LIPIDS Introduction

Definition: water insoluble compounds • Most are fatty acids or esters of fatty acids • They are soluble in non-polar solvents such as petroleum ether, benzene, chloroform Lipids

Functions

1. Store energy: fat cells Thermal blanket

2. Chemical messengers: find in nerve fibers and hormones.

3. Parts of membranes: insoluble in water

4. Precursors of hormones (steroids and ) Lipids There are 2 types of lipids; •those that contain the structural component of a ; and

•those that contain the structural component of a four member steroid molecule. Lipids Lipids with fatty acids

1. Simple lipids: Store energy, insulation Triglycerides (Fats & Oils), Waxes

Cell 2. Complex lipids Glycerophospholipids membrane Sphingolipids

3. Eicosanoids Pain, fever, inflammation

Lipids without fatty acids

Chemical messenger Steroids (Cholesterol & steroid hormones) Cell membrane Properties of fats and oils

• fats are solids or semi solids • oils are liquids • melting points and boiling points are not usually sharp (most fats/oils are mixtures) • when shaken with water, oils tend to emulsify • pure fats and oils are colorless and odorless (color and odor is always a result of contaminants) – i.e. butter (bacteria give flavor, carotene gives color) Lipids

Lipids can be categorized as:

1. Hydrolyzable lipids can be converted into small molecules by aqueous hydrolysis. Lipids

Lipids can be categorized as:

2. Nonhydrolyzable lipids cannot be cleaved into smaller molecules by aqueous hydrolysis. Hydrolysis

Most hydrolyzable lipids contain an ester.

Hydrolysis: reaction with water.

(breaking a bond and adding the elements of water)

O O Heat RCOR' + H2O H+ or enzyme RC- OH + H-OR' An ester A carboxylic acid An alcohol Fatty acids

• Fatty acids can be classified either as: ➢saturated (C-C bonds) or unsaturated (also C=C) ➢according to chain length: • short chain FA: 2-4 carbon atoms • medium chain FA: 6 –10 carbon atoms • long chain FA: 12 – 26 carbon atoms ➢ essential fatty acids vs those that can be biosynthesized in the body: – linoleic and linolenic are two examples of essential fatty acid – oleic, stearic – nonessential Fatty acids

• Carboxylic acid are derivatives of long chain

hydrocarbons COOH (18:0) (mp 70°C) – Nomenclature COOH (18;1) (mp 16°C) • Stearate – stearic acid – C18:0 – n-octadecanoic acid COOH (18:2) – General structure of saturated fatty acids: (mp-5°C)

COOHLinolenic acid (18:3) (mp -11°C) Cn H2n+1 COOH n - carbon atoms in a molecule Nomenclature of fatty acids SATURATED FATTY ACIDS

Common name Systematic name Formula C4:0 Butyric Butanoic acid C3H7COOH C6:0 Hexanoic acid C5H11COOH C8:0 Octanoic acid C7H15COOH C10:0 Decanoic acid C9H19COOH C12:0 Dodecanoic acid C11H23COOH C14:0 Tetradecanoic acid C13H27COOH C16:0 Hexadecanoic acid C15H31COOH C18:0 Stearic acid Octadecanoic acid C17H35COOH C20:0 Arachidic Eicosanoic acid C19H39COOH

C24:0 Tetracosanoic acid C23H47COOH

C16:0 Palmitic acid (C15H31COOH)

Structural formula of palmitic acid

CH3 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH2 COOH

CH3(CH2)14COOH

Condensed structural formula of palmitic acid

O C OH

Skeletal formula of palmitic acid Fatty acids

Hydrolyzable lipids are derived from fatty acids.

Fatty acids are: COOH Stearic acid (18:0) (mp 70°C) COOH Oleic acid (18;1) • Long-chain unbranched carbon (mp 16°C) attached to a carboxyl group (-COOH). COOH Linoleic acid (18:2) (mp-5°C) • Typically 12-20 carbon atoms. COOHLinolenic acid (18:3) (mp -11°C) • They have an even number of C atoms. COOH Stearic acid (18:0) (mp 70°C) • Insoluble in water. COOH Oleic acid (18;1) (mp 16°C) Cis COOH Linoleic acid (18:2) (mp-5°C)

COOHLinolenic acid (18:3) (mp -11°C) Fatty acids

CH3(CH2)14COOH (palmitic acid)

polar portion = hydrophillic

nonpolar portion = hydrophobic

Hydrophobic portion is much bigger than hydrophilic portion.

