Download Overview of Lipid Metabolism

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
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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
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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 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
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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
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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