Lipids

Prof.Dr.Gülden Burçak2011-2012

• Heterogenous group • Insoluble in water, soluble in nonpolar solventsDietary constituentsAdipose tissueMyelinated nervesLipoproteins• Obesity, diabetes mellitus, atherosclerosis

1)Simple lipids Fats Waxes 2)Complex lipids Phospholipids Glycolipids (glycosphingolipids) Sulfolipids,aminolipids,lipoproteins 3)Precursor and derived lipids Fatty acids, glycerol, steroids, other alcohols, fatty aldehydes, ketone bodies, hydrocarbons, lipid-soluble vitamins, hormones

Simple lipids• Fats : Esters of fatty acids with

glycerol A fat in the liquid state : oil• Waxes :Esters of fatty acids with

higher molecular weight monohydric alcohols

• Uncharged lipids are called neutral lipids

AcylglycerolsCholesterolCholesteryl esters

Fatty acids• Esterified and unesterified• Even numbered, straight-chain

derivatives• Saturated and unsaturated

Nomenclature• -oic, -anoic, -enoic• Numbered from the carboxyl carbon

(carbon no 1)• α, ß, γ……………..ω ( terminal CH3

carbon)• ∆ : number and position of double

bonds• ∆9 : double bond between C 9 and

C10• ω9 :double bond on C 9 counting

from the ωC ; ω9, ω6, ω3

Saturated fatty acids

Unsaturated fatty acids• 1)Monounsaturated• 2)Polyunsaturated• 3)Eicosanoidsderived from eicosa (20C) polyenoic

fatty acids : prostanoids,leukotrienes and lipoxins

Oleic acid

Essential fatty acids• Linoleic acid (ω-6) • α-Linolenic acid (ω-3) • Arachidonic acid (ω-6) can be

formed from linoleic acid.

Geometric isomerism

• Naturally occuring unsaturated fatty acids • are nearly all of cis configuration• L-shaped• A high number of cis double bonds leads to a

variety of possible spatial configurations Arachidonic acid with four cis double bonds has

kinks or U shape Spatial relationships in plasma membrane

phospholipids are important Trans fatty acids disturb the spatial relationships

• Melting pointChain lengthDegree of unsaturation• Membrane lipids are more

unsaturated than storage lipids.

Eicosanoids• Parent compound :C20 polyunsaturated fatty acids• Physiologically and pharmacologically active

compounds Prostanoids• prostaglandins (PGs) • prostacyclins (PGIs)• thromboxanes (TXs) Leukotrienes (LTs) Lipoxins (LXs)

• Prostaglandins cause contraction of smooth muscle cells

• Prostacyclins are potent inhibitors of platelet aggregation

• Thromboxanes cause vasoconstriction and platelet aggregation

• Leukotrienes and lipoxins are potent regulators of many disease processes

• Leukotrienes are potent proinflammatory agents

Prostaglandin E2

Thromboxane A2

Leukotriene A4

Triacylglycerols : Storage

1,3-Distearopalmitin

Mixed triacylglycerol

Phospholipids1) Phosphatidic acid and phosphatidyl

glycerol2) Phosphatidylcholine3) Phosphatidylethanolamine4) Phosphatidylinositol5) Phosphatidylserine6) Lysophospholipids7) Plasmalogens8)Sphingomyelins

Phosphatidic acid

Phosphatidylcholines

• Most abundant in the plasma membrane• Saturated acyl radical in C1 position and

unsaturated in the C2

• Choline: hepatic lipoprotein synthesis and export ; acetyl choline

Dipalmitoyl lecithin• Surface-active agent (surfactant) in

the lung• Alveolar walls are not strong enough

to maintain their shape against the surface tension of water.

• Dipalmitoyl lecithin and sphingomyelins secreted to the lung chamber prevent the adherence of the inner surfaces of the alveoli

• Respiratory distress syndrome

Phosphatidylserine

Phosphatidylethanolamine

Phosphatidylinositol

Phosphatidylinositol 4,5-bisphosphate : a precursor of second messengers

Diphosphatidylglycerol (Cardiolipin)

Mitochondrial membranes

Lysolecithin

• Lysophospholipids : important in the metabolism and interconversion of phosholipids.

• Phospholipase A2 : formation of a lysophospholipid

Plasmalogens

• Brain and muscle tissue

Sphingomyelins

• Brain and nerve tissue

Glycolipids• In cell surface carbohydrates• Particularly in the nervous tissue• GlycosphingolipidsGalactosylceramide : neural tissuesGlucosylceramide : extraneural

tissues

Galactosylceramide (Galactocerebroside)

• Brain and other nervous tissue

• C24 : lignoceric, cerebronic , nervonic , oxynervonic acids

• Sulfogalactosylceramide (sulfatide) : myelin

Fatty acids in cerebrosides

Gangliosides• Complex glycosphingolipidsGlucosylceramide + one or more

sialic acids• Nervous tissue

Sialic acid : N-acetyl neuraminic acid

Neuraminic acid : 9 C sugar derived from mannosamine and pyruvate

GM1 ganglioside : Monosialoganglioside

Steroids• The sterane ring

Cyclopentanoperhydrophenanthrene, a tetracyclic hydrocarbon

• Steroid nucleus

Chair and boat conformation

Cis-trans configuration

Cholesterol

• Widely distributed in all cells, particularly in the nervous tissue

• Plasma membrane and lipoproteins• In animal fats• Reduction of double bond : coprostanol

(coprosterol)

Esterification of cholesterol at C3

Cholic acid : A cholesterol derivative

Steroid hormones

Ergosterol

A precursor of vitamin D

Isoprene and polyprenoids : dolichol, ubiquinone

C95 alcohol

Plant derived isoprenoids• Fat soluble vitaminsVitamin AVitamin D Vitamin EVitamin K

Adult reference ranges for lipids

• Total cholesterol : 140-200 mg/dL• HDL cholesterol : 40-75 mg/dL• LDL cholesterol : 50-130 mg/dL• Triglycerides : 60-150 mg/dL• Of total fatty acids 45 % in triglycerides, 35% in

phospholipids 15% in cholesterol esters and 5% as free fatty acids.

A lipoprotein molecule

Classification of plasma lipoproteins

Lipid Peroxidation

• Autooxidation of polyunsaturated fatty acids (methylene interrupted double bonds)

• Initiated by free radicals,light, metal ions, heme compounds, lipoxygenases

• ROO• , RO• and OH• radicals• Deterioration of foods• Tissue damage

Lipid peroxidation is a chain reaction

• Naturally occuring antioxidants vitamin E, uric acid, vitamin C, beta carotene

• Catalase and peroxidases ; preventive• Vitamin E and superoxide dismutase ; chain

breaking, trapping ROO• and O2⁻•

• Food additives : propyl gallate, butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT)