Fatty Acid Fatty Acid MetabolismMetabolism

Wolfgang Bayer, Wolfgang Bayer, Ph.D.Ph.D.

AK World Congress, May AK World Congress, May 2006,Vienna2006,Vienna

H2-C-OH + HOOC-(CH2)14-CH3

H-C-OH + HOOC-(CH2)14-CH3

H2-C-OH + HOOC-(CH2)14-CH3

glycerol palmitic acid

H2-C-OOC-(CH2)14-CH3

H-C-OOC-(CH2)14-CH3

H2-C-OOC-(CH2)14-CH3

triglycerid

Natural fats and oils are comprised of glycerol Natural fats and oils are comprised of glycerol esters of the higher even-numbered fatty acidsesters of the higher even-numbered fatty acids

= = triglyceridestriglycerides

- 3 H2O

Fat – what is it?Fat – what is it?

gly

cero

l

gly

cero

l

Pcholine

fatty acid 1

fatty acid 2

fatty acid 3

fatty acid 1

fatty acid 2

choline

P

fatty acid

sphingosine

P =phosphate

fatty acid

sphingosine

sugar

triglycerid phospholipid (phosphatidylcholin)

sphingolipid (sphingomyelin)

glycolipid (cerebrosid)

fatty acidsfatty acids

saturatedsaturated fatty acidsfatty acids

unsaturatedunsaturated fatty acidsfatty acids

monounsaturatedmonounsaturated fatty acidsfatty acids

polyunsaturatedpolyunsaturated fatty acidsfatty acids

ωω-3 fatty-3 fattyacidsacids

ωω-6 fatty-6 fattyacidsacids

Fatty acids - Fatty acids - nomenclaturenomenclatureWhat is the designation for this fatty What is the designation for this fatty acid?acid?

118

cis-9,12,15-octadecatrienoic acid

91215δ-endω-end

18:3, ω-3

α-linolenic acid

stearic acid, 18:0

saturatedsaturated

mono- mono- unsaturateunsaturatedd

poly- poly- unsaturateunsaturatedd

α-

oleic acid

linoleic acid,

αα-linolenic acid,-linolenic acid,

docosahexaenoic acid,

H3C CH3 H3C H

C C C C

H H H CH3

cis trans

Cis fatty acids are the naturally occurring Cis fatty acids are the naturally occurring forms of fatty acids.forms of fatty acids.

Trans fatty acids are produced when fats Trans fatty acids are produced when fats are hydrogenated (margarine). They have are hydrogenated (margarine). They have rigid structures and are described as rigid structures and are described as having atherogenic properties.having atherogenic properties.

Cis and trans fatty Cis and trans fatty acidsacids

Uptake and synthesis of fatty Uptake and synthesis of fatty acids (1)acids (1)

In the duodenum, nutritional fats (triglycerides) In the duodenum, nutritional fats (triglycerides) are split by lipases into monoglycerides and are split by lipases into monoglycerides and free fatty acids. Following absorption, free fatty acids. Following absorption, triglycerides are resynthesized, then triglycerides are resynthesized, then transported to tissues, or stored in fatty transported to tissues, or stored in fatty tissues, by means of chylomicrons.tissues, by means of chylomicrons.Fatty acids can be synthesized endogenously Fatty acids can be synthesized endogenously from glucose by means of the enzyme from glucose by means of the enzyme fatty acid fatty acid synthasesynthase (FAS). This process results in saturated (FAS). This process results in saturated fatty acids with up to 16 C atoms – palmitic acid fatty acids with up to 16 C atoms – palmitic acid (C 16:0). (C 16:0).

Uptake and synthesis of fatty Uptake and synthesis of fatty acids (2)acids (2)

Triglycerides can be synthesized from the fatty Triglycerides can be synthesized from the fatty acids produced in the liver. They enter the acids produced in the liver. They enter the bloodstream bound to VLDLs.bloodstream bound to VLDLs.

Fats are stored in fat cells (adipocytes), where Fats are stored in fat cells (adipocytes), where they are continuously built up and broken they are continuously built up and broken down. The amount of body fat is approx. 8-15 down. The amount of body fat is approx. 8-15 kg in men and 10-20 kg in women.kg in men and 10-20 kg in women.

Following reactions result in extended Following reactions result in extended saturated and monounsaturated fatty acids, saturated and monounsaturated fatty acids, but not in the poly-unsaturated C 18 fatty but not in the poly-unsaturated C 18 fatty acids (acids (ωω-3 and -3 and ωω-6).-6).

= coenzyme A

Fatty acid breakdown by ß-ß-oxidationoxidationThe fatty acid is The fatty acid is short-ened by 2 C short-ened by 2 C atoms in each atoms in each reaction cycle.reaction cycle.

Acetyl-CoA is prod-Acetyl-CoA is prod-uced, which can uced, which can then be then be metabolized to COmetabolized to CO22 and ATP in the and ATP in the citrate cycle.citrate cycle.

1 mol of palmitic 1 mol of palmitic acid produces 106 acid produces 106 mols of ATP, equiv-mols of ATP, equiv-alent to 3,300 alent to 3,300 kJ/mol.kJ/mol.

fatty tissue

fat lipolysis

fatty acids

plasmafatty acids

liver fatty acids

ß-oxidation

acetyl-CoA

ketogenesis

ketones

muscle ketones

acetyl-CoA

ox.phos.

