The lipids

Biochemistry for nurses

THE LIPIDS

Definition of the Lipids

• Biological molecules that are insoluble in aqueous solutions but soluble in organic solvents (methanol, ethanol, ether…) are classified as Lipids.

• Lipids are principally composed by carbon (C), hydrogen (H) and oxygen (O).

• Lipids can be solids as the greases, or liquids as oils


Lipids Functions

• Lipids have 4 major functions in our body:

They are structural components of biological membranes.

They provide energy reserves, mostly in the form of Triglycerides.

They are precursors of vitamins and hormones. They are precursors of bile acids which aid in

lipid absorption during the digestion.


Classification of the Lipids

Lipids are classified according their structures:

• Simple Lipids: Triglycerides, Saturated and Unsaturated Fatty acids

• Compound Lipids: Phospholipids, Sphingolipids.

• Steroids: Cholesterol, Androgens, Estrogens and Adrenal Corticosteroids.


Simple Lipids: Fatty acidsFatty acids are long-chain hydrocarbon molecules containing a carboxylic

acid moiety at one end. There are two types of Fatty acids: Saturated and

Unsaturated. The numbering of carbons in fatty acids begins with the

carbon of the carboxylate group. Ex: Palmitic acid, CH3(–CH2)14–COOH

Fatty acids have two major roles in the body:

1. As the components of more complex membrane lipids.

2. As the major components of stored fat in the form of triglycerides.


Saturated Fatty acidsFatty acids that contain no carbon–carbon double bonds are called “saturated fatty acids”. Each carbon has the maximum atoms of Hydrogen (H), the molecule is saturated. Saturated fatty acids of less than 8 carbon atoms are liquid at physiological temperature (37 °C), whereasthose containing more than 10 are solid.


Unsaturated Fatty acidsFatty acids that contain one or multiple carbon-carbon double bonds are called “unsaturated fatty acids”. The numeric designations used for fatty acids come from the number of carbon atoms, followed by the number of sites of unsaturation (e.g. Palmitoleic Acid is a 16-carbon fatty acid with one unsaturation on carbon 9 and 10, and is designated by 16:1∆9).


Types of Fatty acids

Most of the vegetable oils are rich in unsaturated fatty acids (e.g Colza, Olive

and Corn oils), except for Palm and Coconut oils which are rich in saturated

fatty acids.


Cis and Trans nomenclature The carbon-carbon double bond can adopt two different organization in space: Cis and Trans.

Cis = Hydrogen atoms of the double bond are in the same side.

Trans = Hydrogen atoms of the double bond are in opposite sides.


Essential Fatty Acids The human body is able to synthesize Fatty acids from the Oleic Acid (C18H34O2) however this is not the case with some unsaturated fatty acids of 18 carbons. Consequently, they have to be provided from outside through the diet. They are called “Essential Fatty Acids”.There are two essential fatty acids which cannot be synthesized from precursors in the human body:

Linoleic acid is the precursor of the Omega-6 Fatty acids. It is a compound of the membrane phospholipids and It is involved in the growth and development of the human body.

α-Linolenic acid is the precursor of the Omega-3 Fatty acids. It has an essential role in the synthesis of the cellular membrane, and it is also involved in the growth and development of the human body.


TriglyceridesThe fats are the fatty acid esters of glycerol and are commonly called triglycerides. The Triglycerides are the principal compound of the vegetal oils and the animal fats. In the human body, the Triglycerides are stored in the adipose tissues. The Triglycerides serve three major physiological functions in the human body:1. they are reserve food material (energy supply) 2. They serve as insulation against the loss of body heat3. they are important as padding material to support and protect internal

organs

The Triglycerides are composed by 1 molecule of Glycerol + 3 Fatty Acids joined by ester linkages.

There are two types of Triglycerides: Simple and Mixed.


Simple TriglyceridesSimple triglycerides are composed of a glycerol backbone to which 3 identical fatty acids are esterified.


Mixed TriglyceridesMixed triglycerides are composed of a glycerol backbone to which 3 different fatty acids are esterified.

3 different Fatty Acids joined by ester linkages

Glycerol


Compound Lipids: Phospholipids• The phospholipids are lipids

composed by the assembly of a Glycerol + a Phosphate group + 2 molecules of Fatty acids.

• The Phospholipids are organized in 2 parts: Hydrophobic (non polar tails = doesn’t mix water) and Hydrophilic (polar head = mix water).

• In presence of water, the phospholipids adopt structures in Bilayers sheet or Micelles.

• The cell membranes are bilayers of phospholipids: Hydrophobic part is inside the membrane while the hydrophilic part is outside (surface) the membrane.


Various Phospholipids

The phospholipids are divided in 2 groups: Glycerophospholipids (major) and Sphingophospholipids


SteroidsThe Steroids are organic molecules having a STEROL structure as core structure:

The most abundant and best known steroid is the CHOLESTEROL. Some hormones such as Cortisone, Estrogen and Testosterone are also steroids. These hormones are made from the Cholesterol.


Steroids: CholesterolThe Cholesterol is a lipid having a polar group (hydroxyl group: -OH) and a sterol structure as non polar group.






