(isoprenoid chemistry will be covered separately)

Utilized in both plant & animal kingdom in the biosynthesis of
• fatty acids, fats & oils
• signaling molecules derived from FA such as prostaglandins
• anthraquinones and phenols found in certain botanicals
• polyketides such as macrolide antibiotics)
Initial assembly of 2C pieces

Fatty acid biosynthesis: reduction of carbonyls

Poly b
-keto esters can either be reduced to form fatty acids,
(as shown at left),
OR shuttled into the polyketide pathways, where they undergo cyclization reactions to form m-substituted phenolics or large macrocycles.

Fatty acids: Common long-chain carboxylic acids are shown in table 3.1
Some key points about fatty acid structure & properties:
1) The number of C in the chain is always even
Biosynthesis by the acetate pathway involves condensation of decarboxylated malonyl esters contributing 2C each
2) Saturated fatty acids of between 12 and 20 C are common; overall shape is straight-chain
3) Unsaturated fatty acids in nature are biosynthesized as cis (Z) isomers ; this puts a “kink” in the chains & affects 3-D structure
(trans-fatty acids only form synthetically)
4) As the number of double bonds increases (polyunsaturated fatty acids) melting points decrease

Where does the unsaturation come from?

Common end products from fatty acids
Fats & oils (TAGs)
– energy storage
Phospholipids
- cell membranes

Triacylglycerols (TAG, aka “triglycerides”)
H
2
C
OH
HOOC R
1
H
2
C
O
O
C
O
R
1
HC
H
2
C
OH
OH
+ HOOC R
2
HOOC R
3
HC
H
2
C
O
O
O
C
C
R
3
R
2
Condensation of glycerol with three fatty acids produces a molecule of fat or oil (FA may vary within a TAG)
Some key points about structure and properties of triacylglycerols
1) TAG that are solid at room temperature are classified as fats (animalbased)
2) TAG that are liquid at room temp. are classified as oils (vegetablebased)
3) In general, the more unsaturated the FA in a TAG, the less solid it is
4) Most liquid TAG come from plant sources (olives, corn, safflower)
5) Most solid or primarily saturated fats come from animal sources
6) 3-D structure of FA affects packing which then affects melting point
Trans fatty acid is similar in shape to a saturated fatty acid
TAGs composed of mostly unsaturated FA do n’t pack as tightly due to shape
Table 3.2 of Dewick: Fatty acid composition of some common oils and fats from plant sources

Triacylglycerols (TAG, aka “triglycerides”)
H
2
C
OH
HOOC R
1
H
2
C
O
O
C
O
R
1
HC
H
2
C
OH + HOOC R
2
HOOC R
3
HC O
O
C
R
2
OH
H
2
C
O C
R
3
Condensation of glycerol with three fatty acids produces a molecule of fat or oil (FA may vary within a TAG)
Chemistry of TAG: a) Saponification:
Base-catalyzed hydrolysis (NaOH) produces fatty acid salts + glycerol
2) TAG that are liquid at room temp. are classified as oils (vegetableb) Hydrogenation:
Reaction with H
2
/Pt converts unsaturated carbons to saturated
3) In general, the more unsaturated the FA in a TAG, the less solid it is c) Catabolism: TAG undergo acid-catalyzed hydrolysis in stomach
(digestion) Fatty acids are broken down 2 C at a time to acetyl-CoA which enters citric acid cycle
5) Most solid or primarily saturated fats come from animal sources d) Lipid peroxidation
6) 3-D structure of FA affects packing which then affects melting point and antioxidants oxidized by O
2
Polyunsaturated fatty acids are easily
or oxygen free radicals:
Trans fatty acid is similar in shape to a peroxy radical
TAGs composed of mostly unsaturated FA don’t pack as tightly due to shape an alkyl hydroperoxide
Health ramifications: Oxidation of LDL initiates formation of “plaque”
(solid buildup) in blood vessels and onset of atherosclerosis/heart disease.
Fatty acids are a major component of:
 Lipoproteins, especially LDL (low-density lipoproteins)
 Cell membranes--oxidation degrades membranes making them less fluid
 Oils and fats in food; oxidation causes “rancidity”
Antioxidant compounds react with free radicals (often by forming a more stable free radical) and remove them from the site before damage occurs.
Common antioxidants include substituted phenols, vitamins E, A
C
&