ATP

ATP

Fatty acid breakdown and energy production

bowels triglycerides

split

fatty acids

Physiological functions of fatty acidsPhysiological functions of fatty acids

Energy pro-Energy pro-duction in duction in the the mitochondrimitochondriaaInsulation: Insulation: mechanicalmechanical, electrical, electrical

Building Building blocks of cell blocks of cell membranesmembranes

Eicosanoid Eicosanoid synthesis: synthesis: immunoregulatioimmunoregulation, regulation ofn, regulation of

vasotonus and brochotonus

Influence lipid metabolism, lower triglyceride Influence lipid metabolism, lower triglyceride levelslevels Regulate central nervous and sensory functionsRegulate central nervous and sensory functions Important during pregnancy: development of Important during pregnancy: development of foetal nervous system and brainfoetal nervous system and brain

αα-linolenic and linoleic acid, the basic -linolenic and linoleic acid, the basic components of the ω-3 and ω-6 fatty acids, components of the ω-3 and ω-6 fatty acids, cannot be synthe-sized by the human cannot be synthe-sized by the human organism.organism.

Omega-3 and omega-6 fatty Omega-3 and omega-6 fatty acidsacids

These are essential These are essential fatty acids that must be fatty acids that must be included regulary, in included regulary, in balanced amounts, in balanced amounts, in the diet. the diet. D.A.CH. D.A.CH. recommended ratio recommended ratio ωω--6/6/ωω-3: 5/1. -3: 5/1.

Ratio of Ratio of ωω-6 to -6 to ωω-3 fatty -3 fatty acidsacids

For further information: www.labor-bayer.de

Omega-3 and omega-6 fatty Omega-3 and omega-6 fatty acidsacids

Omega-3 and omega-6 fatty acids cannot Omega-3 and omega-6 fatty acids cannot be transformed into one another.be transformed into one another. Other longer-chained fatty acids can be Other longer-chained fatty acids can be made from made from αα-linolenic acid and linoleic acid -linolenic acid and linoleic acid by means of desaturation and elongation by means of desaturation and elongation steps. steps. (One reads this frequently in the literature – (One reads this frequently in the literature – but is it really true?)but is it really true?)

For further information: www.labor-bayer.de

oleic acidoleic acid 18:1, 18:1, ωω-9-9

linoleic acid18:2, ω-6

α-linolenic acid18:3, ω-3

δ-6-desaturase

18:2, ω-9γ-linolenic acid

18:3, ω-618:4, ω-3

elongation

20:2, ω-9dihomo-γ-linolenic

acid 20:3, ω-6 20:4, ω-3

δ-5-desaturase

eicosatrienoic acid20:3, ω-9

arachidonic acid20:4, ω-6

eicosapentaenoicacid 20:5, ω-3

elongation

22:5, ω-3

δ-4-desaturase

docosahexaenoic acid 22:6, ω-3

omega-9-series omega-6-series omega-3-series

eicosanoides eicosanoides eicosanoides eicosanoides eicosanoideseicosanoidesseries 1 series 2 series 3series 1 series 2 series 3PGE1,PGI1,TXA1PGE1,PGI1,TXA1 PGE2,PGI2,TXA2 PGE2,PGI2,TXA2 PGE3,PGI3,TXA3PGE3,PGI3,TXA3

LTB4, LTC4LTB4, LTC4 LTB5, LTC5LTB5, LTC5

anti-inflammatory

pro-inflammatory

1.1. ProstaglandinsProstaglandins can be produced in numerous can be produced in numerous tissues and posses tissue-specific effects, e.g. in tissues and posses tissue-specific effects, e.g. in enzymatic systems.enzymatic systems.

2.2. ProstacyclinsProstacyclins are produced in endothelial cells of are produced in endothelial cells of the blood vessels. They inhibit thrombocyte the blood vessels. They inhibit thrombocyte aggregation and dilate blood vessels.aggregation and dilate blood vessels.

3. 3. ThromboxanesThromboxanes, the antagonists of the , the antagonists of the prostacyclins, are produced in thrombocytes. They prostacyclins, are produced in thrombocytes. They lead to thrombocyte aggregation and stenosis of lead to thrombocyte aggregation and stenosis of blood vessels.blood vessels.

4. 4. LeukotrienesLeukotrienes are produced in leucocytes and are produced in leucocytes and other cells and contribute to allergic and other cells and contribute to allergic and inflammatory reactions.inflammatory reactions.

The eicosanoids

ω-6

ω-3

anti-inflammatory

pro-inflammatory

+ 9 g fish oil

+ 9 g fish oil

Omega-3 fatty acids and Omega-3 fatty acids and markers of inflammationmarkers of inflammation

James, M.J. et al.: James, M.J. et al.: Am. J. Clin. Nutr. Am. J. Clin. Nutr. 71, 343S-348S, 71, 343S-348S, 20002000

,,ωω-6-6

,,ωω-3-3

41 years old female patient, intake of 3 table-spoons flaxseed oil 5 times a week for months

Fatty acid statusFatty acid status