Overview of Lipid Metabolism

Learning Objectives
By the end of this lecture the students should be able to understand:
Classification of Lipids
The digestion, absorption and utilization of dietary lipids
Lipogenesis and Lipolysis
Lipid malabsorption
The functions of cholesterol
Cholesterol synthesis and metabolism
Cholesterol transport

Classification of lipids

Fatty Acids
Fatty acids are long chain carboxylic acids having a terminal carboxyl
(COOH-) group
Saturated Fatty Acids: have no double bonds e.g. Palmitic acid and
Stearic acid
Unsaturated Fatty Acids: have one or more double bonds
Essential Fatty Acids
Fatty Acids that can not be synthesized de novo and have to supplied
in the diet
Linoleic acid
Linolenic acid

Triglycerides
When one, two or three fatty acids are esterified to a molecule of
glycerol; they form mono, di or triacylglycerols aka TGs
Lipids are stored within adipose tissue as fat droplets made up of TGs

Lipogenesis
Lipid synthesis:
From glycerol derived from Dihydroxyacetone phosphate from
glycolysis
Occurs in the liver and to a small extent in adipose tissue
 Acetyl coA can form any fatty acid except for the essential FA
The main rate limiting enzyme of lipid synthesis is Fatty Acid
Synthase

Lipolysis
Lipid catabolism where lipids become:
Glycerol
Free fatty acids
Glycerol can be converted to pyruvic acid which enters TCA
Fatty Acids are degraded by beta oxidation, occurs in mitochondria of
liver, muscle and adipose tissue

The Dietary Lipids

An adult consumes about 60-150 g of lipid per day
Much of it is composed of Triglycerides
Remaining is made up of free Fatty acids, Cholesterol, cholesterol
esters and phospholipids

Digestion of Dietary Lipids

Digestion begins in the GIT with the action of Lipase
Gastric lipase requires neutral pH to emulsify fat
In adults much of the dietary lipids are transported unchanged to the
small intestine owing to acidic pH of the stomach

Emulsification of Dietary Lipids

In the small intestine the pancreatic secretions digest the dietary lipids
Bile Salts emulsify fat droplets
Pancreatic lipase digests triglycerides into monoglycerides and free
fatty acids
Pancreatic cholesterol esterase digests CE into cholesterol and FFA

Absorption of lipids across intestinal mucosa

FFA, cholesterol and monoacylglycrol together with bile salts,
constitute micelles to get absorbed across the intestinal mucosal cells
 Micelles: amphipathic structures with hydrophobic core containing
the water insoluble lipids, and hydrophilic outer shell soluble in aqueous
medium of intestinal epithelium

Lipid transport from intestinal mucosa

Once inside the intestinal mucosal cells, the absorbed lipids are
resynthesized into TG and CE ( cholesterol esters )
Intestinal cells synthesize apolipoprotein B-48 and package TG and
CE into Chylomicrons
Chylomicrons are secreted first into the lymphatics and then into the
blood
Lipoproteins
TGs and Cholesterol are transported in blood as Lipoproteins.
According to density the lipoproteins are classified as
Chylomicrons
VLDL (very low density lipoproteins )
IDL (intermediate density lipoproteins )
LDL (low density lipoproteins )
HDL (high density lipoproteins )
Classes of lipoproteins with associated Apoproteins
Lipoprotein Function Apoprotein
Chylomicrons Transport dietary TG and CE from intestine to tissues
apoB-48
apoC-II
apoE
VLDL Transport TG from liver to tissues apoB-48
apoC-II
apoE
LDL Delivers cholesterol into cells apoB-100
IDL Picks up cholesterol from HDL to become LDL
Picked up by liver apoE
HDL Picks up cholesterol accumulating in blood vessels apoA1

Lipoproteins and their functions

Complex lipids
Phospholipids
Polar, amphipathic, ionic compounds composed of alcohol attached to
a diacylglycerol or sphingosine
Phosphoglycerides
Phospholipids containing glycerol
Sphingomylin
Phospholipids containing sphingosine
Fatty acid + sphingosine = Ceramide