Chemistry of TAG: a) Saponification:
Base-catalyzed hydrolysis (NaOH) produces fatty acid salts + glycerol b) Hydrogenation:
Reaction with H
2
/Pt converts unsaturated carbons to saturated c) Catabolism: TAG undergo acid-catalyzed hydrolysis in stomach
(digestion) Fatty acids are broken down 2 C at a time to acetyl-CoA which enters citric acid cycle d) Lipid peroxidation and antioxidants
Polyunsaturated fatty acids are easily oxidized by O
2
or oxygen free radicals: a peroxy radical an alkyl hydroperoxide
Health ramifications:
Oxidation of LDL initiates formation of “plaque”
(solid buildup) in blood vessels and onset of atherosclerosis/heart disease.
Fatty acids are a major component of:
 Lipoproteins, especially LDL (low-density lipoproteins)

Cell membranes--oxidation degrades membranes making them less fluid
 Oils and fats in food; oxidation causes “rancidity”
Antioxidant compounds react with free radicals (often by forming a more stable free radical) and remove them from the site before damage occurs.
Common antioxidants include substituted phenols, vitamins E, A & C

Chemistry of TAG: a) Saponification:
Base-catalyzed hydrolysis (NaOH) produces fatty acid salts + glycerol b) Hydrogenation:
Reaction with H
2
/Pt converts unsaturated carbons to saturated c) Catabolism: TAG undergo acid-catalyzed hydrolysis in stomach
(digestion) Fatty acids are broken down 2 C at a time to acetyl-CoA which enters citric acid cycle d) Lipid peroxidation and antioxidants
Polyunsaturated fatty acids are easily oxidized by O
2
or oxygen free radicals: a peroxy radical
Oxidation of fatty acids causes problems with
• Lipoproteins – oxidation of the lipids causes dysfunction, induces an inflammatory response
(solid buildup) in blood vessels and onset of atherosclerosis/heart disease.
• Cell membranes – oxidation degrades membranes, making them

Lipoproteins, especially LDL (low-density lipoproteins)
 • Food shelf life – oxidation of oils and fats in foods causes

“rancidity”
Antioxidant compounds react with free radicals (often by forming a more stable free radical) and remove them from the site before damage occurs.
Common antioxidants include substituted phenols, vitamins E, A & C

Dietary fat and the human body
Fats and cholesterol (in the form of fatty acid esters) are carried through the bloodstream and distributed to and from the tissues and organs by lipoproteins
LDL: Low density lipoproteins carry cholesterol from liver to tissues
High LDLs tend to deposit more lipid in blood vessels
Lipids are subject to oxidation (see previous page)
High LDL levels raise risk of atherosclerosis and heart disease
HDL: High density lipoproteins carry cholesterol back to the liver
They tend to scavenge lipids left behind
High HDL levels lower cardiovascular disease risk
Effects of dietary fatty acids on serum cholesterol levels:
Mono (MUFA) and polyunsaturated (PUFA): lower LDL/ raise HDL
Saturated fats: raise both LDL and HDL
Trans-fats (processed food): raise LDL
Omega3’s (highly unsaturated) lower LDLs, raise HDLs

Dietary fat and the human body
Fats and cholesterol (in the form of fatty acid esters) are carried through the bloodstream and distributed to and from the tissues and organs by lipoproteins
LDL: Low density lipoproteins carry cholesterol from liver to tissues
High LDLs tend to deposit more lipid in blood vessels
Lipids are subject to oxidation (see previous page)
High LDL levels raise risk of atherosclerosis and heart disease
HDL: High density lipoproteins carry cholesterol back to the liver
They tend to scavenge lipids left behind
High HDL levels lower cardiovascular disease risk
Major sources of:
Saturated FA: meat, poultry and dairy products
MUFA/PUFA: plant-based oils, fish oil omega-3 FA: Fish oil (18% EPA, 12% DHA)
Algae (40-50% DHA)
Flaxseed oil (50-60% ALA) trans-FA: partially hydrogenated oils
Effects of dietary fatty acids on serum cholesterol levels:
Mono (MUFA) and polyunsaturated (PUFA): lower LDL/ raise HDL
Saturated fats: raise both LDL and HDL
Trans-fats (processed food): raise LDL
Omega3’s (highly unsaturated) lower LDLs, raise HDLs

