Utilized in both plant & animal kingdoms in the biosynthesis of fatty acids (FA), fats & oils signaling molecules derived from FA such as prostaglandins anthraquinones and phenols found in certain botanicals polyketides, such as macrolide antibiotics) Acetate Pathway: Production of fatty acids, polyketides and m-oxygenated aromatics

Initial assembly of 2C pieces uses a series of Claisen condensations Fatty acid synthase is an enzyme complex that controls the condensation of acetyl-CoA building blocks onto a starter unit

Fatty acid biosynthesis: Poly-  -keto chains destined to become fatty acids are shuttled into reductive pathway, where C=O are reduced to CH 2

Where does the unsaturation come from?

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

Table 3.2 of Dewick: Fatty acid composition of some common oils and fats from plant sources

Oxidation of fatty acids causes problems with Lipoproteins – oxidation of the lipids causes dysfunction, induces an inflammatory response Cell membranes – oxidation degrades membranes, making them less fluid and flexible Stability/shelf life – oxidation of natural oils and fats causes “rancidity”

Omega classification of fatty acids: structure and health effects “Omega” system: position of C=C are counted from methyl end of chain  -3 fatty acids:  -linolenic, DHA, EPA found mainly in fish, nuts, seeds and seed oils Why fish? See life.suite101.com/article.cfm/why_do_fish_have_omega3_fatty_acidshttp://marine- life.suite101.com/article.cfm/why_do_fish_have_omega3_fatty_acids  -3 are good for your health!  -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)

Recent findings on omega-3 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

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:

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 4 - produced by omega-6 fatty acids. 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:

Prostaglandins and related signaling molecules Bioactivities of the prostaglandins contraction and relaxation of smooth muscle (uterus, cardiovascular, 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

Unusual fatty acids are found among some families 1)Modifications on the chain post-synthesis can lead to rings, alkyne groups 2)Use of unusual starter units as a basis for growing chain

Acetylenic fatty acids

Alkylamides found in Echinacea purpurea are derived from acetate pathway

Unusual starter units lead to complex molecules many steps flavonoids and stilbenes 2 isoprenes