LipidLipidss

Dr. Sooad Al-DaihanDr. Sooad Al-DaihanBiochemistry department Biochemistry department

LipidsLipids

Heterogeneous group of biomolecules.

Water insoluble (hydrophobic).

Soluble in organic and non-polar solvents acetone, ether, chloroform and benzene.

Classes of lipids

Conjugated (complex) lipids

Derived lipids

- Triglycerides- Waxes -Phospholipids,

- Glycolipids- Sphingo- phospholipids- Lipoproteins.

-Fatty acids-Cholesterol-Ketone bodies

Esters of FA with alcohols

Esters of FA with alcohols and additional group

Obtained on hydrolysis of simple or complex lipids

Simple lipids

Major source of energy source of energy for the body: Fat stored in the adipose tissue is a

direct and potential source of energy.

1 gm lipids 9.3 Kcal

1 gm CHO 4.1 Kcal

Storage form of energy-triglyceridetriglyceride

Serve as structural components structural components of cell membrane (PLs, glycolipids).

Some are hormoneshormones e.g. steroid hormone (cortisol, aldosterone, sex

hormones).

Essential in the diet Essential in the diet to provide the body with some essential FA and of fat-

soluble vitamins (A, D, E,K) which have regulatory or coenzyme function

FunctionsFunctions

An adult man eats about 100-150 g100-150 g of lipids/day

The main lipids in diet are TG which constitute most of fat and oils we eat, but diet contains also some cholesterol and phospholipids

Digestion and Absorption of Lipids

STEP 3STEP 3Liver releases bile acids to solubilize lipid products in mixed micelles

STEP 2STEP 2Pancreas releases:Lipase (+colipase)cholesterol esterasephospholipase A2

Lipids:Lipids:TriacylglycerolsCholesterol estersPhospholipids

pancreaspancreas

liverliver

STEP 4Lipids absorbed from micelles into epithelial cells

STEP 5STEP 5Chylomicrons form and travel through lymphatics

Gastric Lipase

STEP 1STEP 1

small intestinesmall intestine

stomachstomachpHopt ~5, Initiates hydrolysis and acts on TG with short chain FAs

Lingual lipase begins emulsification of lipids and PLs (negligible)

Lipid emulsificationLipid emulsification

Bile acids help emulsifying fat droplets thus increasing their surface area

Pancreatic lipasePancreatic lipase

Pancreatic lipase, also known as pancreatic triacylglycerol lipase, is secreted from the pancreas, and is the primary lipase (enzyme) that hydrolyze dietary fat molecules in the human digestive system.

converting TG to monoacylglycerol and free fatty acid.

Triacylglycerol + 2 H2O 2-monoacylglycerol + 2 fatty acid

Unlike some pancreatic enzymes that are activated by proteolytic cleavage (e.g. trypsinogen), pancreatic lipase is secreted in its final form.

However it only becomes efficient in the presence of colipasecolipase in the duodenum.

Glycerol + two fatty acids + phosphorus

Phosphorus part makes it soluble in water

Fatty acids make it soluble in fat

Therefore can serve as an emulsifier

Key role is in cell membranes

CH2 – O – C - R1

CH2 – O – P – O - X

R2 - C - O - CH

O-

O

O

O

O

PhospholipidPhospholipid

Is secreted by the pancreas into the intestine where it is activated by trypsin and its activity requires the presence of bile salts and calcium ions.

Phospholipase A2

A phospholipase is an enzyme that hydrolyzes Phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D, distinguished by the type of reaction which they catalyze:

I. Phospholipase A Phospholipase A1-cleaves the SN-1 acylchain. Phospholipase A2- cleaves the SN-2 acylchain.

Phospholipase B - cleaves both SN-1 and SN-2 acylchain. Phospholipase C - cleaves before the phosphate, and a phosphate- releasing diacylglycerol containing head

group. Phospholipase D - cleaves after the phosphate.

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The end product of lipid digestion are:MGFA (short FA C4-C10; long chain FA C12-C18)GlycerolLysoPLCholesterol

Absorption of LipidsAbsorption of Lipids

Absorption of lipidsAbsorption of lipids

MGFA

LysoPLCholesterol

+Bile SaltsMicelles

Bile Salts

Cholesterol

LysoPL

Chylomicrons

MG

Long chain FATG

Glycerol

Short chain FA

Glycerol

Short chain FA

Protein

LUMENINTESTINAL WALL

Systematic

Circulation

Th

oracic D

uct

HOHO

O

R

HOHO

O

R

HOHO

(No need for bile acids)

PL

Absorption of lipidsAbsorption of lipids

Short chain fatty acids and glycerol are water soluble and pass via the portal system directly to the liver

Other lipid are water insoluble. They combine with bile salts to form a water soluble complex called micelles which enter the mucosal cells

(move down concentration gradient passive diffusion)

Bile salts are reabsorbed to the liver again

Long chain fatty acid are activated in the mucosal cells and combine with monoglycerols again to reform triglycerides

The TG, PL, and cholesterol combine with protein forming chylomicrons which enter the circulation via lacteals and thoracic duct

Body tissues can extract whatever fat they need from chylomicrons

After absorption, lipids are either oxidized mainly in the liver or are stored in the depot (adipose tissue)

Fate of Dietary Lipids

TG in chylomicron are degraded to glycerol + FFA by Lipoprotein lipase in the luminal surface of capillary bed.

Lipoprotein LipaseFFA + Glycerol

Taken up by liver

• Taken up by peripheral tissues (muscles, adipocytes)• May bind to albumin and transported to other cells

Chylomicron remnants

Taken up by liver

TGChylomicron

1. Tissue lipids Included in the structure of the cell e.g. Cell membrane and

mitochondria.