• “Omega” system: position of C=C are counted from methyl end of chain
• w
-3 fatty acids: a
-linolenic, DHA, EPA
• found mainly in fish, nuts, seeds and seed oils
Why fish? See http://marinelife.suite101.com/article.cfm/why_do_fish_have_omega3_fatty_acids
• w
-3 are good for your health!
• w
-6 fatty acids are more common in Western diet
• Most omega-3’s are highly unsaturated, and they improve the lipoprotein ratio (HDL:LDL)
• Omega-3’s believed to reduce inflammation throughout the body (see prostaglandins and precursors) by competitive inhibition of enzymes used in production of
PG 2-series prostaglandins (the really bad ones)

• According to Environmental Defense Fund website, wild
Alaskan salmon are the best choice, relatively free of contaminants
• Canned salmon is a cheaper choice, but safe because it’s mainly sockeye or pink from Alaska. Omega-3 content was slightly lower.
• Farmed salmon is an Eco-Worst choice. Atlantic salmon are usually farmed in large-scale, densely stocked netpens that pollute surrounding waters with waste and chemicals. Despite a higher omega-3 content, EDF recommends the following due to elevated PCBs levels:
• Adults & kids 6-12 should eat no more than 1 meal per month
• Kids up to age 6 should eat no more than ½ meals per month
• http://www.edf.org/page.cfm?tagID=15802

• A 2003 report from the Environmental Working Group showed that farmed salmon in the U.S. has the highest levels of PCBs.
• A widely publicized study in Science (January 2004) suggested that farmed Atlantic salmon had higher levels of PCBs and other toxics
(mercury) than wild Pacific salmon.
• Amid public concern, the importation of farmed Atlantic salmon to the
United States went down by 20 percent in early 2004.
• Subsequent research has found that the health benefits of both farmed and wild salmon exceed potential risks, said Eric Rimm, associate professor of epidemiology and nutrition at the Harvard
School of Public Health.
• Rimm was a co-author of a study in the Journal of the American
Medical Association in 2006 that said the PCB levels in farmed salmon were not a cause of concern compared with the benefits.
• "It's clear that if there is any risk, the benefit is still 300 to 1,000 times greater from the fact that you're getting the omega-3s," he said.
As quoted in Landau, Farmed or wild fish: Which is healthier? (CNN Health) http://www.cnn.com/2010/HEALTH/01/13/salmon.farmed.fresh/index.html

Fish omega-3 content
Farmed Atlantic salmon per 100 g serving
1.73 g
Wild Alaskan salmon
Bluefin tuna
Swordfish
Rainbow trout
Canned white albacore tuna
Steelhead trout
Shrimp (giant tiger)
Squid (longfin)
Halibut
Yellowfin tuna (ahi)
Alaskan cod
Sea scallops (US/Canada)
Atlantic cod
1.4 g
1.17 g
1.0 g
1.0 g
0.95 g
0.60 g
0.49 g
0.49 g
0.42 g
0.23 g
0.21 g
0.19 g
0.18 g
For comparison: walnuts have
10.4 g of w
-3 per
100g serving, but no EPA or DHA
Source: http://www.edf.org/page.cfm?tagID=1540

• Animal study: rats supplemented with E-EPA (vs. palm oil) showed better levels of neuro-transmitter acetylcholine, improved memory
• Babies who consumed formula supplemented with DHA had better vision by 1 yr of age
• In vitro studies show inhibition of oral microbial pathogens
• Japanese study showed elderly with higher dietary intake of DHA had significanly lower incidence of periodontal disease – linked to antiinflammatory
• Patients with metastatic breast cancer taking DHA during chemotherapy survived longer
• Chemistry matters: ALA has some heart benefits, but longer-chain EPA, DHA more effective in most studies

