Prof. Dr. Suat Erdoğan EBN School of Medicine Medical Biochemistry Department October 2013

Prof. Dr. Suat ErdoğanEBN School of Medicine

Medical Biochemistry DepartmentOctober 2013

OutlineDescription of lipidsFunction of lipids Fatty acids Triglycerides Cholesterol Steroids

LipidsLipids (or fats) are a heterogeneous class of naturally occurring organic compounds classified together on the basis of common solubility properties.

They are insoluble in water, but soluble in nonpolar solvents, including ether, chloroform, benzene and acetone.

Major lipids Lipids may be polar or nonpolar

(amphipatic). Polar lipids have limited solubility in water because they are amphipatic.

Major lipids includetriacylglycerols, phosphodiacylglycerols,

sphingolipids, glycolipids, lipid-soluble vitamins, and prostaglandins

cholesterol, steroid hormones, and bile acids

Properties of LipidsDo not readily dissolve in waterFats are solid at room temperatureOils are liquid at room temperatureTriglycerides are the main form of

lipids in food and body (storage)Energy dense (9 kcal/g)

Functions of LipidsProvide energy Efficient storage of energyInsulationProtectionTransport fat-soluble vitaminsMembrane componentsSatietyFlavor and mouth feel

Provide and Provide and storage of energy storage of energy

In the body, fat serves as an efficient source of energy (ATP), both directly and potentially when stored in adipose tissue.

Fat cells in the bodyThe fat is stored in living cells, called fat cells (= adipocyte). Adipocytes makes adipose tissue.

Isolation Fats serves as a thermal

insulator in the subcutaneous tissues and around certain organs, and

Nonpolar lipids act as electrical insulators allowing rapid propagation of depolarization waves along myelinated nerves.

Protection Protection Below the dermis lies a layer of fat that helps insulate the body from heat and cold, provides protective padding, and serves as an energy storage area.

Transport fat-soluble vitaminsCombinations of fat and protein (lipoproteins) are important cellular constituents, occurring both in the cell membrane and in the mitochondria within the cytoplasm, and serving also as the means of transporting lipids in the blood.

Membrane componentsMembrane componentsMembrane lipids are a group of compounds (structurally similar to fats and oils) which form the double-layered surface of all cells. The three major classes of membrane lipids are phospholipids, glycolipids, and cholesterol.

SatietySatietyLipids suppress food intake when present in the small intestine of both humans and animals.

Flavor and mouth feelFlavor and mouth feelFats have little taste, but contribute

mouth feel and carry odorants.

Fat has a major influence on the sensory perception of food products. Fats enhance the taste and acceptability of foods, and lipid components largely determine the texture, flavor and aroma of foods.

LipidsLipids are classified as simple and complex are classified as simple and complex

1. Simple lipids: esters of fatty acids with various alcohols.a.Fats: esters of fatty acids with glycerol. A fat in the liquid state is known as oil.b.Waxes

2. Complex lipids: esters of fatty acids containing groups in addition to an alcohol and fatty acids.PhospholipidsGlycolipidsOther complex lipids

Fatty acidsFatty acids occur mainly as esters in natural fats

and oils but do occur in the unesterified form as free fatty acids (FFA), a transport form found in the plasma.

The fatty acid chain may be saturated (containing no double bonds) or unsaturated (containing one or more double bonds). Unsaturated fatty acids may be further subdivided as follows:

a.Monoansaturated acids, containing one double bond (oleic acid).

b.Polyunsaturated acids containing two or more double bonds (linoleic acid, arachidonic acid).

omega end alpha end

degree of saturation

H H H H H H H H H H H H H H H H H O

H-C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C--C-C-OH

H H H H H H H H H H H H H H H H H

Stearic acid: C18H38O2

Saturated fatty acidsLauric acid (12 C) Myristic acid (14 C) Palmitic acid (16 C) Stearic acid (18 C) Arachidic acid (20 C)

Unsaturated fatty acids Palmitoleic acid (16:1) Oleic acid (18:1) Linoleic acid (18:2) -Linolenic acid (18:3) -Linolenic acid (18:3) Arachidonic acid

(20:4)

16:1 mean: a fatty acid contains 16C and 1 double bond in the structureColored in red demonstrates essential fatty acids.

