3. LIPIDS3. LIPIDS

Medical BiochemistryMedical BiochemistryMolecular Principles of Structural Organization of CellsMolecular Principles of Structural Organization of Cells

LIPIDSLIPIDS• Organic compounds of biological natureOrganic compounds of biological nature• Due to the predominence of hydrocarbon chains in their structure (-CHDue to the predominence of hydrocarbon chains in their structure (-CH22--CHCH22-CH-CH22-), they have a -), they have a hydrophobichydrophobic nature which explains why nature which explains why

– they are they are insoluble or poorly soluble in waterinsoluble or poorly soluble in water and and – soluble in nonpolar solventssoluble in nonpolar solvents (chloroform, ether, benzene). (chloroform, ether, benzene).

Classification:Classification:• depending on their physico-chemical properties (polarity):depending on their physico-chemical properties (polarity):

– neutral, nonpolar (with no charge)neutral, nonpolar (with no charge)– polar (charged)polar (charged)

• depending on physiological importance:depending on physiological importance:– reserve – stored, used to supply energetic needs (acylglycerides)reserve – stored, used to supply energetic needs (acylglycerides)– structural – used to buildup the biological membranes, protective layers in structural – used to buildup the biological membranes, protective layers in plants, insects, skin of vertebrates; plants, insects, skin of vertebrates;

LocationLocation: lipids represent 10-20% of the body mass (10-12 Kg) of which : lipids represent 10-20% of the body mass (10-12 Kg) of which – 98% is the reserve in the fat tissue,98% is the reserve in the fat tissue,– structural lipids (2-3 Kg) exist in membranes (40% of the dry weight); the richest structural lipids (2-3 Kg) exist in membranes (40% of the dry weight); the richest tissue in lipids is the nervous tissue (20-25%)tissue in lipids is the nervous tissue (20-25%)

COMPONENTS OF LIPIDSCOMPONENTS OF LIPIDS1. FATTY ACIDS (FA)1. FATTY ACIDS (FA)

FA are derivatives of aliphatic hydrocarbons that contain FA are derivatives of aliphatic hydrocarbons that contain – COOH– COOH H H H H H H H H H H H H H H H H HH H H H H H H H H H H H H H H H H ll ll ll l l l l l l l l l l l l l l ll l l l l l l l l l l l l H - C – C – C – C – C – C – C – C – C – C – C – C – C – C – C – C – C – H - C – C – C – C – C – C – C – C – C – C – C – C – C – C – C – C – C – COOHCOOH ll ll ll l l l l l l l l l l l l l l ll l l l l l l l l l l l l H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H H

CHCH33-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22-CH-CH22- - COOHCOOH stearic stearic acidacid

hydrocarbon chainhydrocarbon chain carboxylcarboxyl (nonpolar “tail”) (nonpolar “tail”) (polar”head”) (polar”head”)

Physical properties:Physical properties:• FA have an FA have an amphipaticamphipatic nature (polar and nonpolar) and in biphasic nature (polar and nonpolar) and in biphasic

systems they orient with the polar end associated with water and systems they orient with the polar end associated with water and the nonpolar end associated with the hydrophobic phase the nonpolar end associated with the hydrophobic phase (detergent–like)(detergent–like)

• The melting point is related to The melting point is related to – chain length: the longer the chain - the higher the melting point, chain length: the longer the chain - the higher the melting point, – number of double bonds: the greater the number of doublebonds – the number of double bonds: the greater the number of doublebonds – the

lower the melting pointlower the melting pointClassified in:Classified in:- SaturatedSaturated- UnsaturatedUnsaturated

SaturatedSaturated FA = zig-zag hydrocarbon chains with even number of FA = zig-zag hydrocarbon chains with even number of C (12-18);C (12-18);

palmiticpalmitic 1616 hexadecanoichexadecanoic CHCH33-(CH-(CH22))1414-COOH-COOH

stearicstearic 1818 octadecanoicoctadecanoic CHCH33-(CH-(CH22))1616-COOH-COOH

lignocerilignocericc

2424 tetracosanoictetracosanoic CHCH33-(CH-(CH22))2222-COOH-COOH

cerebroncerebronicic

2424 -hydroxylignoceric-hydroxylignoceric CHCH33-(CH-(CH22))2121-CH(OH)-COOH-CH(OH)-COOH

Chains with odd number of C exist occasionally, in small amounts in Chains with odd number of C exist occasionally, in small amounts in animal tissues.animal tissues.

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

COOH

Unsaturated FAUnsaturated FA (monoenic, dienic, trienic, tetraenic,…polyenic);(monoenic, dienic, trienic, tetraenic,…polyenic);

Short-chain polyunsaturated fatty acids (Short-chain polyunsaturated fatty acids (SC-PUFASC-PUFA) LA and ALA can not be ) LA and ALA can not be synthesized by humans as they lack the enzymes required for their synthesized by humans as they lack the enzymes required for their production.production.

