation (do not have the EFA storage they need)
Define essential fatty acids (EFAs)
- fats that must be consumed in our diet b/c they cannot be synthesized in the body or b/c they cannot be synthesized in sufficient quantities
What are the major dietary sources of alpha-linolenic acid (ALA)?
- flaxseed, canola, and soybean oils - walnuts
How does acute and pathological inflammation differ?
- inflammation is essential for normal defense against pathogens and repair of tissue damage Acute Inflammation - immediate, well regulated response to injury - self limiting and resolves rapidly Pathological Inflammation - excessive activation and duration - insufficient regulation - peripheral tissue damage and systemic effects - component to many chronic diseases Sustained Inflammation - can cause tissue damage - may initiate / exacerbate atherosclerosis - can induce insulin resistance (disrupts insulin signalling) - impairs ability to defend against future infection
Note
- interest in omega-3 FAs has been fuelled by recent epidemiological analysis that places low intake of omega-3 FAs among the top 10 preventable causes of death in the US
Location of EFA (AA, DHA, or EPA) in PPLs are at what position(s)?
- location of EFA (AA, DHA, or EPA) in PPLs are at the sn-2 position (usually SFA at sn-1) ____________________________________________________________ - PPL Synthesis: esterification of an alcohol to phosphate of phosphatidic acid (1,2-diacylglycerol-3-phosphate) Recall: Phospholipids - sn-1 usually SFA - sn-2 usually UFA
Do longer chain lipids or shorter chain lipids play a more important role in gene expression regulation?
- longer chain metabolites = most potent effects, often by binding to transcription factors - many genes are regulated by highly unsaturated forms of EFAs - these include genes that control FA synthesis, mitochondrial and peroxisomal FA oxidation, SFA desaturation, synthesis of FA binding proteins, and insulin-mediated glucose utilization
What are the major dietary sources of arachidonic acid (AA)?
- meat - egg yolks
If an infant is n-3 deficient, how does the infant deal with the inadequate DHA intake?
- n-6 FA deficiency is rare (and evident) - if n-3 deficient, DHA is replaced by docosapentaenoic acid (DPA) (22:4n-6) -> changes retinal physiology, visual acuity, learning ability (but very difficult to detect)
In what way / why can n-6 FAs control the expression of your genes.
- n-6 FAs are ligands for transcription factors ____________________________________ - What you eat directly affects whether certain genes are expressed or not - High carb diet produces more insulin and glucose which affects gene expression (upregulates FA synthesis genes, etc.) - Omega 6 FAs and ligands for transcription factors - As ligands, they increase the expression of that gene
Is there a UL for fat intake?
- no
Can omega-3 and omega-6 FAs be interconverted?
- no - These 2 pathways do not interconvert - Can not make an omega 3 from an omega 6 and can not make an omega 6 from an omega 3 - And these pathways compete for enzymes (share the same enzymes)
Do infants require preformed DHA or can they convert LA and ALA into AA, DHA, and EPA?
- no conversion, but can function without preformed DHA (though not optimally) ________________________________________________________ - balance of DHA and AA required for normal function -> infants need preformed DHA in order to meet demand
What enzyme is especially important in eicosanoid synthesis?
- phospholipase A2 (PLA2)
Is the source of linoleic and alpha-linolenic FAs plant-based, animal-based, or can it be both?
- plant - Always a plant source for the essential fat (linoleic acid, alpha linolenic acid) -> Animals elongate and desaturate these into their longer chain derivatives (EPA, DHA, arachidonic acid)
What are the 2 major functions of PUFAs?
- required for 2 important physiological processes 1) synthesis of lipid biomediators 2) production of membrane phospholipids -> both structural and signal transduction properties - Lipids are important for sending messages between and within cells (biomediators, signal transduction) and have structural functions
Prostaglandins (PG)
- subtypes of EP receptors (a type of PG receptor) have different tissue distributions, are linked to different G proteins, and produce different functional responses - PG-mediated signalling is a very complicated process that occurs in different ways depending on the type of PG and the receptor to which it binds
What are the major dietary sources of linoleic acid (LA)?
