LIPIDS AND LIPOPROTEINS

Lipids (Fats)

Are hydrophobic, organic molecules, insoluble in polar solvents (e.g. water) but soluble in non-polar organic solvents (HYDROCARBON)

Chloroform; Ether

Examples of Hydrocarbon

The Cholesterol and Triglycerides

are present in plasma or serum not as free-floating molecules but as part of water-soluble complexes

Lipoprotein

The Cholesterol and Triglycerides are present in plasma or serum not as free-floating molecules but as part of water-soluble complexes

Water, Hydrophilic (polar) head, Hydrophobic (non polar) tails

Chemical Structure of Lipids

Cholesteryl Esters, FFA & TAG

Example of Hydrophobic tails

Free cholesterol & Phospholipids

• are both Hydrophobic & hydrophilic

Cholesterol esters and Triglycerides

hydrophobic lipids ; located in the core of the lipoprotein particle

Free Cholesterol and Phospholipids

hydrophilic lipids ; located on the surface of the polar groups pointing outward.

Lipoprotein

Acts as vehicles for transporting lipids in the aqueous environment of the circulatory system 

Lipoprotein

Constitute the body’s “petroleum industry”

1. Primary source of fuel

2. Provide stability to the cell membrane and allow transmembrane transport

3. Sources of hormones

Biological Roles of Lipids

Primary source of fuel

Fatty acids and glycerol from hydrolysis of Triglycerides enter the TCA cycle to become ATP. 

Provide stability to the cell membrane and allow transmembrane transport

through the blood stream in the form of lipoprotein

Cholesterol

precursor of all steroid hormones (mineralocorticoids, glucocorticoids, sex hormones)

Simple Lipids

• esters of fatty acids (FA) with alcohols

• Neutral fats (triglycerides) 

•  Waxes

Example of Simple lipids

Compound lipids

• esters of FA that contains other groups (e.g. phosphoric acid and carbohydrates group)

Lecithin

Cephalin

Sphingomyelin

under Phospholipids

Cerebrosides

Gangliosides

under Glycolipids

• Cholesterol and its esters

•  steroids

Sterols (Steroid alcohols)

• Vitamin K

• Carotenoids

Substances associated with lipids

1. Absorption Pathway

2. Exogenous Pathway

3. Endogenous Pathway

4. Reverse Cholesterol Pathway

Lipid Metabolism

Lipid Absorption

Lipids (diet e.g. 60g-130g fats, triglycerides) ------Pancreatic Lipase ----into more polar (amphipathic) compounds ingests ---absorbs ---resynthesis --- transports 

Lipid Absorption

needs special membrane for intestinal absorption

Lipid Absorption

• These compounds and bile salts form mixed micelles, in which amphiphatic lipids orient themselves with the hydrophobic regions insides the micelles and polar groups exposed to the aqueous environment

Lipid Absorption

needs special membrane for intestinal absorption

Lipid Absorption

occurs upon contact of micellar solutions of lipid with the microvillus membrane of the mucosal cells.

Triglyceride

• diglyceride, Monoglycerides, FFA

Cholesterol esters

• Free cholesterol

Phospholipids

Lysophospholipids

Exogenous Pathway

• Chylomicrons are synthesized in the intestine, carrying dietary lipids to the circulation 

•  Lipoprotein Lipase (LPL) hydrolyzes triglycerides in the chylomicrons into FA and glycerol or reesterified for long term storage in the hepatic cells 

•  Chylomicrons -  Chylomicron remnant particles

Chylomicrons

are synthesized in the intestine, carrying dietary lipids to the circulation

Lipoprotein Lipase (LPL)

hydrolyzes triglycerides in the chylomicrons into FA and glycerol or reesterified for long term storage in the hepatic cells

Endogenous Pathway

• Triglycerides in the liver are packaged into VLDL, carrying lipids to the circulation 

•  VLDL – converted-à VLDL remnants by action of LPL and taken up by liver 

•  Half of VLDL --- transformed - LDL for delivery of exogenous cholesterol to peripheral cells

Triglycerides in the liver

are packaged into VLDL, carrying lipids to the circulation

VLDL

• converted-à VLDL remnants by action of LPL and taken up by liver 

Half of VLDL

transformed - LDL for delivery of exogenous cholesterol to peripheral cells

Role of HDL

to maintain the equilibrium of cholesterol in peripheral cell

Reverse Cholesterol Transport Pathway

HDL removes excess -- > transport pathway delivers cholesterol to the liver

Aqueous Diffusion Pathway

• HDL acts as a sink for the small amount of Cholesterol that can diffuse away from the cells.

ABC A1 transporter

• pumps various ligands across the plasma membrane; transfers lipid to plasma membrane - enabling ApoA1 to bind cell membrane.

Lipolysis

breaking down or hydrolysis of triglycerides or fats to FA or glycerol

Lipogenesis

synthesis of lipids from glucose and other intermediate compounds like pyruvate and acetyl CoA.

Plasma Lipids

• Composed of mostly carbons-hydrogen (C-H) bonds

1. Fatty Acids

2. Triglycerides

3. Cholesterol

4. Phospholipids

5. Glycolipids

Major Lipids in the Plasma

Triglycerides

most prevalent fats in the diet.

