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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 AcidsFatty 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 acidUnsaturated 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

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Linolenic acid

TriglyceridesWhen 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

LipogenesisLipid synthesis:

From glycerol derived from Dihydroxyacetone phosphate from

glycolysis

Occurs in the liver and to a small extent in adipose tissueAcetyl coA can form any fatty acid except for the essential FA

The main rate limiting enzyme of lipid synthesis is Fatty Acid

Synthase

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LipolysisLipid 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 LipidsAn adult consumes about 60-150 g of lipid per day

Much of it is composed of TriglyceridesRemaining is made up of free Fatty acids, Cholesterol, cholesterol

esters and phospholipids

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Digestion of Dietary LipidsDigestion 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 LipidsIn 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 mucosaFFA, 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 inaqueous medium of intestinal epithelium

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Lipid transport from intestinal mucosaOnce 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 asChylomicrons

VLDL (very low density lipoproteins )

IDL (intermediate density lipoproteins )

LDL (low density lipoproteins )

HDL (high density lipoproteins )

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Classes of lipoproteins with associated ApoproteinsLipoprotein 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

LDLPicked up by liver

apoE

HDL Picks up cholesterol accumulating in blood

vessels

apoA1

Lipoproteins and their functions

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Complex lipidsPhospholipids

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

GlycolipidsDerivatives 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

CholesterolComponent of cell membranes

Steroid synthesis

Precursor of steroid hormones e.g. corticosteroids, aldosterone,

estrogen and testosterone

Vitamin D precursor

bile acid precursor

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Fat malabsorptionSyndrome 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 malabsorptionDeficiency 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

cvs week 1

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