Insoluble in water Saturated and unsaturated Fatty acids

Saturated fatty acids have no double bonds in their long hydrocarbon chains.

Stearic acid: CH3(CH2)16COOH

They are solids at room temperature.

Packed together

COOH COOH COOH COOH COOH Saturated and unsaturated Fatty acids

Unsaturated fatty acids have 1 or more double bonds (generally cis) in their long hydrocarbon chains.

Oleic acid: CH3(CH2)7CH=CH(CH2)7COOH

They are liquids at room temperature. Kinks

They can not pack together

COOH

COOH

COOH COOH COOH Unsaturated fatty acids

• Various conventions are in use for indicating the number and position of the double bond(s)

18 9 1 In chemistry H n (Δ) designation: H3C (CH2)7 C CH(CH2)7COOH 10 Carbon atom numbering starts from Δ = delta COOH group 18:1,9 or 9 18:1

 2 3 4 5 6 7 8 9 10 18

In biochemistry: H3C CH2CH2CH2CH2CH2CH2CH2CH CH(CH2)7COOH ω designation n 17 10 9 1 ω = omega Carbon atom numbering starts from CH3 group 9, C18:1 or n-9, 18:1 Fatty acids

• The human body is capable of synthesizing most fatty acids from carbohydrates or other fatty acids.

• Humans do not synthesize sufficient amounts of fatty acids that have more than one double bond.

• More than one double bond fatty acids are called essential fatty acids and they must be provided by the diet.

Linoleic acid Linolenic acid The Essential Fatty Acids (EFA) are a group of fatty acids that are essential to human health (Omega 6) Fatty acids that contain at least two double bonds, one of them at C6 (carbon atom numbering starts from CH3 group). LINOLEIC ACID 18:2 (9,12) is main representative acid of this group

(CH ) COOH H3C (CH2)4 CH2 2 7 1 8 18 CH CH CH CH 6 7 9 10 (Omega 3) Fatty acids that contain at least two double bonds, one of them at C3 (starting from CH3 group) LINOLENIC ACID 18:3 (9,12,15) is the basic acid of this group

CH (CH ) COOH H3C CH2 2 CH2 2 7 1 2 5 18 CH CH CH CH CH CH 3 4 6 7 Essential Fatty acids

Omega-n acids n: the position of the first double bond

Linoleic acid is called an omega-6 acid, because of the position of the first C=C in the nonpolar chain.

carbon atom numbering starts from CH3 group Essential Fatty acids

Linolenic acid is called an omega-3 acid, because of the position of the first C=C in the nonpolar chain. Omega-3 sources: Omega-6 sources: Flaxeed oil/canola oil Corn oil Fish liver oils/Fish Peanut oil eggs Cottonseed oil Human Milk Soybean oil Seafood/Fatty fish Many plant oils - albacore tuna - mackerel - salmon -sardines

➢Proper n-6 to n-3 ratio in a diet is 4:1 Fatty acids

• C3H7COOH (butanoic acid) – short chain FA • Common medium-chain saturated fatty acids:

C5H11COOH caproic acid (hexanoic acid)

C7H15COOH caprylic acid (octanoic acid)

C9H19COOH capric acid (decanoic acid)

CH2 CH2 COOH 5 3 1 caproic acid H3C CH2 CH2 6 4 2

➢ liquid (C1 to C6), solid (from C7) Fatty acids

• common long-chain saturated FA’s:

C11H23COOH : lauric acid (n-dodecanoic acid; C12:0)

C13H27COOH : myristic acid (n-tetradecanoic acid; C14:0)

C15H31COOH : palmitic acid (n-hexadecanoic acid; C16:0)

C17H35COOH; stearic acid (n-octadecanoic acid; C18:0)

C19H39COOH; arachidic (eicosanoic acid; C20:0)

C23H47COOH; lignoceric acid

C25H51COOH; Less common fatty acids H C 3 R= COOH R • R iso – isobutyric acid H3C H3C

• odd carbon fatty acid – CH3 • hydroxy fatty acids – ricinoleic acid, dihydroxystearic acid, cerebronic acid (found in higher plants) • cyclic fatty acids – hydnocarpic, chaulmoogric acid (nonedible fat and oil isolated from chaulmoogra oil, used in LEPROSY treatment) (CH2)12-CO2H (CH2)10-CO2H

chaulmoogric acid hydnocarpic acid MonoUnsaturated fatty acids MUFA

• Monoenoic acid (monounsaturated) Cn H2n-1 COOH

There is free rotation about C-C bonds in the fatty acid hydrocarbon, except where there is a double bond. Double bond is always cis in natural fatty acids.