Sara Lee targets kids with low-dose DHA omega-3 bread
By Shane Starling, 16-Feb-2010
Related topics: Nutritional lipids and oils, Cardiovascular health, Cognitive and mental function, Eye health
Illinois-based food multinational, Sara Lee, has made its first leap into the functional bakery, omega-3 space with a DHA-fortified white bread aimed at children that has been backed by the Disney Corporation.
The bread that retails at the same pricing range ($2.39 to $3.49) as the rest of the Soft & Smooth range it has joined, is fortified with
12mg of DHA (docosahexaenoic acid) supplied by global DHA market leader, Martek Biosciences Corporation.
It will be distributed nationally in grocery stores and coupons for it will be available on selected Disney websites.
Sara Lee spokesperson, Gina Raeber, told NutraIngredients-USA.com Sara Lee arrived at the level of 12mg per two-slice serving because at higher levels taste and texture came into play.
“We were not on the absolute limit at 12mg but that was a level we felt could significantly contribute to DHA intakes,” she said.
“This product will appeal to mums as children begin to consume whole foods.”
Sara Lee Soft & Smooth Plus Made with DHA Omega-3 comes in two versions - 100% Whole Wheat and Made with Whole Grain
White. The world’s most successful omega-3 bread, ‘Tip Top Up Omega-3 DHA’, sells in Australia and similarly targets children’s brain health, but contains 32mg of fish-sourced DHA per twoslice serving. Martek’s DHA is vegetarian and algae-sourced.
The US Institute of Medicine recommends DHA intakes of 70mg for 1-3 year-olds; 90mg for 4-8 year-olds; and 120mg for 9-13 yearolds, meaning Sara Lee’s bread comes in at about 10 per cent of the suggested intake for pre-teens and more for younger infants.
It is estimated the average US child consumes between 30 and 40mg of DHA per day.
A website set up to back the product, in conjunction with a Facebook page, states: “Based on a growing body of scientific evidence, docosahexaenoic acid (DHA) Omega -
3 helps to support healthy brain development.”
Sara Lee said the statement had been cleared with the Food and Drug Administration.
Of the dosage level, Frances-Kelly observed:
“The idea is to introduce life’sDHA to family diets in a variety of ways – breads, yogurts, juices, milks – so that at the end of the day the consumer is able to conveniently add DHA to their diet in a way that really adds up and provides brain, eye and heart benefits.”
In a statement, Tim Zimmer, vice president of Sara Lee North American Fresh Bakery said: “We understand the need to ensure proper nutrition through all stages of life especially in younger children. Bread with DHA Omega-3 is an excellent and simple way to provide moms with a greattasting, nutritious option their little ones will love.”

natural CLA is mostly cis-9, trans-11-octadecadienoate
• Formed in ruminants from LA through microbial biohydrogenation or from trans-vaccenic acid in tissues by
D
-9 desaturase
• Position and stereochem of isomers varies
• Produced commercially by base-catalyzed isomerization of LA in plant oils
• Growing list of potential health-promoting effects include:
– antidiabetic effects and reduced body fat (suppression of
FA synthesis and enhanced metabolism seen in rats)
– antiinflammatory properties
– anti-cancer effects in mice (skin, colon)
– reduction of atherosclerosis, blood pressure
– immune-enhancement

Science: Slimming ingredients beyond satiety
By Stephen Daniells, 21-Jan-2010
In the third part of our series on weight management, NutraIngredients looks at how nutritional approaches may boost body-shaping, and how our gut microflora may be the future of weight management.
Body sculpture
An area garnering interest is in ‘body-shaping’. A stand-out ingredient is CLA (conjugated linolenic acid), a fatty acid naturally present in ruminant meat and dairy products.
Supplements available commercially include Tonalin and Clarinol. Both ingredients have numerous studies supporting their potential in the weight management arena. Indeed, a human clinical trial using Clarinol ( Int. J. Obes ., 2007, Vol. 31, pp. 1148-54) reported an increase in lean body mass of about 0.4 kg in the CLA group, over the placebo group. Interestingly, fat mass reduction was localized at the abdomen and the legs. This gives credence to the ingredient's promotional claims to be a body shaper.
The mechanism of action has been well studied: If fat consumed is not used for energy, the triglycerides are taken up by fat cells a mechanism for which the enzyme lipoprotein lipase is responsible. CLA inhibits this enzyme, and instead the triglycerides are diverted to the muscle cells to be burnt. Here the CLA induces the activity of another enzyme, carnitine palmitoyl transferase, which is responsible for oxidation and the burning of fat.