They form the starting point for the production of long-chain FA (They form the starting point for the production of long-chain FA (LC-PUFALC-PUFA))– Gamma-linolenic acid = GLA (18:3) – Dihomo-gamma linolenic acid = DGLA (20:3)– Arachidonic acid = AA (20:4) – Eicosapentaenoic = EPA (20:5)– Docosahexaenoic = DHA (22:6)

palmitoleic palmitoleic acidacid

16:116:1 ΔΔ99 CHCH33-(CH-(CH22))55--CH=CHCH=CH-(CH-(CH22))77-COOH-COOH

oleic acidoleic acid 18:118:1 ΔΔ99 CHCH33-(CH-(CH22))77--CH=CHCH=CH-(CH-(CH22))77-COOH-COOHlinoleic linoleic acid (LA)acid (LA)

18:218:2 ΔΔ9,129,12 CHCH33-(CH-(CH22))44--CH=CHCH=CH-CH-CH22--CH=CHCH=CH-(CH-(CH22))77-COOH -COOH

α-α-linolenic linolenic acid (ALA)acid (ALA)

18:318:3 ΔΔ9,12,159,12,15 CHCH33-CH-CH22--CH=CHCH=CH-CH-CH22--CH=CHCH=CH-CH-CH22--CH=CHCH=CH-(CH-(CH22))77-COOH-COOH

arachidonic arachidonic acid (AA)acid (AA)

20:420:4 ΔΔ5,8,11,145,8,11,14 CHCH33-(CH-(CH22))44--CH=CHCH=CH-CH-CH22--CH=CHCH=CH-CH-CH22--CH=CHCH=CH-CH-CH22--CH=CHCH=CH--(CH(CH22))33-COOH-COOH

– FA nomenclature:FA nomenclature:• ΔΔ system: palmitoleic acid: 16:1: system: palmitoleic acid: 16:1: ΔΔ99

• systematic name:systematic name:– palmitoleic acid palmitoleic acid = cis-= cis-ΔΔ99-hexadecenoic acid-hexadecenoic acid– oleic acidoleic acid = cis-= cis-ΔΔ99-octadecenoic acid -octadecenoic acid – linoleic acid linoleic acid = cis-= cis-ΔΔ9 9 ΔΔ 12 12-octadecadienoic acid-octadecadienoic acid – linolenic acid linolenic acid = cis-= cis-ΔΔ9 9 ΔΔ 12 12 ΔΔ 15 15 -octadecatrienoic acid-octadecatrienoic acid – arachidonic acidarachidonic acid = cis-= cis-ΔΔ55 ΔΔ8 8 ΔΔ 11 11 ΔΔ 14 14-eicosatetraenoic-eicosatetraenoic

– FA are classified in 4 families depending on the number of C from the FA are classified in 4 families depending on the number of C from the terminal CHterminal CH33 up to the first double bond : up to the first double bond :• ωω-3-3 linolenic acid (ALA)linolenic acid (ALA) CCHH33- - CCHH2 2 --CCH=CH-RH=CH-R

eicosapentaenoic (EPA)docosahexaenoic (DHA)

• ωω-6-6 linoleic acid (LA)linoleic acid (LA) CCHH33-(-(CCHH22))44--CCH=CH-RH=CH-Rgamma-linolenic acid (GLA) dihomo-gamma linolenic acid (DGLA)arachidonic acid (AA)

• ωω-7-7 palmitoleic acid palmitoleic acid CCHH33-(-(CCHH22))55--CCH=CH-RH=CH-R• ωω-9-9 oleic acid oleic acid CCHH33-(-(CCHH22))77--CCH=CH-RH=CH-R

FA with a double bond beyond C9 are not synthesized in the human body, FA with a double bond beyond C9 are not synthesized in the human body, are “essential FA” or “vitamins F”: linoleic, linolenic, arachidonic acidsare “essential FA” or “vitamins F”: linoleic, linolenic, arachidonic acids

ωω-9-9 are not essential in humans, because humans generally possess all the enzymes required for their synthesis

PROSTAGLANDINS (PG)PROSTAGLANDINS (PG)• Hormone-like compounds: Hormone-like compounds:

– synthesized at need, in small amounts, starting from synthesized at need, in small amounts, starting from arachidonic acid, arachidonic acid,

– with short life, with short life, – exert a local action at the site of formationexert a local action at the site of formation

• Location: Location: – first isolated from prostate; first isolated from prostate; – they can occur in all cells and organs except erythrocytesthey can occur in all cells and organs except erythrocytes

• Structure: derived from CStructure: derived from C2020-polyene FA, containing a -polyene FA, containing a cyclopentane ring; cyclopentane ring; – depending on the type and number of oxygen substituents depending on the type and number of oxygen substituents

and location of double bonds in the cyclopentane ring they and location of double bonds in the cyclopentane ring they have several types: A, B, C, D, E, F, G, H; have several types: A, B, C, D, E, F, G, H;

– depending on the number of double bonds in the side chains, depending on the number of double bonds in the side chains, they are: PGEthey are: PGE11, PGE, PGE22, PGE, PGE33 or PGF or PGF11, PGF, PGF2, 2, etcetc

• Prostaglandins actionProstaglandins action• In the In the endocrine glandsendocrine glands : :

– adrenal glands – stimulate the formation of steroid hormones and secretion adrenal glands – stimulate the formation of steroid hormones and secretion of catecholaminesof catecholamines

