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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

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 apoB-48


intestine to tissues 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 apoE
LDL
Picked up by liver

HDL Picks up cholesterol accumulating in blood apoA1


vessels

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