- sunflower, corn, safflower, and canola oils
Does human breast milk contain DHA?
- yes Post-Natal - human breast milk contains DHA -> but adipose tissue both an energy source (e.g. for rapidly growing infant grey matter) and greater [DHA] per body weight than any other time in life
3) Would you expect to find an elevation in 20:3n-9 in the patient's plasma?
- yes (i think) n-9 Series -> mean acid (20:3n-9) increases with EFA deficiency n-6 Series -> LA, AA, 22:4n-6, 24:4n-6. and 22:5n-6 increase with n-3 deficiency - biomarker of EPA deficiency = accumulation of 20:3n-9 (eicosatrienoic acid or 'mead acid') and 22:3n-9 in tissues
Can the brain elongate/desaturate PUFAs?
- yes, but minimally - some brain cells elongate/desaturate PUFAs (but quantitatively low) -> majority of LC-PUFAs from liver synthesis -> transported in blood, enter brain (highly conserved, low turnover) _____________________________________________________________ - Some brain cells can elongate/desaturate PUFAs -> But majority come from liver -> Not much get transported into brain (highly conserved) -> That is why the brain does not use FAs for fuel
What are the AIs during lactation for: 1) 18:2n-6 2) 18:3n-3
1) 18:2n-6 = 13 grams 2) 18:3n-3 = 1.3 grams
What are the AIs during pregnancy for: 1) 18:2n-6 2) 18:3n-3
1) 18:2n-6 = 13 grams 2) 18:3n-3 = 1.4 grams
Main effects of gene expression regulation are via the activity of what 3 major classes of transcription factors?
1) PPARs 2) liver X receptor (LXR) 3) sterol regulatory element binding protein (SREBP) Examples: - SREBP inhibited form transport to nucleus by PUFAs, transcription, and SREBP1cmRNA stability regulated by n-3 FAs - EPA/DHA decrease gene expression (mRNA) levels of pro-inflammatory cytokines (i.e. TNF-alpha, IL-1, IL-6) - DHA binds and activates retinoid X receptor (RXR) which enables binding of transcription factors to PPAR, LXR, thyroid hormone receptor, vitamin D receptor, retinoic acid receptor
Phospholipids are continuously degraded and synthesized. What 2 types of enzymes accomplish this degradation and remodelling?
1) acyltransferases 2) phospholipases ___________________________________________ - PPL composition is organelle specific but also influenced by diet - PPLs are continuously degraded and synthesized -> head groups can be changed, as well as both fatty acyl groups (remodelling) - degradation and remodelling due to acyltransferases and phospholipases (specific for various positions) -> phospholipase A1 and A2 hydrolyze sn-1 and sn-2 FAs from PPLs (remodel acyl groups) -> phospholipase A2 important for release of AA from sn-2 position of membrane PPLs (-> eicosanoid synthesis)
What are the 5 nutritionally important n-3 PUFAs?