CH3 (CH2)6 CH2 CH2 (CH2)6 COOH 18 11 8 1 C C 10 9 H H COOH Oleic acid 18:1 n-9(cis) or 18:1 (Δ9)

Chemical formula • C18H34O2 18:1 (9trans) • C17H33 COOH Unsaturated fatty acids

• Dienoic acid: linoleic acid 18:2 (9cis, 12cis)

CH3 (CH2)4 CH=CH CH2 CH=CH (CH2)7 COOH

Chemical formula

C H O 18 32 2 cis C17H31COOH linoleic acid

Trienoic acid: linolenic acid 18:3 (9cis, 12cis, 15cis) PolyUnsaturated fatty acids PUFAs • Polyenoic acid (polyunsaturated, tetranoic acid)

COOH

CH3

Arachidonic acid 20:4 (Δ 5,8,11,14)

PUFAs are fatty acids that contain more than one double bond in their backbone UNSATURATED FATTY ACIDS

Oleic acid 9 COOH CH3-(CH2)7-CH=CH-(CH2)7-COOH 18:1 ω-9 cis Δ 18 9 CH -(CH ) -CH=CH-(CH ) -COOH Elaidic acid 18 3 2 7 2 7 9 COOH 18:1 ω-9 trans Δ 9 12 9 CH -(CH ) -(CH=CH-CH ) -(CH ) -COOH Linoleic acid (LA) COOH 3 2 4 2 2 2 6 18:2 ω-6 cis Δ 9,12 18 12 9 6 CH -(CH ) -(CH=CH-CH ) -(CH ) -COOH γ-Linolenic acid (GLA) 3 2 4 2 3 2 3 6,9,12 18:3 ω-6 cis Δ 18 COOH CH -CH -(CH=CH-CH ) -(CH ) -COOH α-Linolenic (ALA) 3 2 2 3 2 6 9,12,15 COOH 18:3 ω-3 cis Δ 18 9 14 11 8 5 CH -(CH ) -(CH=CH-CH ) -(CH ) -COOH COOH 3 2 4 2 4 2 2 20:4 ω-6 cis Δ 5,8,11,14 20 17 14 11 8 5 CH -CH -(CH=CH-CH ) -(CH ) -COOH 20 COOH 3 2 2 5 2 2 (EPA) 20:5 ω−3 cis Δ 5,8,11,14,17 19 7 4 CH -CH -(CH=CH-CH ) -CH -COOH 22 16 13 10 3 2 2 6 2 (DHA) COOH 22:6 ω−3 cis Δ 4,7,10,13,16,19

Comparison of melting points

Melting Points of Saturated vs. Unsaturated Fatty Acids: the unsaturated fatty acids have lower melting points than the saturated fatty acids.

The introduction of one or more double The molecular structure allows bonds in the hydrocarbon chain in many fatty acid molecules to be unsaturated fatty acids results in one or rather closely "stacked" together. more "bends" in the molecule. These Close intermolecular interactions molecules do not "stack" very well. The result in relatively high melting intermolecular interactions are much points. weaker than saturated molecules. As a result, the melting points are much lower for unsaturated fatty acids. Comparison of melting points Melting Points of Saturated vs. Unsaturated Fatty Acids: the unsaturated fatty acids have lower melting points than the saturated fatty acids. Comparison of melting points 18:0 18: 1 18:3

Melt.p. 70oC 16oC -11oC

COOH Saturated FA (highest melting point)

COOH Unsaturated trans (intermediate m.p.)