– thyroid gland – synthesis of iodothyroninesthyroid gland – synthesis of iodothyronines– pancreas – the release of insulinpancreas – the release of insulin

• Control of Control of smooth musclessmooth muscles of bronchi, intestine, uterus (cGMP, Ca of bronchi, intestine, uterus (cGMP, Ca2+2+))– Bronchi muscles contracted by PGDBronchi muscles contracted by PGD22, PGG, PGG22, PGH, PGH22 and relaxed by PGE and relaxed by PGE– Blood vessels muscles are contracted by PGFBlood vessels muscles are contracted by PGF22 and relaxed by PGE and relaxed by PGE2 2

(influence the blood pressure)(influence the blood pressure)– PGEPGE22 increases the volume of urinary discharge and Na increases the volume of urinary discharge and Na++ concentration in concentration in

urineurine– PGFPGF22 stimulates the contraction of uterus and fallopian tubes, increases the stimulates the contraction of uterus and fallopian tubes, increases the

involution of corpus luteum, facilitating the birth involution of corpus luteum, facilitating the birth – PG intensify the intestinal motilityPG intensify the intestinal motility

• The The gastric juice secretiongastric juice secretion is inhibited by PGE and stimulated by PGF is inhibited by PGE and stimulated by PGF22The disturbance of production may determine inflammation, thrombosis, The disturbance of production may determine inflammation, thrombosis,

gastric ulcer or may prevent the ulcer of intestinal or gastric mucosae.gastric ulcer or may prevent the ulcer of intestinal or gastric mucosae.PGFPGF22 (dinoprost) is used in obstetric practice for pregnancy termination (dinoprost) is used in obstetric practice for pregnancy terminationPGEPGE22 (dinoprostone) is used to stop the bronchi spasm, treat hypertension (dinoprostone) is used to stop the bronchi spasm, treat hypertension

or peptic ulceror peptic ulcer

THROMBOXANES (TX)THROMBOXANES (TX)• Structure:Structure:

– analogs of prostanoic acid with a six-membered ring analogs of prostanoic acid with a six-membered ring containing oxygen, containing oxygen,

– the different capital letters designate the combinations the different capital letters designate the combinations of the ring substituents, of the ring substituents,

– the number shows the number of unsaturated bondsthe number shows the number of unsaturated bonds• Functions: Functions:

– TXATXA22 is produced by platelets causing contraction of the is produced by platelets causing contraction of the arteries and triggering the arteries and triggering the platelet aggregationplatelet aggregation, an , an opposite action to PGIopposite action to PGI22 (prostacyclin) produced by the (prostacyclin) produced by the endothelial cells of the vascular system (balanced endothelial cells of the vascular system (balanced working)working)

HYDROPEROXYEICOSATETRAENOIC ACIDS HYDROPEROXYEICOSATETRAENOIC ACIDS (HPETEs)(HPETEs)• Hydroxy-FA derivatives of arachidonic acid, with no ring structureHydroxy-FA derivatives of arachidonic acid, with no ring structure• Function – they can be converted in active compounds such as Function – they can be converted in active compounds such as

leukotrienes.leukotrienes.

LEUKOTRIENES (LT)LEUKOTRIENES (LT)• Formed from HPETEs by lipooxygenase, Formed from HPETEs by lipooxygenase, • Structure:Structure:

– have 3 conjugated double bonds (those formed from have 3 conjugated double bonds (those formed from arachidonic acid have 4), arachidonic acid have 4),

– an additional letter shows the modification to the carbon chain an additional letter shows the modification to the carbon chain (LTA(LTA44, LTB, LTB44)), , • Functions: involved in chemotaxis, inflammation, allergic Functions: involved in chemotaxis, inflammation, allergic

reactionsreactions– LTDLTD44 = the slow-reacting substance of anaphylaxis (SRS-A) = the slow-reacting substance of anaphylaxis (SRS-A)

which causes the contraction of smooth muscle of bronchi, which causes the contraction of smooth muscle of bronchi, blood vessels, coronary arteriesblood vessels, coronary arteries

– LTBLTB44 attracts the neutrophils and eosinophils at the site of attracts the neutrophils and eosinophils at the site of inflammationinflammation

2. ALCOHOLS2. ALCOHOLS• Aliphatic alcohols without nitrogenAliphatic alcohols without nitrogen

– GlycerolGlycerol CHCH2 2 - OH- OH ll CH - OHCH - OH ll CHCH22 - OH - OH

– Higher aliphatic alcohols: stearylic alcoholHigher aliphatic alcohols: stearylic alcohol CHCH33-(CH-(CH22))1616-CH-CH22- OH- OH• Aliphatic alcohols with nitrogenAliphatic alcohols with nitrogen (aminoalcohols) (aminoalcohols)

– Ethanolamine = colamineEthanolamine = colamine HO- CHHO- CH22-CH-CH22-NH-NH22– CholineCholine HO- CHHO- CH22-CH-CH22-N-N++(CH(CH33))33– SerineSerine HO- CHHO- CH22-CH(COOH)-NH-CH(COOH)-NH22– Sphingosine Sphingosine DihydrosphingosineDihydrosphingosine