Bioactivities of the prostaglandins
• contraction and relaxation of smooth muscle (uterus, cardiovascular system, intestinal tract, lungs)
• inhibit gastric acid secretion
• control blood pressure and suppress blood platelet aggregation
• second messengers, modulate hormone stimulation and metabolic response
• produce inflammation

Formation of prostaglandins and prostacyclins:
Role of COX

Prostaglandin precursors

Thromboxanes
Activity of TXA
2
>> TXB
2
• Blood platelet aggregation  forming a clot or thrombus
• increases cytoplasmic calcium concentrations
• opposite effect to PGI
2
; thrombosis may be due to imbalance in the two activities

Leukotrienes are involved in allergic responses and inflammatory processes.
An antigen –antibody reaction  release of histamine or slow reacting substance of anaphylaxis (SRSA) which mediate hypersensitive reactions like asthma, hay fever
SRSA = a mixture of LTC4, LTD4, LTE4

From Simopoulos, A. (2002) Omega-3 Fatty Acids in Inflammation and
Autoimmune Diseases. J. Am. Coll. Nutr.
21: 495-505.
• Among the fatty acids, the omega-3 polyunsaturated fatty acids
(PUFA) possess the most potent immunomodulatory activities.
• Among omega-3, those from fish oil (EPA and DHA) are more biologically potent than ALA.
• Some of the effects of omega-3 PUFA are brought about by modulation of the amount and types of eicosanoids made.
• Other effects come from eicosanoid-independent mechanisms: actions upon intracellular signaling pathways, transcription factor activity and gene expression.
• Animal experiments and clinical intervention studies indicate that omega-3 fatty acids have anti-inflammatory properties that might be useful in managing inflammatory and autoimmune diseases.

From Simopoulos, A. (2002) Omega-3 Fatty Acids in Inflammation and
Autoimmune Diseases. J. Am. Coll. Nutr.
21: 495-505.
• Coronary heart disease, major depression, aging and cancer are characterized by an increased level of interleukin 1 (IL-1), a proinflammatory cytokine.
• Many autoimmune diseases (arthritis, Crohn’s, colitis, lupus) are characterized by high levels of IL-1 and proinflammatory LTB acids.
4
- produced by omega-6 fatty
• Clinical trials have assessed the benefits of dietary fish oils in inflammatory and autoimmune diseases (RA,
Crohn’s, colitis, psoriasis, lupus, MS, migraine)
• Many trials of fish oil in chronic inflammatory diseases reveal significant benefit, including decreased disease activity and a lowered use of anti-inflammatory drugs.

From Simopoulos, A. (2002) Omega-3 Fatty Acids in Inflammation and
Autoimmune Diseases. J. Am. Coll. Nutr.
21: 495-505.

• Biosynthesis: Dewick, Medicinal Natural Products, Chapter 3
(Acetate Pathway)
• General information and chemistry in functional foods:
Dobson, G. “Chapter 2: Analysis of Fatty Acids in Functional
Foods with Emphasis on w3 FA and Conjugated LA” in
Methods of Analysis for Functional Foods and Nutraceuticals,
2 nd edition, Hurst, ed., CRC Press, 2008
• w-3 FA and inflammation: Simopoulos, A. (2002) Omega-3
Fatty Acids in Inflammation and Autoimmune Diseases. J.
Am. Coll. Nutr.
21: 495-505.
• Recent findings on health benefits: Nutra handouts and www.nutra Ingredients-usa.com
• Analysis methods – “Basic Food Composition Analysis Part 2” and Nielsen, S. Food Analysis, 3 rd Edition, Kluwer, 2003:
Chapters 8 and 14 on crude fat analysis and characterization