1) alpha-linolenic (ALA) 2) stearidonic acid (SDA) 3) eicosapentaenoic acid (EPA) 4) docosapentaenoic acid (DPA) 5) docosahexaenoic acid (DHA)
What are the 5 nutritionally important n-3 PUFAs, their N minus abbreviation, and typical sources? 1) alpha-linolenic (ALA) 2) stearidonic acid (SDA) 3) eicosapentaenoic acid (EPA) 4) docosapentaenoic acid (DPA) 5) docosahexaenoic acid (DHA)
1) alpha-linolenic (ALA) = 18:3n-3 - flaxseed oil, perila oil, canola oil, soybean oil, walnuts 2) stearidonic acid (SDA) = 18:4n-3 and 20:4n-3 - fish oils, genetically enhanced soybean oil, black currant seed oil, hemp oil 3) eicosapentaenoic acid (EPA) = 20:5n-3 - minor components in animal tissues 4) docosapentaenoic acid (DPA) = 22:5n-3 - fish, especially oily and cold water fish -> salmon, herring, anchovy, smelt, and mackerel 5) docosahexaenoic acid (DHA) = 22:6n-3 - fish, especially oily and cold water fish -> salmon, herring, anchovy, smelt, and mackerel ____________________________________ - Most important are alpha linolenic and EPA and DHA here - Not all nuts and seeds have omega 3, only a select few are high in them - Can of tuna has almost no fat so thus has almost no EPA and DHA Cold water and oily fish are high in EPA and DHA (EPA and DHA are highly kinked and still tend to be liquid in the freezer)
What are the major biological roles of lipids? (5)
1) barriers - LA in ceramides in the epidermic is critical to the structural integrity and barrier function of the skin 2) membranes - EFAs and their derivatives function in phospholiids to increase fluidity and permeability of cell membranes 3) structural components 4) lubricate surfaces 5) act as signalling molecules - eicosanoids are derivatives of EFAs and signaling molecules (such as steroids, vitamin D, cholesterol, and diacylglycerols) -> many of these lipids have EFAs as part of their structure
What are the 2 main pathways involved in eicosanoid synthesis?
1) cyclooxygenase (COX) = prostaglandins and thromboxanes synthesized via the cyclic pathway -> COX1 constitutive -> COX2 inducible 2) lipoxygenase (LOX) = leukotrienes by the linear pathway 3) cytochrome P450 -> another pathway in images but not in notes
What are the 3 sources of FAs in the body?
1) diet 2) de novo lipogenesis (DNL) (from carb and/or protein) 3) synthesis (elongation and desaturation of synthesized FAs)
What are the 4 major roles of n-6 PUFAs (from summary image)?
1) eicosanoids 2) phospholipids (PPLs) -> signal transduction 3) sphingolipids -> skin water barrier 4) PPARs (peroxisome proliferator-activated receptor) -> gene expression
What are the 3 conditionally essential FAs?
1) eicosapentaenoic acid (EPA) 2) docosahexaenoic acid (DHA) 3) arachidonic acid (AA) _______________________________________ - body can synthesize, but in limited quantities - EPA + DHA = omega 3 - AA = omega 6 ______________________________________ - Infant formulas used to only contain ALA and LA since it was thought that we could synthesize EPA, DHA, and AA in sufficient quantities at all stages of life But breast milk has EPA, DHA, and AA in it - Now realized that EPA, DHA, and AA are essential in infants and DHA and AA are added to most infant formula
1) What fatty acid would you expect to be deficient if a patient has skin epidermis breakdown? 2) What type of lipid is involved in this?
1) linoleic acid (18:2n-6) 2) sphingolipids - LA in specific sphingolipids prevents water loss from the skin -> deficiency results in epidermic breakdown
What are the 6 nutritionally important n-6 PUFAs?
1) linoleic acid (LA) 2) gamma-linolenic acid (GLA) 3) dihomo-gama-linolenic acid (DHGLA) 4) arachidonic acid (AA) 5) docosatetraenoic acid 6) docosapentaenoic acid
What are the 2 EFAs? (name + notation)
1) linoleic acid (LA) = 18:2n-6 2) alpha linolenic acid (ALA) = 18:3n-3
What are the 6 nutritionally important n-6 PUFAs, their N minus abbreviation, and typical sources? 1) linoleic acid (LA) 2) gamma-linolenic acid (GLA) 3) dihomo-gama-linolenic acid (DHGLA) 4) arachidonic acid (AA) 5) docosatetraenoic acid 6) docosapentaenoic acid
1) linoleic acid (LA) = 18:2n-6 - most vegetable oils and nuts 2) gamma-linolenic acid (GLA) = 18:3n-6 - evening primrose, borage, and black currant seed oils 3) dihomo-gama-linolenic acid (DHGLA) = 20:3n-6 - minor component in animal tissues 4) arachidonic acid (AA) = 20:4n-6 - animal fats, liver, egg lipids, fish 5) docosatetraenoic acid = 22:4n-6 - minor component in animal tissues 6) docosapentaenoic acid = 22:5n-6 - minor component in animal tissues ______________________________________ - Should know the names of these FAs, there N minus abbreviation, and typical sources - Most important to know are linoleic acid and arachidonic acid - If you are not eating enough omega 3 fats you are not making enough DHA so docosapentenoic acid is used in place of DHA (you function fine but not optimally)
What are the 4 classes of PPLs?