• Cyclic alcoholsCyclic alcohols: : – InositolInositol

– SterolsSterols• SteroidsSteroids = compounds containing a hydrocarbon skeletal framework as that of gonane = compounds containing a hydrocarbon skeletal framework as that of gonane

(sterane); those which contain a hydroxyl group and can form esters are named (sterane); those which contain a hydroxyl group and can form esters are named sterolssterols• Origin: Origin:

– animal – zoosterols; e.g. cholesterolanimal – zoosterols; e.g. cholesterol– plant – fitosterols; e.g. plant – fitosterols; e.g. ββ-sitosterol-sitosterol

CH3 - (CH2)12 - CH = CH - CH - OH

CH - NH2

CH2 - OH

CH3 - (CH2)12 -CH2 -CH2 - CH - OH

CH - NH2

CH2 - OH

H

OH HH

OHH

OH

OHOH

H HOH

CHOLESTEROLCHOLESTEROL

• Exists in mammalian tissues free or esterified.Exists in mammalian tissues free or esterified.• Location:Location:

– nervous tissue (only free), nervous tissue (only free), – adrenal glands (>80% esterified), adrenal glands (>80% esterified), – liver, liver, – serum (70-80% esterified)serum (70-80% esterified)

• Structural lipid – part of cell membrane (more than Structural lipid – part of cell membrane (more than the membranes of mitochondria, microsomes, the membranes of mitochondria, microsomes, nuclei), influencing the membrane fluiditynuclei), influencing the membrane fluidity

HO

A B

C D1

2

3

45

6

7

8

910

1112 13

17

14 15

16

• Cholesterol functionsCholesterol functions: : – In the liver: In the liver:

• oxidation of the side chain results in oxidation of the side chain results in bile acidsbile acids (cholic and deoxycholic acids = primary bile (cholic and deoxycholic acids = primary bile acids); acids);

• they are they are conjugatedconjugated with glycine or taurine with glycine or taurine forming glycocholic acid or taurocholic acid forming glycocholic acid or taurocholic acid

• eliminated in the bile as eliminated in the bile as bile saltsbile salts (sodium or (sodium or potassium glycocholate or taurocholate). potassium glycocholate or taurocholate).

• chenodeoxycholic and lithocholic are secondary chenodeoxycholic and lithocholic are secondary bile acids formed in the intestine (bacterial bile acids formed in the intestine (bacterial enzymes)enzymes)

• The bile salts are amphypatic molecules with The bile salts are amphypatic molecules with surface-active properties, favoring the surface-active properties, favoring the emulsification of lipids in the intestine; they emulsification of lipids in the intestine; they assist the absorption of fat-soluble vitamins. The assist the absorption of fat-soluble vitamins. The low solubility may favor the formation of gall low solubility may favor the formation of gall stones.stones.

– Synthesis of Synthesis of steroid hormonessteroid hormones in in • adrenal glands (adrenal glands (glucocorticoid, glucocorticoid,

mineralcorticoid)mineralcorticoid) • testis (testis (testosteronetestosterone), ), • ovary (ovary (estradiol, progesteroneestradiol, progesterone), ), • placenta (placenta (progesteroneprogesterone).).

– Steroid vitamins (Steroid vitamins (vitamins Dvitamins D))

COOH

COOH

HO

COOH

HO

OH

COOH

HO

OH

OH

Cholic acid

Deoxycholic acid

Chenodeoxycholic acid

Lithocholic acid

COOH

HO

OH

OH HO

OH

OHHO

OH

OHHO

OH

OH

CO-NH-CH2-CH2-SO3H

HO

OH

OH

CO-NH-CH2-COOH

HO

OH

OH

CO-NH-CH2-COO-Na+

HO

OH

OH

HO

OH

OHHO

OH

OHHO

OH

OH

CO-NH-CH2-CH2-SO3-Na+

HO

OH

OH

cholic acid taurocholic acid

glycocholic acid

sodium taurocholate

sodium glycocholate

BILE ACID CONJUGATED BILE ACID BILE SALTS

CLASSIFICATION OF LIPIDSCLASSIFICATION OF LIPIDS 1. 1. GLYCERIDESGLYCERIDES or ACYLGLYCERIDES or ACYLGLYCERIDES

I.I.HOMOLIPIDSHOMOLIPIDS (esters of fatty acids with tribasic alcohol: glycerol) (esters of fatty acids with tribasic alcohol: glycerol) (SIMPLE LIPIDS) 2. (SIMPLE LIPIDS) 2. STERIDSSTERIDS - esters composed of (esters of fatty acids with sterols)- esters composed of (esters of fatty acids with sterols) lipid monomers 3. lipid monomers 3. WAXESWAXES - fatty acids + alcohols (esters of fatty acids with higher monobasic alcohols)- fatty acids + alcohols (esters of fatty acids with higher monobasic alcohols) - ester bonds - ester bonds LECYTINES LECYTINES