Glycolipids
Derivatives of ceramide
Components of cell membranes
Serve as receptors of certain bacterial and viral toxins
Antigenic: tumor antigens, embryonal antigens and sources of blood
group antigens

Cholesterol
Component of cell membranes
Steroid synthesis
Precursor of steroid hormones e.g. corticosteroids, aldosterone,
estrogen and testosterone
Vitamin D precursor
bile acid precursor

Fat malabsorption
Syndrome of fat malabsorption consists of Diarrhea, steatorria,
malabsorption, wasting and vitamin deficiencies
Some common causes are:
Lactase deficiecy
Celiac sprue
Pernicious anemia
 Blind loop syndrome
Lymphatic obstruction
Tuberculosis
lymphoma

Deficiencies in Fat malabsorption

Deficiency of Fat soluble vitamins: vitamin A, D, E and K
Iron deficiency-Anemia
Vitamin B12/ Folate deficiency- Megaloblastic anemia
Vitamin K deficiency- easy bruising
Vitamin D deficiency- osteopenia

Cholesterol Metabolism and CVS Function

Cholesterol
The major sterol compose of four fused rings and an eight-membered,
branched hydrocarbon chain
 Functions of Cholesterol
Necessary part of cell membranes
Precursor molecule for steroid synthesis
Aldosterone
Corticosteroids
Estrogens
Progesterone
Testosterone
Bile acid for digestion
Vitamin D

Sources of Cholesterol
 Cholesterol Synthesis

Occurs in cytosol
Requires NADPH and ATP
Highly regulated
80 % in liver, ~10% intestine, ~5% skin
Hydroxymethylglutaryl-coenzyme A (HMG-CoA) is the precursor for
cholesterol synthesis.
HMG-CoA is also an intermediate on the pathway for synthesis of ketone
bodies from acetyl-CoA.
 Formation of HMG CoA-Rate Limiting step
HMG-CoA is formed by condensation of acetyl-CoA & acetoacetyl-
CoA, catalyzed by HMG-CoA Synthase.
HMG-CoA Reductase catalyzes production of mevalonate from HMG-
CoA
O O

H3 C C CH2 C SCoA
H2 O O acetoacetyl-CoA
H3 C C SCoA
acetyl-CoA HMG-CoA
HSCoA Synthase

O OH O

O C CH2 C CH2 C SCoA

CH3
hydroxymethylglutaryl-CoA
 Regulation of Cholesterol Synthesis

Cholesterol Transport
Chylomicrons:
Chylomicrons transport triglycerides from intestine
Very Low Density Lipoproteins (VLDL) and Intermediate Density
Lipoproteins (IDL) :
VLDL produced in liver . Carry cholesterol and triglycerides
Low Density Lipoproteins (LDL)
LDL result from metabolism of VLDL and IDL and carry cholesterol.
LDL are important cause of heart disease
High Density Lipoproteins(HDL)
HDL is good cholesterol. It removes cholesterol and protects against
heart disease
 Cholesterol
Transport

Hypercholestrolemia

Blood Cholesterol levels

Total cholesterol
< 5.17 mmol/L = Good
5.17-6.19 = Borderline High
 > 6.20 = High
LDL
< 2.58 mmol/L = Good
2.58-3.33 = Near Normal
3.34- 4.12 = Borderline High
4.13-4.88 = High
> 4.88 = Very High

Hypercholestrolemia
Hypercholestrolemia-Risk factor for
Atherosclerosis

Atherosclerosis
Hypercholesterolemia and Risk of Stroke

HDL-Cardio protective Lipoprotein

 Management of Hypercholestrolemia
Life style modifications
Balanced diet
Exercise
Stress management
Drug Therapy

REFERENCE
Lippincotts Illustrated Review
Biochemistry
5th Edition
Page no. 219 to 224
THANKS