Deficiency of essential fatty acidsDeficiency of essential fatty acidsEssential fatty acid

deficiency results in dermatitis.

Clinical signs of essential fatty acid deficiency include a dry scaly rash, decreased growth in infants and children, increased susceptibility to infection and poor wound healing.

omega end alpha end

One double bond

H H H H H H H H H H H H H H H O

H-C--C--C--C--C--C--C--C--C=C--C--C--C--C--C--C--C--C-OH

H H H H H H H H H H H H H H H H H

omega end alpha end

> 2 double bonds

H H H H H H H H H H H H H O

H-C--C--C--C--C--C=C--C--C=C--C--C--C--C--C--C--C--C-OH

H H H H H H H H H H H H H H H H H

omega end alpha end

1st double bond is located on the 6th carbon from the omega end

H H H H H H H H H H H H H O

H-C--C--C--C-- C--C =C--C--C=C--C--C--C--C--C--C--C--C-OH

H H H H H H H H H H H H H H H H H

Omega-6 (linoleic) fatty acidFound in vegetable oilsOnly need ~ 1 tablespoon a dayArachidonic acid can be made from

omega-6Metabolized to form eicosanoids

omega end alpha end

1st double bond is located on the 3rd carbon from the omega end

H H H H H H H H H H H H H H H H H O

H-C--C--C=C--C--C =C--C--C=C--C--C--C--C--C--C--C--C-OH

H H H H H H H H H H H

Omega-3 (linolenic) fatty acidPrimarily from fish oilAlso found in canola or soybean oilMetabolized to form eicosanoidsRecommend intake of ~2 servings of fish

per week.

Essential Fatty AcidsMust be eatenBody can only make double bonds

after the 9th carbon from the omega end.

Needed for immune function, vision, cell membrane, and production of hormone-like compounds.

Signs and Symptoms of Essential Fatty Acids Deficiency

Itchy skinDiarrheaInfectionsRetarded growth and wound

healingAnemia

Fats

Triglycerides (=triacylglycerol)Triglycerides are the main storage forms of fatty

acids. Triglycerides are esters of the alcohol glycerol

and fatty acids.

(Ester bond)

Glycerol + 3 FA’s Triglyceride + 3 H20

H

H--C--OH

H--C--OH

H--C--OH

H

O

HO-C-R

O

HO-C-R

O

HO-C-R

+

H O

H--C--O--C--

O

H--C--O--C--

O

H--C--O--C--

H

R + H2O

R + H20

R + H20

esterification/reesterification

desterfication

H

H--C--OH

H--C--OH

H--C--OH

H

Fatty Acid

Fatty Acid

Fatty Acid

+

H O

H--C--O--C--

O

H--C--O--C--

O

H--C--O--C--

H

Fatty Acid

Fatty Acid

Fatty Acid

Trans and cis fatty acids

PhospholipidsPhospholipids are a class of lipids that are a

major component of all cell membranes as they can form lipid bilayers. Phospholipids contain a diglyceride, a phosphate group and choline.

Built on a glycerol backboneHas at least one fatty acid replaced with

phosphorus containing compoundFound in bodySynthesized by the body as needed

Structure of phospholipids

Functions of PhospholipidsMakes up cell membraneEicosanoid synthesisEmulsifier

Bile acidsLecithins

Hydrophilic end

(attracts water)

Hydrophobic end (attracts lipid)

Emulsification Emulsification refers to the process of dispersing a substance such as oil in an emulsion. It also refers to the process of converting two or more immiscible liquids into an emulsion. During this process, large fat globules are broken down into smaller, evenly distributed particles.

GlycolipidsGlycolipids are lipids with a carbohydrate attached to an -OH of the lipid. Their role is to provide energy and also serve as markers for cellular recognition.