LIPIDSLIPIDS CEPHALINES CEPHALINES with Nwith N SERINCEPHALINES SERINCEPHALINES PLASMALOGENSPLASMALOGENS

1. 1. GLYCEROPHOSPHOLIPIDSGLYCEROPHOSPHOLIPIDS PHOSPHATIDIC ACIDSPHOSPHATIDIC ACIDS (PHOSPHOLIPIDS) (PHOSPHOLIPIDS) without Nwithout N PHOSPHATIDYL- PHOSPHATIDYL-INOSITOLINOSITOL

- all contain P - all contain P CARDIOLIPINS CARDIOLIPINS - alcohol: glycerol- alcohol: glycerol - ester bonds- ester bonds II.II.HETEROLIPIDSHETEROLIPIDS (COMPLEX LIPIDS) (COMPLEX LIPIDS) with Pwith P SPHINGOMYELINS SPHINGOMYELINS - ester or amide bonds - ester or amide bonds CERAMIDESCERAMIDES 2. 2. SPHINGOLIPIDSSPHINGOLIPIDS without Pwithout P CEREBROSIDES CEREBROSIDES - all contain N SULPHOLIPIDS- all contain N SULPHOLIPIDS - alcohol: sphingosine GANGLIOSIDES- alcohol: sphingosine GANGLIOSIDES - amide bonds - amide bonds

I. I. SIMPLE LIPIDSSIMPLE LIPIDS 1. 1. ACYLGLYCERIDESACYLGLYCERIDES

• Esters of glycerol with fatty acids Esters of glycerol with fatty acids • Neutral lipidsNeutral lipids• Classified in mono-, di-, tri-glycerides containing 1, 2, 3 acyl (R-Classified in mono-, di-, tri-glycerides containing 1, 2, 3 acyl (R-

CO-):CO-):– simple acylglycerides: residues of the same FA (Rsimple acylglycerides: residues of the same FA (R11=R=R22=R=R33))– complex acylglycerides: residues from different FAcomplex acylglycerides: residues from different FA

CHCH22 – OH HO-CO-R – OH HO-CO-R11 CHCH22 – O – CO - R – O – CO - R11ll l lCH – OH + HO-CO-RCH – OH + HO-CO-R22 CH – O – CO - RCH – O – CO - R22l l -3H -3H22O lO lCHCH22 – OH – OH HO-CO-R HO-CO-R33 CHCH2 2 - O – CO - R- O – CO - R33

glycerolglycerol fatty acids fatty acids triglyceride (TG) triglyceride (TG)

• Natural neutral lipids are almost exclusively triglycerides (TG); Natural neutral lipids are almost exclusively triglycerides (TG); mono- and di-acylglycerides are formed in the intestine during mono- and di-acylglycerides are formed in the intestine during the digestion and absorption.the digestion and absorption.

monoacylglyceride diacylglyceride triacylglyceridesmonoacylglyceride diacylglyceride triacylglycerides

• Natural fats are mixtures of simple and complex TG, with the Natural fats are mixtures of simple and complex TG, with the prevalence of unsaturated TG. prevalence of unsaturated TG.

• In the human body they contain: In the human body they contain: – oleic acid oleic acid 45%, 45%, – palmitic acid palmitic acid 25%, 25%, – linoleic acid linoleic acid 8%, 8%, – palmitoleic acid palmitoleic acid 7%, 7%, – stearic acid stearic acid 6%6%

CH - OH

CH2 - O - CO - R1

CH2 - OH

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - OH

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - CO - R3

• Physico-chemical propertiesPhysico-chemical properties::– The The melting pointmelting point increases with proportion of saturated fatty increases with proportion of saturated fatty

acidsacids– Less Less densedense than water than water– SolubleSoluble in nonpolar solvents; only mono and diglycerides are in nonpolar solvents; only mono and diglycerides are

water soluble (contain free -OH) forming micelles in water; TG water soluble (contain free -OH) forming micelles in water; TG do not.do not.

– Basic hydrolysisBasic hydrolysis (saponification) (saponification) → glycerol + free fatty acids salts→ glycerol + free fatty acids salts

– In the organism, the hydrolysis is catalyzed by In the organism, the hydrolysis is catalyzed by lipaselipase

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - CO - R3

CH - OH

CH2 - OH

CH2 - OH

+ R2-COOK

R3-COOK

R1-COOK+ 3KOH

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - CO - R3

CH - OH

CH2 - OH

CH2 - OH

+ R2-COOH

R3-COOH

R1-COOH+ 3 H2O

I. I. SIMPLE LIPIDSSIMPLE LIPIDS2. 2. STERIDSSTERIDS

• Esters of cholesterol with fatty acidEsters of cholesterol with fatty acid• Exist in products of animal origin (butter, egg yolk)Exist in products of animal origin (butter, egg yolk)• In the human tissue cholesterides = 75% of total In the human tissue cholesterides = 75% of total

cholesterolcholesterol• In the blood enter in the structure of lipoproteinsIn the blood enter in the structure of lipoproteins

R-OC-O

I. I. SIMPLE LIPIDSSIMPLE LIPIDS3. 3. WAXESWAXES

• Mixtures of ethers and esters of higher monobasic Mixtures of ethers and esters of higher monobasic alcohols and higher fatty acids, usuallyalcohols and higher fatty acids, usually – cetylic alcohol cetylic alcohol CH CH33-(CH-(CH22))1414-CH-CH22-OH-OH– stearylic alcoholstearylic alcohol CHCH33-(CH-(CH22))1818-CH-CH22-OH-OH

palmitic acidpalmitic acid cetylic alcohol cetylic palmitate cetylic alcohol cetylic palmitateThey are products of the animal or plant epidermis, They are products of the animal or plant epidermis, serve as protective film against water loss or wetting serve as protective film against water loss or wetting (high hydrophobic): e.g. leaves and fruits, skin and hair, (high hydrophobic): e.g. leaves and fruits, skin and hair, feathers, skeleton of insects, honey wax.feathers, skeleton of insects, honey wax.