COOH

Unsaturated cis (lowest m.p.) Function of EFAs

• Formation of healthy cell membranes • Proper development and functioning of the brain and nervous system • Production of hormone-like substances called Eicosanoids –Thromboxanes –Leukotrienes –Prostaglandins They are responsible for regulating blood pressure, blood viscosity, immune and inflammatory responses. Waxes

Wax is an ester of saturated fatty acid and long chain alcohol.

Ester bond Long-Longchain-chainalcohol alcohol Fatty acid

Acid Waxes

Because of their long nonpolar C chains, waxes are very hydrophobic.

O Beeswax CH3(CH2)14 C O(CH2)29CH3 (myricyl palmitate) hydrophobic hydrophobic region region

They form protective coatings:

- In plants, they help prevent loss of water and damage from pests.

- In humans and animals, provide waterproof coating on skin and fur. Beeswax Carnauba Coating

Jojoba

Lanolin from wool lotions Waxes

Hydrolysis reaction: like other esters, waxes are hydrolyzed.

Heat Soaps a soap is Hydrophobic part: nonpolar a salt of a fatty acid

Hydrophilic part: polar (remains in contact with environment)

O O CH2 OCR CH2 OH O saponification - + + + RCOCH O 3 NaOH CHOH 3 RCO Na CH2 OCR CH2 OH A triglyceride 1,2,3-Propanetriol Sodium soaps ( a triester of glycerol) (Glycerol; glycerin) Soaps

Organization of soaps molecules in water

Na+ + + Soaps solution + - a micelle (emulsion type o/w) +++ + fat +

+ + + + water O H H Soaps

When soap is mixed with dirt (grease, oil, and …), soap micelles “dissolve” these nonpolar, water-insoluble molecules. Soaps water insoluble water soluble -barium, magnesium, calcium soaps

(C15H31COO)2Ba hard Soaps don’t work effectively -sodium soaps in hard water! e.g. soap bar soft - + -potassium soaps, e.g shampoo, C17H35COO Na shaving soaps, liquid soaps - + C17H35COO K polar hydrophilic carboxylate group COO-

Amphipatic (amphiphilic) nature of a soap

nonpolar hydrophobic hydrocarbon chain

e.g. stearate C17H35- Detergents

➢ Synthesis of detergents

(CH )n-CH (CH )n-CH 2 3 H SO (CH2)n-CH3 2 3 2 4 NaOH

_ n=10-20 OSO H + 2 OSO2 Na alkylbenzene alkylbenzenesulfonic acid sodium salt of alkylbenzenesulfonic acid

These substances are usually alkylbenzenesulfonates Polar sulfonate (of detergents) is less likely than the polar carboxylate (of soap) to bind to calcium and other ions found in hard water. ➢ Detergents work effectively in hard water – their barium or magnesium salts are water soluble Simple lipids

• Glycerides (fats and oils) – Glycerol CH2OH

H C OH

CH2OH glycerol

– Esters of glycerol - monoglycerides, diglycerides and triglycerides

• Waxes – simple esters of long chain alcohols and long chain fatty acids GLYCERIDES O

H2C O C (CH2)14 CH3

HO C* H 1-palmitomonoglyceride

H2C OH

O O H C O C (CH ) 2 2 14 CH3 H2C O C (CH ) CH CH (CH2)7 CH3 O 2 7 HO C H CH3 (CH2)16 C O C* H

H C O C (CH ) 2 2 14 CH3 H2C OH O 1,3-dipalmitodiglyceride 1-oleo-2-stearodiglyceride

O

H2C O C (CH2)14 CH3 O CH3 (CH2)14 C O C H Triglyceride (tripalmitin)

H2C O C (CH2)14 CH3 O Function: storage of energy in compact form and cushioning Triglycerides

1-stearoyl-2,3 linoleoyl glyceride Triglycerides chemical properties ➢ Acidic hydrolysis (reaction reversible) O HO H2C O C R C R1 H C O H 1 O 2 O H+ HO HC O C R 3H O 2 + 2 C R2 + HC O H O HO H2C O C R3 H2C O H C R3 O O Triglyceride fatty acids glycerol

➢ Basic hydrolysis (SAPONIFICATION, reaction irreversible) O ONa H C O C R H C O H 2 1 R1 C 2 O O 3NaOH ONa HC O C R2 + HC O H R2 C + O

H2C O C R3 ONa H2C O H O R3 C O Triglyceride salts of fatty acids glycerol (soaps) Triglycerides chemical properties

➢ Enzymatic hydrolysis (reaction reversible) – a STEREOSELECTIVE reaction

O H C O C 2 R1 H C O H OH 2 O lipase R1 C O O HC O C R2 + 2H2O HC O C + R2 OH R3 C H2C O C R3 O H2C O H O Fatty acids of Triglyceride 2-monoglyceride carbons C1 i C3

After ca. 5 minutes isomerization of a fatty acid group from C2 to C1 position occurs.