1) phosphatidylcholine -> most abundant -> structural importance, requires some dietary choline 2) phosphatidylethanolamine -> 2nd most abundant -> structural importance 3) phosphatidylserine -> 5-15% of PPLs (inner membrane - functional/signalling properties) -> increased in myeline (brain tissue -> increased DHA) 4) phosphatidylinositol -> <10% of PPLs -> relatively higher in brain tissue -> signalling and source of AA for eicosanoid synthesis (sn-1 = 18:0, sn-2 = 20:4n-6)
What are the (5) clinical symptoms of EFA deficiency?
1) scaly dermatitis (increased permeability to water and sebum production) 2) failure to grow in children 3) suppressed immune function 4) impaired reproduction 5) degeneration/impaired organ function
What are the AIs for infants 7-12 months for: 1) total fat 2) 18:2n-6 3) 18:3n-3
1) total fat = 30 grams 2) 18:2n-6 = 4.6 grams 3) 18:3n-3 = 0.5 grams
What are the AIs for infants 0-6 months for: 1) total fat 2) 18:2n-6 3) 18:3n-3
1) total fat = 31 grams 2) 18:2n-6 = 4.4 grams 3) 18:3n-3 = 0.5 grams
What length of n-3 and n-6 FAs are used to make eicosanoids?
= 20 carbons - 20 carbon versions of omega 3 and omega 6 FAs are used to make eicosanoids _________________________________________ - LA and ALA mostly plant sources - LC-PUFA animal and marine sources
What is the AMDR for total fat?
= 20-35% of daily energy intake (10-35% protein) (45-65% CHO)
What is the formula for arachidonic acid (AA)?
= 20:4n-6
What is the formula for eicosapentaenoic acid?
= 20:5n-3
What is the formula for docosahexaenoic acid (DHA)?
= 22:6n-3
Does EPA or DHA make prostaglandins, thromboxames, and leukotrienes (types of eicosanoids)?
= EPA
Major Functions of n-3 PUFAs: - What is the major n-3 precursor for eicosanoids?
= EPA (20:5n-3) -> antithrombotic and anti-inflammatory via competitive inhibition of AA metabolism -> oxygenated derivatives of EPA and DHA have potent anti-inflammatory effects (resolvins, protectins)
Would EPA be hypo- or hyper-triglyceridemic?
= EPA is hypotriglyceridemic (increase oxidation of TG in liver, partly via increased expression of PPAR)
What tissue and/or cell type do not synthesize eicosanoids?
= RBCs - eicosanoids synthesized by all mammalian cells except RBCs
What are the best 3 fish sources of EPA+DHA?
= cold water fatty fish - mackerel (2500 mg/100g) - herring (1700 mg/100g) - salmon (1200 mg/100g) - trout (500 mg/100g) - halibut (400 mg/100g) - tuna (400 mg/100g) - shrimp (300 mg/100g) - cod (300 mg/100g) Enriched Products - omega 3 eggs (75 mg/egg) - omega 3 pro eggs (125 mg/egg) - oasis juice (20 mg/serving) Supplements - usually around 300 mg/capsule
What type of lipid are prostaglandins, thromboxames, and leukotrienes?
= eicosanoids
What type of enzyme catalyzes the first rate limiting step in PUFA elongation and desaturation reactions?