Cholesterol Functions

• Membrane Component

• Precursor to: Bile Acids Vitamin D Steroid Hormones


CholesterolDespite its bad reputation, Cholesterol is essential to our health:• Cholesterol composes around 35% of the lipids in the animal cell

membranes (there is no cholesterol in the vegetable cell membrane). The fluidity of the membrane is changed according the cholesterol proportion: More there are cholesterol, more the membrane is rigid!


• The Cholesterol is precursor of many others essential molecules such as Steroid Hormones:

BIOSYNTHESIS

Steroid hormones help to control metabolism, inflammation, immune

functions, salt and water balance,

development of sexual characteristics.


Cholesterol is also precursor of Bile Acids and Vitamin D (in LIVER)

BIOSYNTHESIS

The bile acids help to the lipids absorption in the intestine during the digestion

The vitamins D are involved in the Calcium and Phosphorus absorption

in the intestine


Digestion of LipidsLIPIDS are insoluble in aqueous solution

The Triglycerides are not absorbable. The absorbable lipids are:• The Fatty Acids• The Monoglycerides• The Cholesterol

The major steps of the lipids digestion are:

1. Emulsification of Fats by Bile acids2. Hydrolysis of Lipids by enzymes3. Micelles formation by Bile acids4. Absorption by endocytosis of the Micelles content.


Digestion of LipidsThe digestion of lipids involves:1. Bile Acids2. Enzymes: Pancreatic Lipases and Cholesterol Esterase.3. The Micelles formation for the lipids absorption through the

intestinal Brush border.


Emulsification of Fats by Bile acids

• An emulsion is a heterogeneous mixture of two immiscible liquids such as water and oil.

• The emulsification is to disperse one of the substances (Lipids) in the other (water) in the form of very small droplets.

• The mixture remains stable thanks to an emulsifier (Bile Acids) which acts as a surfactant

• The Bile Acids are amphiphilic with a hydrophilic side and a hydrophobic side.• The emulsification makes Lipids accessible to the enzymes for hydrolysis.


Hydrolysis of Lipids

• Triglycerides are hydrolysed in the human body by Pancreatic Lipases to produce free Fatty Acids and Monoglyceride molecules.


Hydrolysis of Lipids

• The Cholesterol ester are hydrolysed in the human body by Cholesterol Esterase to produce a free Fatty Acid and Cholesterol.


Formation of Micelles

The free Fatty Acids, Monoglyceride and Cholesterol, produced by the Lipids Hydrolysis, interact with the Bile Acids to form water-soluble complexes called “Micelles”. Their diameter is 4 to 6 nm.


Lipids Absorption by endocytosis• The free Fatty Acids, Monoglycerides and Cholesterol enter the

Enterocytes of the intestinal Brush border by endocytosis• Triglycerides and Cholesterol esters are re-synthesized inside the

Endoplasmic reticulum• Then there is a combination of these lipids with proteins (apolipoproteins)

to form CHYLOMICRONS


• The Chylomicrons are Lipoproteins

• They are carriers of Lipids

• They reach the lymphatic vessels and then the bloodstream

• The Chylomicrons exist only during the digestion phase

• They have a very short

lifetime in the bloodstream

• Chylomicrons transport the Lipids to the tissues (i.e. adipose, muscular) during the digestion phase.


Summary


Cholesterol transport in the blood• The Cholesterol is a Lipid consequently it cannot be mixed with water• The Cholesterol is transported as Cholesterol Ester • The Cholesterol Ester moves through the bloodstream to tissues by combination with

proteins and phospholipids to form LIPOPROTEIN particles. • More the Lipoprotein has proteins, more its density is high. There are 2 types of

Lipoprotein:1.HDL (High Density Lipoprotein) “Good Cholesterol”2.LDL (Low Density Lipoprotein) “Bad Cholesterol”

HDL and LDL are always present in the Bloodstream


LDL receptor• LDL transport Cholesterol Esters from the LIVER to the Tissues through the Blood

stream. • The Cells have LDL receptors on their surface. • The LDL apolipoprotein link specifically the LDL receptors on the Cell surface.

[Cholesterol] is LOW

[LDL receptor] INCREASES

[Cholesterol] is HIGH

[LDL receptor] DECREASES


LDL and Atherosclerosis

When EXCESS of LDL in the blood gets high

[Oxidized LDL] in the blood increases

Atheromatous plaques formation occurs

Atherosclerosis= Slow and progressive

building up of plaques made of Fatty substances,

Cholesterol and cellular waste products.

We call LDL “Bad Cholesterol”!


Cardiovascular diseasesBlood Clot Formation!!



Classic Heart Attack Symptoms: Nausea, or vomiting Chest pain Difficulty breathing Sweating Pale skin Anxiety


Reverse Cholesterol transport (RCT)• HDL avoids the accumulation of cholesterol in the Blood• HDL pick up the excess cholesterol back to the Liver (Reverse cholesterol

transport)• In the Liver, the excess cholesterol is eliminated into Bile Acids”

We call HDL “Good Cholesterol”!


Education

The lipids