Afterwards hydrolysis of the last FA group happens. Triglycerides chemical properties

➢ Hardening (hydrogenation)

CH3 O (CH2)7 O

H2C O C (CH2)7 CH CH H2C O C (CH2)16 CH3 O Ni O CH CH (CH2)7 C O C H + 3H2 CH3 (CH2)16 C O C H CH (CH ) 3 2 7 H C O C (CH ) CH CH 2 2 7 H2C O C (CH2)16 CH3 O O (H2C)7 CH3

Triolein Tristearin (liquid plant fat) (solid fat: margarine)

The fastest hydrogenation occurs at position C-1 and C-3 and for fatty acids rests containing four-three double bonds

Negative side effects: trans fatty acids obtaining, changing of double bond positions, polimerization of double bonds Triglycerides chemical properties

➢Transesterification – to make fats more nutritious and healthy, to introduce omega-3 and omega-6 fatty acids to the structure of edible fats. ➢ No unfavourable side effects during synthesis.

O O O O H C O C H C O C C H H2C O C C15H31 2 C17H35 2 17 35 H2C O C C15H31 O O O NaOH O C H CH O C C H CH O C C17H33 CH O C 17 33 + 17 33 + CH O C C17H33 H C O C H C O C C H H2C O C C15H31 2 C17H29 2 15 31 H2C O C C17H29 O O O O substitute of cocoa butter 1-stearo-2-oleo-3-palmitin ➢It is the source of structured fats. O

H2C O SHORT/MEDIUM CHAIN FATTY ACID O - HC O OMEGA 3 or -6 FATTY ACID

H2C O SHORT/MEDIUM CHAIN FATTY ACID

O Types of Fatty Acid Lipids

phospate phospate

Phospholipids Phospholipids

Phospholipids are lipids that contain a P atom.

Two common types: Phospholipids

1. Phosphoacylglycerols (glycerophospholipids):

They are the main component of most cell membranes.

Structurally, they resemble a triacylglycerol, except the third fatty acid has been replaced with a phosphodiester bonded to an alcohol.

Fatty acid

Fatty acid

Amino alcohol Phospholipids - main components

O H2C OH HO C H HO P OH OH H2C OH

Glycerol Phosphoric acid

➢ Hydroxyl compounds:

COOH HO CH2 CH serine NH2

+ HO CH2 CH2 NH3 ethanolamine

CH3 + HO CH2 CH2 N CH3 choline CH3

OH HO OH HO OH inosytol HO Phospholipids

1. Phosphoacylglycerols:

Ethanolamine Choline Phospholipids

1. Phosphoacylglycerols:

O

H C O C C15H31 O 2

C17H35 C O C* H O

H2C O P O R OH Ester bond

Their names depending on R:

COOH CH2 CH Phosphatidylserine (cephaline) NH2 + Phosphatidylethanolamine (cephaline) CH2 CH2 NH3

CH3 + CH2 CH2 N CH3 Phosphatidylcholine (lecithine) CH3 Phospholipids 1. Phosphoacylglycerols:

O phosphoester bond + H2C O P O CH2 CH2 N(CH3)3 O OH - phosphatidylcholine (-lecithine) C17H35 C O C* H

H C O C C H ester bond 2 15 31 O

O H C O C C H O 2 15 31 -phosphatidylethanolamine + H3N CH2 CH2 O P O C* H (- cephaline) OH O H2C O C C15H31 hydrophilic hydrophobic

Natural phospholipids are L i . Phospholipids 2 Plasmalogens - form 10% of brain and muscles phospholipids

Ether bond

H R1 – rest of an alcohol H C O C CH R1 (mainly unsaturated) O H R C O C* H R – rest of fatty acids O + Ethalomine H C O P O CH CH NH 2 2 2 3 Serine OH ethanolamine Choline Inositol Ethanolamine plasmalogen