Cholesterol

HDL/LDL

VLDL, HDL, LDL

Transported by lipoproteins

Unesterified Fatty Acids

bound to albumin

Esterified Fatty Acids

• constituent of triglycerides or phospholipids

Fatty Acids

Mainly derived from hydrolysis of triglycerides in adipose tissues

4-6 Carbon atoms

Short Chain FA

8-12 atoms

Medium Chain FA

>12 C atoms

Long chain FA

Monounsaturated

One double ring

Polyunsaturated

more than one double ring

1. FA are very important sources of energy

 2. Provide the substance for conversion to glucose (Gluconeogenesis)

Functions of FA

Phospholipids

• Most abundant lipids derived form phosphatidic acid

Phospholipids

• Participate in cellular metabolism and blood coagulation

Phospholipids

Originate in the liver and intestines.

Phospholipids

• Produced from the conjugation of 2 Fatty acids and a phosphorylated glycerol 

Phospholipids

Structure is similar with Triglycerides except that they contain 2 FA

Phospholipids

• The two fatty acids attached to one molecule of glycerol

Phospholipids

• Third position contain phospholipid head groups

Phospholipids

• Found on the surface of lipid layers, major constituents of cell membranes and outer shells of lipoprotein molecules

Cholesterol (3-hydroxy-5, 6-cholestene)

• Unsaturated steroid alcohol containing four rings with high molecular weight 

Cholesterol (3-hydroxy-5, 6-cholestene)

• Is found almost exclusively among animals (all cells and some body fluids)

Cholesterol (3-hydroxy-5, 6-cholestene)

• Is not catabolized by most cells, does not serve as a source of fuel/ energy

Estrogen

Cholesterol’s transport and excretion is promoted by ________.

Cholesterol

• For manufacture and repair of cell membrane

Cholesterol

• Synthesis of bile salts (promote fat absorption in the intestine) 

• Precursor steroid hormones (glucocorticoids, mineralocorticoid, progesterone, androgen estrogen)

Cholesterol Pool

excess intake of AA, CHO and Fatty acids

Diet

small amount is absorbed from meat and dairy products

Synthesis of Vitamin D

• converted to 7- dehydrocholesterol and transformed to Vit D3 in the skin by irradiation from sunlight

Cholesteryl Esters

• 70% of total Chole (plasma / serum)

•  Bound to a Fatty Acid

• Undergoes esterification by LecithinCholesterol Acyl Transferase (LCAT)

• Since it is not charged; it is classified as neutral lipids and found in the center of the lipoproteins along with triglycerides

Free Cholesterol

• 30%

• Found in serum, plasma and RBCs

•  the Unesterified cholesterol

• Active form of cholesterol with cytotoxic property.

• FC and Phospholipids (with hydrophilic property) are found on the surface of lipoCHON

• Synthesized in the liver

• Carry out biosynthesis in skin, adrenal glands, intestine

• Secreted unchanged in bile

•  Absorption is enhanced by bile and pancreatic juice

•  Excreted through the bile, feces and urine

Synthesis of Cholesterol

• Late half pregnancy

• Hypothyroidism

• Untreated diabetes

• Ketosis

• Heart diseases 

Increased Cholesterol

• Newborn and infants

• Severe anemia

• Prolonged wasting diseases

• Hepatic cellular damage

• Malabsorption

• Old age

Decreased Cholesterol

Triglycerides/Triglycerol (Neutral Fat)

• Contain three fatty acids attached to one molecule of glycerol by ester bonds 

• Contain saturated fatty acids or unsaturated FA No charged groups, water insoluble, neutral lipid

•  Main storage form of lipids in human (Adipose Tissue) ; constitutes 95% of stored fat and the predominant form of glyceryl ester found in plasma

Triglycerides

• Provides excellent insulation to vital organs in the form of fat deposits (adipose tissue)

•   Breakdown is facilitated by lipase, lipoprotein lipase, epinephrine and cortisol

Exogenous Source, Endogenous Source

2 Sources of Triglycerides

Exogenous source (Diet)

From Animal (saturated fatty acid) – tends to be solids at room temperature 

From plants (unsaturated fatty acid) – tends to be liquid at room temperature 

Endogenous source

• synthesized in the liver and other tissues

• High energy triglyceride molecules (95% of fats stored in adipose tissues) 

• are transported in plasma mostly in the form of large triglyceride-rich lipoproteins (Chylomicrons and VLDL)

lipids and proteins (apolipoproteins)

Components of Lipoprotein

Free cholesterol, phospholipids, triglycerides, cholesteryl esters

Composition of Lipoprotein

Free cholesterol. phospholipids

Composition of lipoprotein that are found on the surface

Triglycerides and cholesteryl esters

Composition of Lipoprotein that are found in the core regions

Lipoprotein

• Are roughly spherical complexes of water insoluble dietary lipids and watersoluble proteins with a design uniquely suited to transport lipids throughout the body.  

• facilitate the metabolism of lipids in the hydrophilic environment of the circulatory system 

• Maybe classified by either density or their electrophoretic ability

•   Chylomicrons, VLDL, LDL and HDL 

•  Differ in their chemical composition, size and potential atherogenicity

• Transfer and accept lipid and protein components to and from other lipoproteins and tissues  

• Are subjected to actions of plasma and tissue enzymes 

• Are removed from circulation through receptor-mediated uptake

• Decreased DENSITY of Lipoprotein

• Increased triglycerides 

• Decreased protein content (ApolipoCHON)

General Rule of Lipoproteins