• Energy reserve material (marine animals)Energy reserve material (marine animals)

CH3-(CH2)14-COOH + CH3-(CH2)14-CH2-OH- H2O

CH3-(CH2)14-CO-O-CH2-(CH2)14-CH3

II. II. COMPLEX LIPIDS (HETEROLIPIDS)COMPLEX LIPIDS (HETEROLIPIDS)1. 1. PHOSPHOLIPIDSPHOSPHOLIPIDS

• Complex lipids representative of phosphate-Complex lipids representative of phosphate-substituted esters of diverse organic alcohols.substituted esters of diverse organic alcohols.

• Are polar lipidsAre polar lipids• Predominantly contained in the membranes, Predominantly contained in the membranes,

structural components of organs, mainly in brain and structural components of organs, mainly in brain and nervesnerves

• Take part in metabolic processes: involved in Take part in metabolic processes: involved in intestinal fat resorption, fatty acid transport and intestinal fat resorption, fatty acid transport and oxidation, fatty infiltration of the liver, blood oxidation, fatty infiltration of the liver, blood coagulation, prostaglandin synthesiscoagulation, prostaglandin synthesis

• Classified in:Classified in:– phosphoacylglyceridesphosphoacylglycerides– sphingolipidssphingolipids

II. COMPLEX LIPIDS (HETEROLIPIDS)II. COMPLEX LIPIDS (HETEROLIPIDS)1. PHOSPHOLIPIDS 1. PHOSPHOLIPIDS (PHOSPHOACYLGLYCERIDES)(PHOSPHOACYLGLYCERIDES)

• Structure: Structure: The alcohol = glycerolThe alcohol = glycerol– the –OH in Cthe –OH in C11 is esterified with a is esterified with a saturated FAsaturated FA nonpolar nonpolar– the –OH in Cthe –OH in C22 is esterified with an is esterified with an unsaturated FA (trans)unsaturated FA (trans) hydrophobic hydrophobic– the –OH in Cthe –OH in C33 forms an phosphoester bond with a forms an phosphoester bond with a HH33POPO44 polarpolar– X is an X is an alcoholalcohol residue hydrophylic residue hydrophylic

= = amphipatic characteramphipatic character which makes them easily soluble in nonpolar solvents and in water forming which makes them easily soluble in nonpolar solvents and in water forming

micelles (the hydrophobic radicals oriented to the inner hydrophobic zone; micelles (the hydrophobic radicals oriented to the inner hydrophobic zone; the hydrophylic groups are located on the outer surface toward the aqueous the hydrophylic groups are located on the outer surface toward the aqueous phase)phase)

• They bear both negatively and positively charged groups = They bear both negatively and positively charged groups = amphotericamphoteric charactercharacter

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - P - X

OH O

nonpolar, hydrophobic

polar, hydrophylic

amphipatic structure

1. PHOSPHOLIPIDS (1. PHOSPHOLIPIDS (PHOSPHOACYLGLYCERIDES)PHOSPHOACYLGLYCERIDES)1.1. With N1.1. With N

1.1.1. 1.1.1. LecithinsLecithins (phosphatidylcholines) (phosphatidylcholines)– Structure: FA = oleic, palmitic, stearic acids, (in brain poliunsaturated, > 20 C)Structure: FA = oleic, palmitic, stearic acids, (in brain poliunsaturated, > 20 C)

X = X = cholinecholine HO-CH HO-CH22-CH-CH22-N-N++(CH(CH33))33

the –OH is ionized and associated with Kthe –OH is ionized and associated with K++, Na, Na++, Ca, Ca2+2+

– Location: membranes (50% of lipids in membrane)Location: membranes (50% of lipids in membrane)1.1.2. 1.1.2. CephalinsCephalins (phosphatidyletanolamines) (phosphatidyletanolamines)

– Structure: FA = oleic, stearic Structure: FA = oleic, stearic X = ethanolamine=X = ethanolamine=cholamine cholamine HO-CH HO-CH22-CH-CH22-NH-NH22

– Location: intracellular membranes of animal cells (20%) in all tissues, blood Location: intracellular membranes of animal cells (20%) in all tissues, blood lipoproteins; in plants, microorganismslipoproteins; in plants, microorganisms

1.1.3. 1.1.3. SerincephalinsSerincephalins (phosphatidylserines) (phosphatidylserines)– Structure: X = Structure: X = serineserine HO-CH HO-CH22-CH-NH-CH-NH22

