Download Lipids

Lipids
Dr. Sooad Al-Daihan
Biochemistry department
Lipids
 Heterogeneous group of
biomolecules.
 Water insoluble (hydrophobic).
 Soluble in organic and non-
polar solvents acetone, ether,
chloroform and benzene.
Classes of lipids
Simple lipids
- Triglycerides
- Waxes
Conjugated (complex)
lipids
-Phospholipids,
- Glycolipids
- Sphingo- phospholipids
- Lipoproteins.
Esters of FA
with alcohols
Derived lipids
-Fatty acids
-Cholesterol
-Ketone bodies
Obtained on hydrolysis of
simple or complex lipids
Esters of FA with alcohols and additional group
Functions
 Major 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-triglyceride
 Serve as structural components of cell membrane (PLs, glycolipids).
 Some are hormones e.g. steroid hormone (cortisol, aldosterone, sex
hormones).
 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
Digestion and Absorption of Lipids
 An adult man eats about 100-150 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
Lingual lipase begins
emulsification of lipids
and PLs (negligible)
Lipids:
Triacylglycerols
Cholesterol esters
Phospholipids
STEP 1
Gastric Lipase
STEP 2
Pancreas releases:
Lipase (+colipase)
cholesterol esterase
phospholipase A2
STEP 3
Liver releases bile acids
to solubilize lipid
products in mixed
micelles
stomach
pancreas
liver
pHopt ~5, Initiates
hydrolysis and acts on TG
with short chain FAs
small intestine
STEP 4
Lipids absorbed from
micelles into epithelial
cells
STEP 5
Chylomicrons form and travel
through lymphatics
Lipid emulsification

Bile acids help emulsifying fat droplets thus increasing
their surface area
Pancreatic 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 colipase in the
duodenum.
Phospholipid
 Glycerol + two fatty acids + phosphorus
 Phosphorus part makes it soluble in water
 Fatty acids make it soluble in fat
O
 Therefore can serve as an emulsifier
 Key role is in cell membranes
O
CH2 – O – C - R1
R2 - C - O - CH
O
CH2 – O – P – O - X
Phospholipase A2
O-
 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.
Continue
 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.
II.
Phospholipase B - cleaves both SN-1 and SN-2 acylchain.
III. Phospholipase C - cleaves before the phosphate, and a phosphatereleasing diacylglycerol containing head group.
IV. Phospholipase D - cleaves after the phosphate.
Absorption of Lipids
The end product of lipid digestion are:
 MG
 FA (short FA C4-C10; long chain FA C12-C18)
 Glycerol
 LysoPL
 Cholesterol
INTESTINAL
WALL
LUMEN
Glycerol
Glycerol
Short chain FA
Short chain FA
(No need for bile acids)
Thoracic
Duct
Chylomicrons
Protein
PL
HO
O
HO
R
Systematic
R
MG
FA
LysoPL
Cholesterol
Long chain FA
MG
Cholesterol
HO
Circulation
O
T
G
Bile Salts
LysoPL
Absorption of lipids
+
Micelles
Bile Salts
Absorption 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 Lipase
Chylomicron
TG
Chylomicron
remnants
Taken up by
liver
FFA + Glycerol
Taken up by liver
• Taken up by peripheral
tissues (muscles, adipocytes)
• May bind to albumin and
transported to other cells
Body lipids are 2 types:
 Tissue lipids
 depot fat (adipose tissue)

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
Continue…
Sites:
 Under skin and breast.
 Around important organs e.g. kidneys.
 In the omentum and mesentery.
Composition:
 Mainly TG which contains saturated and unsaturated.
 Fas Contains also a little of PLs and cholesterol
Sources:
 Absorbed Fat
 Carbohydrates by lipogenesis
Continue…
 Functions:
 Important source of energy
 Supports 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,
Metabolism of adipose tissue
In animal that are in caloric balance, the stored TG in 
adipose tissue is continuously undergoing lipolysis
and reesterification
Adipocyte
Glycerol
Lipolysis
FA
FA
FA
Triglycerides
FA
esterification
Glycerol-3P
Glucose, amino acids,
lactate, pyruvate
Metabolism of adipose tissue
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
Glycerol
Tissues
Adipocyte
FA
Glycerol
Albumin
Lipolysis
FA
FA
FA
Triglycerides
FA
esterification
Glycerol-3P
Blood
Glucose, amino acids,
lactate, pyruvate
Causes of excessive lipolysis
This occurs in condition where the need for 
energy is increased as in
Starvation
Diabetes mellitus
During growth
Low carbohydrate diet
Certain infectious disease as tuberculosis
.1
.2
.3
.4
.5
Mechanism of lipolysis
Lipolysis is carried out by a number of lipase 
enzymes which are present in adipose tissue
Hormone Sensitive triacyglycerol Lipase (HSL)
Diacylglycerol lipase
Monoacylglycerol lipase
TG
HSL
DAG + FFA
DAG
DAG lipase
MAG + FFA
MAG
MAG lipase
glycerol + FFA
.1
.2
.3
Lipogenesis
Glycolysis
Glyconeogenesis
Glycerol
Tissues
b oxidation
FA
Glycerokinase
FA
Albumin
Glycerol
Glycerol-3P
Lipolysis
Adipocyte
ATP
FA
FA
FA
FA
esterification
Triglycerides
Glycerol-3P
Blood
Glucose, amino acids,
lactate, pyruvate
Hormonol regulation of HSL in
adipose cells
(Stress)
(fasting)
+
+
Insulin
(In feeding)
Introduction
 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 Acids
3. Transport into Mitochondria
4. β-Oxidation
Lipolysis
 It 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 reesterified 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