They have anticancer properties. Phospholipids

3. Sphingolipids (Sphingomyelins): They differ in two ways: 1. They do not contain a glycerol backbone, they have a sphingosine backbone instead.

sphingosine

2. They do not contain an ester; their single fatty acid is bonded to the backbone by an amide bond. Phospholipids

3. Sphingolipids (Sphingomyelins)

The myelin sheath, the coating that surrounds nerve cells, is rich in sphingomyelins. Phospholipids 3. Sphingolipids (Sphingomyelins) -forms the myeline sheath around the axon of a neuron. It is essential for the proper functioning of the nervous system.

O CH (CH ) H 3 2 12 CH3(CH2)12 H HN C R NH2 C C C CH CH CH OH C H 2 H CH CH CH2 OH OH OH Sphingosine Ceramide

Amide bond

O R – rests of fatty acids H CH3(CH2)12 HN C R O R1 – rests of C C choline, serine, H CH CH CH2 O P O R1 ethanolamine OH OH Ester bond Sphingomieline Phospholipids 3. Sphingolipids (Sphingomyelins)

Sphingomieline Glycolipids

➢ Cerebrosides - is a sphingolipid (ceramide) with a monosaccharide such as glucose or galactose as polar head group. sphingosine Fatty acid, CH (CH ) H HN C (CH )OH (CH ) CH 3 2 12 2 2 21 3 e.g. Cerebronic acid C C O H CH CH OH ➢ gangliosides – a polar head group that is a complex oligosaccharide. CH2 OH O CH2 H C O H Cerebrosides and gangliosides, collectively called C OH H C glycosphingolipids, are commonly found in the HO C C H outer leaflet of the plasma membrane bilayer, with their sugar chains extending out from the cell H OH surface. Sugar, e.g. gluctose Component Structures of Some Important Membrane Lipids Prostaglandins-prostanoids (eicosanoids) A is any member of a group of compounds that are derived enzymatically from fatty acids. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. They are local hormones and have a wide variety of actions: - cause constriction or dilation in vascular smooth muscle cells - cause aggregation or disaggregation of platelets - sensitize spinal neurons to pain - decrease intraocular pressure - regulate inflammatory mediation - regulate calcium movement COOH 1 - control hormone regulation 8

- control cell growth 12 20

Prostanoic acid Prostaglandins-prostanoids (eicosanoids)

Linoleic acid (18:2) acyclic compound

OH 8 5 5 COOH COOH 6 1 1 8 20 11 14 10 20 Arachidonic acid(20:4) 12 14 OH

CYCLOOXYGENASE aspirine inhibits it LTB4 (leukotriene)

O 5 COOH 1 20 O 13 15 OH OH O COOH 6 1 PGH2 O 9 9 5 COOH 1 11 21 20 11 14 16 13 15 HO O OH OH OH OH 9 5 COOH TXB2 (thromboxane) 6-keto-PGF1 1 20 11 (prostacyclin) 13 15 OH OH PGF2 (prostaglandin) Cyclic compounds Eicosanoids

Prostaglandins and Leukotrienes are two types of eicosanoids (20 C atoms derived from the fatty acids).

- All eicosanoids are very potent compounds, which are not stored in cells, but rather synthesized in response to external stimulus.

- Unlike hormones they are local mediators, performing their function in the environment in which they are synthesized. Prostaglandins

Prostaglandins are responsible for inflammation.

- Aspirin and ibuprofen relieve pain and inflammation by blocking the synthesis of these molecules.

- Prostaglandins also decrease gastric secretions, inhibit blood platelet aggregation, stimulate uterine contractions, and relax smooth muscles.

- There are two different cylcooxygenase enzymes responsible for prostaglandin synthesis called COX-1 and COX-2. Prostaglandins

COX-1 is involved in the usual production of prostaglandins.

COX-2 is responsible for additional prostaglandins in inflammatory diseases like arthritis.

- Nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin and ibuprofen inactivate both COX-1 and -2, but increase risk for stomach ulcer formation.