Never be oxidized to give energy.

Appears as a yellow droplets in the cytoplasm of adipose tissue cells

Body lipids are 2 types: Tissue lipids depot fat (adipose tissue)

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Sites:Sites: Under skin and breast. Around important organs e.g. kidneys. In the omentum and mesentery.

Composition:Composition: Mainly TG which contains saturated and unsaturated. Fas Contains also a little of PLs and cholesterol

Sources:Sources: Absorbed Fat Carbohydrates by lipogenesis

Functions:Functions:

Important source of energySupports some of the internal organs like the kidney.7-dehydrocholesterol present in adipose tissue gives Vit D3 on exposure to UV rays.Protection of bony prominence.Protection against cold,

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In animal that are in caloric balance, the stored TG in adipose tissue is continuously undergoing lipolysis

and reesterification

Metabolism of adipose tissue

FAFA

Glycerol

Lipolysis

FA esterification

Triglycerides

Glycerol-3P

Glucose, amino acids, lactate, pyruvate

FA

Adipocyte

If the rate of lipolysis is more excessive than the rate of reestirification, FFAs accumulate and diffuse into the plasma, where they bind to serum albumin and

are transported to tissue for oxidation

Metabolism of adipose tissue

FAFA

Glycerol

Lipolysis

FA esterification

FA

Glycerol

Triglycerides

Glycerol-3P

Glucose, amino acids, lactate, pyruvate

FA

Adipocyte

Blood

Tissues

Albumin

This occurs in condition where the need for energy is increased as in

.1Starvation

.2Diabetes mellitus

.3During growth

.4Low carbohydrate diet

.5Certain infectious disease as tuberculosis

Causes of excessive lipolysis

Lipolysis is carried out by a number of lipase enzymes which are present in adipose tissue

.1Hormone Sensitive triacyglycerol Lipase (HSL)

.2Diacylglycerol lipase

.3Monoacylglycerol lipase

Mechanism of lipolysis

TG DAG + FFA HSL

DAG MAG + FFADAG lipase

MAG glycerol + FFA MAG lipase

FAFA

Glycerol

Lipolysis

FA esterification

FA

Glycerol

Triglycerides

Glycerol-3P

Glucose, amino acids, lactate, pyruvate

FA

Tissues

Albumin Glycerol-3P

GlyconeogenesisGlycolysisLipogenesis

oxidation

FA

ATP

Blood

Adipocyte

(fasting)(Stress)

Insulin

Hormonol regulation of HSL in adipose cells

(In feeding)+

+

IntroductionIntroduction Lipid breakdown is the process by which a

molecule of fatty acid is degraded by the sequential removal of 2C units, producing acetyl CoA which can then be oxidized to CO2 and H2O by the TCA cycle.

It occurs in many tissues, especially liver and muscle.

Certain tissues such as brain, RBCs, and adrenal medulla are unable to oxidize fatty acids ( because they lack the necessary enzymes)

The Four Stages of Lipid Breakdown

1. Hydrolysis of TAG by Lipase (Lipolysis)

2. Activation of Fatty Acids3. Transport into Mitochondria4. β-Oxidation

LipolysisIt occurs in the cytosol of adipose cells.

TAG is converted into glycerol and 3 fatty acids in 2 steps:

1.A hormone- sensitive lipase hydrolyses TAG at the C1 and C3 positions to form monoglycerol.

2.A monoglycerol specific lipase removes the remaining fatty acid.

Continue .. Glycerol produced cannot

be metabolized by adipose tissue because it does not contain glycerol kinase.

Glycerol is transported to the liver where it is phosphorylated, either to be used again to make TAG or to be converted to dihydroxyacetone phosphate (DHAP), a glycolytic intermediate.

The free F.As produced are either re-esterified to TAG in the adipose tissue or travel in the blood to be taken up by the cells for oxidation.

Hormonal regulation of TAG degradation in the adipocyte .

Activation of Fatty Acids Fatty acids must be esterified to Coenzyme A before they can

undergo oxidative degradation, be utilized for synthesis of complex lipids, or be attached to proteins as lipid anchors.

Acyl-CoA Synthases (Thiokinases) of ER & outer mitochondrial membranes catalyze activation of long chain fatty acids, esterifying them to coenzyme A.

This process is ATP-dependent.

There are different Acyl-CoA Synthases for fatty acids of different chain lengths. 

PPi is cleaved by pyrophosphatase to 2 inorganic phosphate (2Pi)

Transport of Fatty Acyl CoA into Mitochondria

Fatty acyl CoA is impermeable to inner mitochondrial membrane while enzymes for β-oxidation are present in the mitochondria

Therefore after activation, the fatty acid (fatty acyl CoA) interacts with carnitine which helps in its translocation across the inner mitochondrial membrane.

Transfer of the fatty acid moiety across the mitochondrial inner membrane involves carnitine.

Carnitine Palmitoyl Transferases catalyzes transfer of a fatty acid between the thiol of Coenzyme A and the hydroxyl on carnitine

Carnitine-mediated transfer of the fatty acyl moiety into the mitochondrial matrix is a 3-step process: 1. Carnitine Palmitoyl Transferase I, an enzyme on the cytosolic surface of the outer mitochondrial membrane, transfers a fatty acid from CoA to the OH on carnitine. 2.Carnitine acylcarnitine translocase in the inner mitochondrial membrane mediates exchange of carnitine for acylcarnitine. 3.CarnitinePalmitoylTransferaseII,an enzyme within the matrix,transfers the fatty acid from carnitine to CoA. (Carnitine exits the matrix in step 2) The fatty acid is now esterified to CoA in the matrix