– Location: most animal tissue (brain) Location: most animal tissue (brain) ││1.1.4. 1.1.4. Plasmalogens Plasmalogens COOHCOOH

– Structure: the –OH in CStructure: the –OH in C1 1 forms an ether bond with an forms an ether bond with an acetal acetal HO-CH=CH-CH HO-CH=CH-CH22-R-R11

X = X = colamine colamine HO-CH HO-CH22-CH-CH22-NH-NH22

– Location: all tissues, mainly in brain and spinal cord (50-90%)Location: all tissues, mainly in brain and spinal cord (50-90%)

1. PHOSPHOLIPIDS (1. PHOSPHOLIPIDS (PHOSPHOACYLGLYCERIDES)PHOSPHOACYLGLYCERIDES)1.2. Without N1.2. Without N 1.2.1. 1.2.1. Phosphatidic acidsPhosphatidic acids

– Structure: Structure: X = OHX = OH– Location Location small amounts in animal tissues, intermediary metabolitesmall amounts in animal tissues, intermediary metabolite

1.2.2. 1.2.2. Phosphatidyl inositolPhosphatidyl inositol– Structure: X = inositol (with 1-2 –OH groups esterified with HStructure: X = inositol (with 1-2 –OH groups esterified with H33POPO44))– Location: brain, liver, heart; important in myelin sheets with a high Location: brain, liver, heart; important in myelin sheets with a high

turnover rate; they are bound with proteinsturnover rate; they are bound with proteins1.2.3. 1.2.3. Cardiolipins Cardiolipins

– Structure: Structure: • FA = oleic acid and linoleic acid (1:5)FA = oleic acid and linoleic acid (1:5)• X = phosphatidylglycerolX = phosphatidylglycerol

– Location: heart, animal tissues, mainly in the mitochondria membranesLocation: heart, animal tissues, mainly in the mitochondria membranes

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - P - O - CH2-CH2-N(CH3)3

OH O

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - P - O- CH2-CH2-NH2

OH O

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - P - O - CH2-CH-NH2

OH O COOH

CH - O - CO - R2

CH2 - O - CH = CH - (CH2)13 - CH3

CH2 - O - P - O- CH2-CH2-NH2

OH O

Serincefalines(Phosphatidylserine)

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - P - O

OH O

CH3

CH2 - O - P - O - CH2

CH - O - CO - R3

CH2 - O - CO - R4

OHCH - OH

O

Lecitines(Phosphatidyl-choline)

Cefalines(Phosphatidyl-ethanolamine)

Plasmalogens

Phosphatidic acid

Phosphatidylinositol

Cardiolipins

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - P - OH

OH O

CH - O - CO - R2

CH2 - O - CO - R1

CH2 - O - P - O

OH O

H

OH HH

OHH

OH

OHOH

H H

2. 2. SPHINGOLIPIDSSPHINGOLIPIDS • Structure:Structure:

– alcohol = sphingosinealcohol = sphingosine– R = FA with 24 C (lignoceric, cerebronic, nervonic, R = FA with 24 C (lignoceric, cerebronic, nervonic,

hydroxynervonic)hydroxynervonic)– amide bond between the NHamide bond between the NH22 group of sphingosine and the FA group of sphingosine and the FA

• Classification:Classification:

2.1. With P2.1. With P – – SphingomyelinsSphingomyelins – Structure: X = phosphorylcholine or phosphorylcolamineStructure: X = phosphorylcholine or phosphorylcolamine– Location: nerve tissue white matter (myelin sheath), lungs, Location: nerve tissue white matter (myelin sheath), lungs,

liver, kidney, spleen, blood (erythrocyte membrane)liver, kidney, spleen, blood (erythrocyte membrane)

CH3 - (CH2)12 - CH = CH - CH - OH

CH - NH - CO - R

CH2 - X

CH3 - (CH2)12 - CH = CH - CH - OH

CH - NH - CO - R

CH2 - O - P - O-CH2-CH2-NH2

OHO

CH3 - (CH2)12 - CH = CH - CH - OH

CH - NH - CO- R

CH2 - O - P - O-CH2-CH2-NH3

OO

2. 2. SPHINGOLIPIDSSPHINGOLIPIDS2.2.Without P2.2.Without P

2.1.1. 2.1.1. CeramidesCeramides– Structure: X = OHStructure: X = OH

GlycosphingolipidsGlycosphingolipids contain carbohydrate moieties; they exist in animal tissues contain carbohydrate moieties; they exist in animal tissues in large amount, especially in neurons (normal electric activity and in large amount, especially in neurons (normal electric activity and transmission of nervous impulse):transmission of nervous impulse):

2.1.2. 2.1.2. CerebrosidesCerebrosides – Structure: X = Structure: X = ββ-galactose (or rarely -galactose (or rarely ββ-glucose) -glucose) – Location: brainLocation: brain