- Drugs sold as Vioxx, Bextra, and Celebrex block only the COX-2 enzyme without affecting gastric secretions. Leukotrienes

Asthma is characterized by chronic inflammation, so inhaled steroids to reduce this inflammation are commonly used.

Leukotrienes are molecules that contribute to the asthmatic response by constricting smooth muscle of the lung.

New asthma drugs act by blocking the synthesis of

leukotriene C4, which treat the disease instead of just the inflammation symptoms. Steroids

Steroids have:

• A steroid nucleus which is 4 carbon rings.

• Attached groups that make the different types of compounds.

(steroid nucleus) • No fatty acids. Steroids ➢ the group of naturally occuing compounds (plants, animals, microorganisms)

All of them possess the 4-ring skeleton of STERAN (1,2-cyclopentano- perhydrofenantrene). R3

R2 12 12 17 17 11 13 11 13 R1 D 16 16 C R , R – mainly C D 1 9 14 1 2 1 9 14 15 15 2 10 8 CH groups 2 10 8 3 A B A B 3 5 7 3 5 7 R3 – hydrocarbon 4 6 4 6 chain of different Steran Common steroids’ skeleton length

Steroids differ in: mutual arrangement of condensed rings– A/B, B/C and C/D,

degree of unsaturation, and type and length of side chains R1, R2 and R3.

➢ sterols –steroids contaning -OH group in the C3 position Cholesterol and cholesterol esters

CH CH2 CH 3 CH2 3 Functions: x CH2 HC CH3 -serves as a component of cell membranes (moderates CH3 17 membrane fluidity) 13x x CH3 -precursor to steroid hormones x -storage and transport – as cholesterol palmitate esters or x x 10 x esters with linolenic acid

3x 5 HO 6 The hydroxyl at C-3 is hydrophilic; the rest of the molecule is hydrophobic (amphipatic molecule); also 8 centers of asymmetry

H3C CH3 H3C CH2CH3 CH3 CH H C 3 3 CH3 H C 3 CH3 CH3 CH3

-Sitosterol HO Ergosterol, in fungi HO (phytosterol, in plants) (to progesteron production) (to vit. D2 production) Cholesterol sources, biosynthesis and degradation

• diet: only found in animal fat • biosynthesis: primarily synthesized in the liver from acetyl-coA; biosynthesis is inhibited by LDL (low density lipoprotein) uptake • degradation: only occurs in the liver Cholesterol

Cholesterol:

• Is the most abundant steroid in the body.

• Insoluble in water (need a water soluble carrier).

• Has methyl CH3- groups, alkyl chain, and -OH attached to the steroid nucleus.

CH 3 CH3 CH3 CH3 CH3

HO Lipoproteins

Water-soluble form of lipids Triacylglycerols (soluble in blood)

Spherical particles

Polar surface and nonpolar inner

Transporting lipids through the bloodstream to tissues where they are stored, Used for energy, or to make hormones. Lipoproteins

VLDL: very-low-density lipoprotein Triglycerides and Cholesterol

LDL: low-density lipoprotein (bad Cholesterol) Cholesterol

HDL: high-density lipoprotein (good Cholesterol) Cholesterol

Recommended levels are: HDL > 40 mg/dL, LDL < 100 mg/dL, total serum cholesterol < 200 mg/dL.

Chylomicrons Triglycerides and Cholesterol

VLDL

Fat storage Heart and Liver cells muscles Intestine Energy and HDL elimination LDL Steroid Hormones

A hormone is a molecule that is synthesized in one part of an organism, which then elicits a response at a different site.

Two types of steroids hormones:

1. Sex hormones Estrogens & progestins in females Androgens in males

2. Adrenal Cortical Steroids Sex Hormones

Estrogens (Female Sex Hormones):

The estrogens estradiol and estrone control development of secondary sex characteristics, regulate the menstrual cycle, and are made in the ovaries. Sex Hormones

Progestins (Female Sex Hormones):

The progestin progesterone is called the “pregnancy hormone”; it is responsible for the preparation of the uterus for implantation of a fertilized egg. Sex Hormones

Androgens (Male Sex Hormones):

Testosterone and Androsterone are androgens made in the testes.

They control the development of secondary sex characteristics in males. Adrenal Cortical Steroids

Aldosterone regulates blood pressure and volume by controlling the concentration of Na+ and K+ in body fluids.