O

(CH2)12CH3

HO

NHCRO

O

H

HO

H

HO

H

HOH

H

OH

a-glucosidebond

a unit of -D-glucopyranose

SterolsSterols, also known as steroid alcohols, are a subgroup of the steroids and an important class of organic molecules. They occur naturally in plants and animals, with the most familiar type of animal sterol being cholesterol. Cholesterol is vital to animal cell membrane structure and function and a precursor to fat-soluble vitamins and steroid hormones.A multi-ringed structureDo not have a glycerol backboneDo not readily dissolve in water

Functions of CholesterolEssential component of

cell membraneProduced by the liverFound only in animal

productsForms important

hormonesEstrogen, testosterone,

vitamin DPrecursor to bile acids

AndrogensAndrogens - male sex hormones

synthesized in the testesresponsible for the development of male

secondary sex characteristics

AndrosteroneTestosteroneO

HOH

H

H3C H

H

H3C H3C

H

HH3C

H

O

HO

EstrogensEstrogens - female sex hormones

synthesized in the ovariesresponsible for the development of female

secondary sex characteristics and control of the menstrual cycle

Progesterone Estradiol

H3C

H

HH3C

H

C=OH

O

CH3OH

HO

H

H

H

H3C

EicosanoidsA group of hormone-like compounds

Regulates blood pressure, childbirth, clotting, immune responses, inflammatory responses, & stomach secretions

By-pass the blood stream and work in the area of origin

Eicosanoids Have Different EffectsOmega-6 eicosanoids; archidonic acid

increase blood clottingincrease inflammatory responses

Omega-3 eicosanoids decrease blood clottingreduce heart attackexcess may cause hemorrhagic stroke

Eicosanoid has different effect on different tissues.

ProstaglandinsProstanoids are a subclass of eicosanoids consisting of the prostaglandins (mediators of inflammatory and anaphylactic reactions), the thromboxanes (mediators of vasoconstriction), and the prostacyclins (active in the resolution phase of inflammation.)

Prostanoic acid

192018

1716

1514

13

78

9

10

1112

65

43

21CO2H

ProstaglandinsProstaglandins are not stored in tissues as

such, but are synthesized from membrane-bound 20-carbon polyunsaturated fatty acids (arachidonic acid) in response to specific physiological triggers

Arachidonic acid1514

89

11 12

6 5CO2H

ProstaglandinsResearch on the involvement of PGs in

reproductive physiology has produced several clinically useful derivatives15-Methyl-PGF2 is used as a therapeutic

abortifacient

15

15-Methyl-PGF2

extra methyl groupat carbon-15

CO2H

HO

HOHO CH3

LeukotrienesLeukotrienes: derived from arachidonic acid

found in white blood cells (leukocytes)an important property is constriction of smooth

muscles, especially in the lungs

L-cysteine

Leukotriene C(its synthesis and release is

triggered by allergic reactions)

NH2

H S

HO H

CO2H

CH2CH2CHCO2-

Thromboxanesderived from arachidonic acidcontain a four-membered cyclic ether within a

six-membered ringinduce platelet aggregation and smooth muscle

contraction

(a potent vasoconstrictor)Thromboxane A2

CO2HO

OH

O

H

H

What are lipoproteins?A lipoprotein is a biochemical assembly that contains both proteins and lipids. The lipids or their derivatives may be covalently or non-covalently bound to the proteins. Examples include the high density (HDL) and low density (LDL) lipoproteins which enable fats to be carried in the blood stream, the transmembrane proteins of the mitochondrion and the chloroplast, and bacterial lipoproteins function of lipoprotein particles is to transport water-insoluble lipids (fats) and cholesterol around the body in the blood.

Classification of Lipoproteins

Atherosclerosis

Summary A knowledge of lipid biochemistry is important in understanding many current biomedical areas of interest e.g. obesity, diabetes, atherosclerosis, and the role of various polyunsaturated fatty acids in nutrition and health.

Content ReviewWhat are some important functions

of the essential fatty acids?How are saturated fatty acids

different from unsaturated fatty acids?

What is esterification?What are the main functions of lipid

in the body?What are emulsifiers?