2.1.3. 2.1.3. SulfatidesSulfatides (sulfolipids) (sulfolipids)– Structure: X = Galactose-2-sulfateStructure: X = Galactose-2-sulfate– Acidic properties, easily binding cations (transport across the membranes), Acidic properties, easily binding cations (transport across the membranes),

necessary for the normal electric activity of the neuronsnecessary for the normal electric activity of the neurons– Location: white and grey matter of nervous tissue (myelin), liver, kidneys, Location: white and grey matter of nervous tissue (myelin), liver, kidneys,

epidemis, hair, nails (a sulfatide with sialic acid)epidemis, hair, nails (a sulfatide with sialic acid)2.1.4. 2.1.4. GangliosidesGangliosides

– Structure: Structure: • FA = stearic ascid 86-95%, palmitic acid, arachidic acidFA = stearic ascid 86-95%, palmitic acid, arachidic acid• X = olygoglucide composed of monoses and N-acetylneuraminic acid (NANA)= sialic X = olygoglucide composed of monoses and N-acetylneuraminic acid (NANA)= sialic

acidacid– Location : cerebral cortex cells, ganglion cells of CNS, membranes of cells in liver, Location : cerebral cortex cells, ganglion cells of CNS, membranes of cells in liver,

spleen, erythrocytesspleen, erythrocytes

CH3 - (CH2)12 - CH = CH - CH - OH

CH - NH - CO - R

CH2 - OH

CH3 - (CH2)12 - CH = CH - CH - OH

CH - NH - CO - R

CH2 - O

OH O

H H

H

OHH

OH

CH2-OH

H

CH3 - (CH2)12 - CH = CH - CH - OH

CH - NH - CO - R

CH2 - O

OH O

H H

H

O - SO3HH

OH

CH2-OH

H

ceramides

cerebrosides sulfatides

SPHINGOLIPIDOSESSPHINGOLIPIDOSES = inherited genetic disorders (lipid storage diseases) due = inherited genetic disorders (lipid storage diseases) due

to a deficiency of an enzyme that is involved in the to a deficiency of an enzyme that is involved in the normal catabolism of a particular sphingolipid resulting in normal catabolism of a particular sphingolipid resulting in the intracellular accumulation of that lipidthe intracellular accumulation of that lipid

DiseaseDisease Lipid accumulatedLipid accumulated Primary organ Primary organ affectedaffected

• Nyemann-Pick Nyemann-Pick sphingomyelin sphingomyelin brain, liver, spleenbrain, liver, spleen• Gaucher’sGaucher’s glucocerebrosideglucocerebroside brain, liver, spleenbrain, liver, spleen• Krabbes’sKrabbes’s galactocerebrosidegalactocerebroside brainbrain• Metachromatic Metachromatic sulfo-Gal-cerebroside sulfo-Gal-cerebroside brainbrain

leukodystrophyleukodystrophy• Fabry’s Fabry’s ceramide trihexosideceramide trihexoside kidneyskidneys• Tay-SachsTay-Sachs ganglioside GMganglioside GM11 brainbrain

MAIN BIOLOGICAL FUNCTIONS OF LIPIDSMAIN BIOLOGICAL FUNCTIONS OF LIPIDS1.1. EnergeticEnergetic (1g (1g → 9.3 kcal) – FFA, TG, → 9.3 kcal) – FFA, TG, 2.2. StructuralStructural (cell membranes) - C, CE, phosphoglycerides, (cell membranes) - C, CE, phosphoglycerides,

sphingomyelins, sphingomyelins, 3.3. EmulsifyingEmulsifying due to amphipatic character - phosphoglycerides, bile due to amphipatic character - phosphoglycerides, bile

acids acids 4.4. Dissolving of lipid-soluble compoundsDissolving of lipid-soluble compounds (vitamins) in intestine - bile (vitamins) in intestine - bile

acids, sterols acids, sterols 5.5. Transport Transport (cations across the membranes) - phosphoglycerides, (cations across the membranes) - phosphoglycerides,

sphingomyelinssphingomyelins6.6. Electric insulationElectric insulation (myelin sheath) - sphingomyelins (myelin sheath) - sphingomyelins7.7. Mechanical Mechanical (protection of internal organs) - TG(protection of internal organs) - TG8.8. Heat-insulation Heat-insulation (subcutaneous tissue) - TG(subcutaneous tissue) - TG9.9. Hormonal Hormonal - steroid hormones, PG - steroid hormones, PG 10.10. VitaminogenicVitaminogenic - linoleic, linolenic, arachidonic acids - linoleic, linolenic, arachidonic acids

Palmitic acid16Stearic acid18Palmitoleic acid16:Δ9 Oleic acid18: Δ9

Linoleic acid18: Δ9,12

Linolenic acid18: Δ9,12,15

Arachidonic acid20: Δ5,8,11,14

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

COOH

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH

HC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

COOH

H3C

H2C

CH2

H2C

CH2

HC

CH

H2C

CH

HC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

COOH

H3C

H2C

CH

HC

CH2

HC

CH

H2C

CCH

HC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

COOH

H3C

H2C

CH2

H2C

CH2

HC

CH

H2C

CH

HC

CH2

HC

CH

H2C

CH

HC

CH2

H2C

CH2

COOH

H3C

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

H2C

CH2

COOH

H3C

H2C

CH2

H2C

CH2

H2C

CH

HC

CH2

H2C

CH2

H2C

CH2

H2C

CH2

COOH7

9

6

3

6