04 lipids of physiological significance_ 10.2011

8/12/2019 04 Lipids of Physiological Significance_ 10.2011

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Lipid Compounds ofPhysiological Significance

By

Amr S. Moustafa, MD, PhD


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Objectives Functions of lipid compounds

Clinical problems

Lipid compounds of physiological importance

Complex lipids:

Phospholipids, glycolipids and lipoproteins


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Functions of lipid compounds

Major energy source for the body

Structural component of cell membranes

Important regulatory molecules:

e.g., Fat-soluble vitaminsSteroid hormonesProstaglandinsSignaling molecules: Inositol triphosphate (IP3)


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Lipids and Related Clinical Problems

Obesity

Atherosclerosis and hypertension

Coronary heart diseases


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Lipid Compounds

Heterogeneous group

Relatively water-insoluble (? Exception)

Soluble in non-polar solvents


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Lipid Compounds:Heterogeneous Group

A. Simple Lipids:

Fatty acidsKetone bodies

Triacylglycerol

Cholesterol

B. Complex Lipids:

Phospholipids

Lipoproteins

Glycolipids


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Free Fatty Acids

Amphipathic: Both hydrophobic & hydrophilic parts


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Free Fatty Acids FFA)1.Chain length:

Short-chain and Medium-Chain

Long-Chain e.g., Palmitic acid 16:0

Very long-chain e.g., Nervonic acid 24:1

2.Degree of saturation:

Saturated: No double bonds

Unsaturated: Mono- or poly-unsaturatedCis- or trans-form

3.Branched Vs straight-chain

4. Essential fatty acids


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Fatty Acids


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Fatty Acids

Saturated Vs Unsaturated

Melting temperature (Tm):Addition of double bonds:

Tm

Increase chain length:

Tm

Kink


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Branched-chain

Fatty acid: Phytanic acid

Milk & dairy

products


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Plasma Fatty AcidsEsterified form (~90%):

Intriacylglycerol, cholesterol ester, phospholipids(as part of lipoproteins)

Free-form (unesterified):

Transported in association with albumin


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Triacylglycerols Storage form in adipose tissue

~ 90% of dietary lipids

Glyscerol plus 3 fatty acids

Blood transport: Chylomicrons and VLDL


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1. Acetone

2. Acetoacetate

3. -Hydroxybutyrate

Ketone Bodies1. Water-soluble

2. Diabetic Ketoacidosis


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A. GlycerophospholipidsGlycerol-containing phospholipids

1. Phosphatidylcholine (Lecithin)

e.g., Surfactant (Dipalmitoylecithin)

2. Cardiolipin (antigenic)3. Phosphatidyl inositol (signaling molecule)

B. Sphingo-phospholipids:Sphingosine-containing phospholipids:

e.g., sphingomyelin (Myelin sheath)

Phospholipids


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Members:1. Phosphatidylcholine

(Lecithin)

e.g., Surfactant

(Dipalmitoyl lecithin)

Phospholipids:A. Glycerophospholipids

Parent Compound

Phosphatidic acid


18/34Diphosphatidyl glycerol


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Intracellular Signaling by Inositol triphosphate


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Phospholipids:B. Sphingo-phospholipids

CH3 (CH2)12 CH CH CH CH CH2O

OH NH

C

O

(CH2

)n

CH3

Long Chain Fatty acid

Phosphorylcholine

Sphingomyelin


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Sphingosine

CH3 (CH2)12 CH CH CH CH CH2OH

OH NH2

Long chain, unsaturated amino alcohol


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Ceramide: Parent Sphingolipid Compound

CH3 (CH2)12 CH CH CH CH CH2OH

OH NH

C

O

(CH2)nCH3



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Sphingomyelin

CH3

(CH2

)12

CH CH CH CH CH2

O

OH NH

C

O

(CH2)nCH3


Phosphorylcholine


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Cholesterol:Structure


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Overview and FunctionsMajorSterol of animal tissuesComponent of cell membranes

Precursor for:

Bile acids & saltsVitamin D

Steroid hormones:

Mineralocorticoids e.g.,Aldosterone

Glucocorticoids, e.g.,Cortisol

Sex hormones, e.g., Testosterone

Estrogen & progesterone

Hypercholesterolemia:Atherosclerosis & CAD


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Cholesterol: Types

Animal sterol:Cholesterol

Plant sterol:-Sitosterol

Poor intestinal absorption

Active transport back to intestinal lumen

Block cholesterol absorptionDietary treatment of hypercholesterolemia

(Trans fatty acid-free margarine)

Animal and plant sterols:


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Cholesterol: TypesFree cholesterol Esterified cholesterol

OH at C3Hydrophobic

Membranes

Plasma

Transport

FreeLess

Found

Less

LDL/HDL

Fatty acidMore

Absent

Most

HDL/LDL

CONTD


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Lipoprotein StructureProtein part: Apoproteins or apolipoproteins

Abbreviations:Apo-A, B, C

Functions:

Structural and transport function

Enzymatic function

Ligands for receptors

Lipid part:According to the type of lipoproteins

Different lipid components in various combinations


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Lipoprotein Structure


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CompositionofLipoproteins

Chylomicrons

Very low density

Lipoprotein (VLDL)

Low density

Lipoprotein (LDL)

High densityLipoprotein (HDL)


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UltracentrifugationofLipoproteins


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Plasma LipoproteinsTriacylglycerol transport:

Chylomicrons: TG ofdietary origin

VLDL: TG ofendogenous synthesis

Cholesterol transport:

LDL: Mainly free cholesterolHDL: Mainly esterified cholesterol


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Take Home MessageLipids are heterogeneous group of compounds

Lipids are relatively water-insoluble

Simple lipids:FFA, TG, Ketone bodies, Cholesterol

Complex lipids:

e.g., Phospholipids, Lipoproteins

Lipids have important physiological functions

Lipid disorders are the basis for common human

diseases, namely obesityand atherosclerosis

04 lipids of physiological significance_ 10.2011

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