= elongases - elongases catalyze 1st RLS, show subsrate specificity, tissue specific distribution, and regulation - FA elongases function with desaturases to generate many of the long chain MUFAs and PUFAs assimilated into cellular lipids thereby impacting cellular lipid composition and functions
Do males or females convert ALA into EPA and DHA more efficiently?
= females
What does PPAR stand for and what do they do?
= peroxisome proliferator-activated receptor - gene expression ____________________________________________________ - PPARs have a binding site for an omega 6 PUFA and a gene (FA oxidation) -> PPARs affect gene expression to increase FA oxidation as a result - Eat more omega 6 = increase FA oxidation in liver (good for fatty liver)
During what period of life is the [DHA] per body weight the highest?
= post-natal period (immediately after birth during breast feeding)
What area of the body, excluding adipose tissue, has the highest lipid content?
= the brain - after adipose tissue, brain has highest lipid content -> as components of PPLs, AA(n-6) and DHA(n-3) most abundant LC-PUFAs
How do AA and EPA/DHA differ in relation to their (anti)inflammatory properties?
AA = pro-inflammatory (PGE2, TXA2, LTB4) EPA + DHA = less potent or anti-inflammatory -> also produce resolvins and protectins (inflammation dampening, resolution promoting lipid mediators) __________________________________________ Recall: EPA - 3 series prostaglandins - 3 series thromboxanes - 5 series leukotrienes -> less biologically active (less inflammatory) than AA derived mediators AA - 2 series prostaglandins - 2 series thromboxanes - 4 series leukotrienes
EPA tends to make what types of eicosanoids? What about AA? What is the difference between the two?
EPA - 3 series prostaglandins - 3 series thromboxanes - 5 series leukotrienes -> less biologically active (less inflammatory) than AA derived mediators AA - 2 series prostaglandins - 2 series thromboxanes - 4 series leukotrienes - Eating more omega 6 (->AA) makes the 2 and 4 series versions which tend to be more inflammatory -> Do provide essential functions but not a good thing in chronic disease conditions where inflammation is a concern - DHA can be converted to docosatrienes, resolvins, and neuroprotectins which are anti-inflammatory _____________________________________ Eicosanoids = prostaglandins (2 or 3 series) = thromboxanes (2 or 3 series) = leukotrienes (4 or 5 series) = resolvins
A 4 year old girl who had persistent health problems since birth was referred to a pediatric genetic disease specialist for evaluation b/c of poor growth, ulcerated cornea, severe photophobia, scaly skin lesions, and cracking of the skin at the corners of her mouth. Analysis of her plasma revealed low levels of ARA and DHA A supplement of fish oil and black currant seed oil, which contains gamma-linolenic acid (18:3n-6) was prescribed This treatment corrected the deficiencies of ARA and DHA in the plasma and many of her symptoms gradually improved Biochemical studies revealed that the fatty acid ∆6-desaturase activity of her fibroblasts was very low 1) Why was black currant seed oil prescribed instead of corn oil as a source of n-6 PUFAs for this patient?
My Guess: - corn oil is a good source of linoleic acid (LA) (18:2n-6) - however, she needed more fully formed versions of omega-6 FAs since there was an issue with conversion for this patient, not with overall dietary intake of fat - Note: black currant seed oil is a good source of: -> gamma-linolenic acid (GLA) = 18:3n-6 -> stearidonic acid (SDA) = 18:4n-3
What is the PUFA range for typical north american diet vs AI range for adults (AMDR) 1) LA 2) ALA 3) n-6:n-3 ratio
Typical North American Diet 1) LA = >20 g/d 2) ALA = 1-3 g/d 3) n-6:n-3 ratio = 8:1 or 10:1 AI Range for Adults (AMDR) 1) LA = 12-17 g/d (5-10% energy) 2) ALA = 1.1-1.6 g/d (0.6-1.2% energy) 3) n-6:n-3 ratio = 5:1 (not based on AI) Note: American Heart Association recommends 900-1000 mg/day of EPA+DHA for people with CVD