Cortisone and cortisol serve as anti-inflammatory agents, which also regulate carbohydrate metabolism.

aldosterone cortisone

cortisol Vitamins

They are organic compounds required in small quantities for normal metabolism.

They must be obtained from the diet (our cells cannot synthesize them).

Vitamins are either water soluble or fat soluble.

The four fat-soluble vitamins (A, D, E, and K) are lipids and nonpolar.

They are found in fruits, vegetables, fish, liver, and dairy products.

Excess vitamins are stored in adipose cells to be used when needed. Vitamins

Vitamin A

It is found in liver, fish, and dairy products, and is made from β-carotene (the orange pigment in carrots).

It is needed for vision and for healthy mucous membranes.

Vitamin A deficiency causes night blindness and dry eyes and skin. Vitamins

Vitamin D

Vitamin D can be synthesized from cholesterol. It is produced in the skin on exposure to UV radiation It can be obtained in the diet from many foods, especially milk, and helps regulate Ca and P metabolism.

Is necessary for normal bone growth and function. A deficiency of vitamin D causes rickets (bone malformation). Vitamins

Vitamin E

Vitamin E is an antioxidant, protecting unsaturated side chains in fatty acids from unwanted oxidation.

Deficiency of vitamin E causes numerous neurological problems, although it is rare. Vitamins

Vitamin K

Vitamin K regulates the synthesis of clotting proteins (prothrombin), and deficiency of this leads to excessive or fatal bleeding. Schematic Diagram of a Cell Membrane

The phospholipid bilayer with embedded cholesterol and protein molecules. Short oligosaccharide chains are attached to the outer surface. Lipid bilayer

Extracellular matrix Glycoprotein

Carbohydrate

Glycolipid Plasma membrane

Phospholipid Proteins Microfilaments Cholesterol of cytoskeleton Cytoplasm

➢ Main components of lipid bilayer are: phospholipids, glycosphingolipids and cholesterol (all lipids from 20 to 75%), proteins (ca. 50%), carbohydrates ➢ The bilayer has LIQUID-CRYSTAL CHARACTER ➢ In the liquid crystal state, hydrocarbon chains of phospholipids are disordered and in constant motion ➢ At lower temperature, a membrane containing a single phospholipid type undergoes transition to a crystalline state in which fatty acid tails are fully extended, packing is highly ordered Lipid bilayer ➢ Cholesterol inserts into bilayer membranes with its hydroxyl group oriented toward the aqueous phase and its hydrophobic ring system is very close to fatty acid chains of phospholipids ➢ Cholesterol regulates bilayer fluidity - interaction with the relatively rigid cholesterol decreases the mobility of hydrocarbon tails of phospholipids ➢ In the absence of cholesterol, such membranes would crystallize at physiological temperatures Saponification number • the highest mass of a triglyceride, the lowest saponification number • defined as the number of milligrams of KOH needed to neutralize the fatty acids in 1 gram of fat • butter (large proportion of short chain FAs) sap. no. 220 – 230 • oleomargarine (long chain FAs) sap. No is 195 or less O O K H C O H H31C15 C 2 O H2C O C C15H31 O O K HC O H H C C O C H 3 KOH H31C15 C + 31 15 + O

H2C O C C15H31 O K H2C O H H31C15 C O O

806 g tripalmitin - 3 . 56 g KOH 1 g - x x = 0,208 g = 208,4 mg Iodine number • measures the degree of unsaturation in a given amount of fat or oil • the iodine number is the number of grams of iodine absorbed by 100 grams of fat • Cottonseed oil: 103 –111 • Olive oil: 79 – 88 • Linseed oil: 175 –202 • frequently used to determine adulteration of commercial lots of oils (older fats have lower iodine numbers) 854 g glyceride - 4 . 254 g iodine CH3 100 g - x (CH ) O 2 7 x = 119,9 g H2C O C (CH2)7 CH CH CH CH CH CH CH CH O (CH ) C O C H + 4I H3C CH2 CH2 2 7 2 dioksan H2C O C15H31 O I I

I I I I I I H2C O C (CH2)7 CH HC (CH2)7 CH3 CH HC CH CH CH HC O H C (CH ) C O C H 3 CH2 CH2 2 7

H2C O C15H31 Thank You