Lecture 13: Lipids

Overview

• Lipids

• Biologically Active Lipids

• Lipid Biosynthesis

• Lipid Derivatives

• Cholesterol

Lipids

• Organic molecules with low water solubility (hydrophobic).

• Grouped into 8 classes including soaps, free fatty acids, and complex lipids.

Biological Functions of Lipids

Chemical Functions

• Membrane structure

• Efficient energy storage

• Cofactors

• Signaling molecules

• Antioxidants

Physical Functions

• Insulation

• Absorption of heat and shock

• Water repellent properties

• Protection against water loss

• Pigments (e.g., in tomatoes, carrots, pumpkins, some birds)

• Buoyancy in marine mammals

Lipid Classification

• Non-fatty Acid Lipids: Cholesterol, terpenes, etc.

• Fatty Acid Lipids:

  • Complex lipids: further divided into storage lipids (fats, oils, waxes) and membrane lipids.

Fatty Acids

• Storage lipids with carboxylic acid structure, containing 4-36 carbon atoms.

• Characteristics of fatty acids:

  • Saturated: no double bonds

  • Monounsaturated: one double bond

  • Polyunsaturated: multiple double bonds

• Examples:

  • Oleic acid (monounsaturated, found in olives, avocados)

  • EPA (polyunsaturated, found in fish)

Fatty Acid Properties

• Solubility decreases with chain length.

• Melting point increases with chain length and saturation level.

• Saturated chains adopt extended conformations while unsaturated chains commonly adopt cis conformations, causing kinks.

Fats for Fuel Storage

• Fats carry more energy per carbon than sugars and hold less water, making them efficient for long-term storage.

• Types of adipose tissue:

  • White fat (adipocytes): single lipid droplet for energy storage.

  • Brown fat: multiple lipid droplets, rich in mitochondria and capillaries, involved in thermogenesis.

Fatty Acids and Health

• Omega-3: alpha-linolenic acid (ALA) from seeds, nuts, plants, and fish oil; precursor of EPA and DHA.

• Omega-6: gamma-linolenic acid (GLA); high ratios associated with increased cardiovascular risk.

• Recommended omega-6 to omega-3 ratio is 1:1 to 4:1; North American average is significantly higher.

Trans Fatty Acids

• Trans bonds allow fatty acids to adopt a more stable form with higher melting points than cis forms.

• Naturally occurring trans fats are found in meat; artificial trans fats formed during hydrogenation can lead to health risks.

Triacylglycerols

• Majority of body fat is in the form of triacylglycerols (triglycerides); less soluble due to lack of charged groups.

• Comprised of glycerol and three fatty acids, primarily stored in liver and adipose tissue.

Triacylglycerol Regulation

• Formation activated by insulin; breakdown activated by glucagon and epinephrine.

• 75% of fatty acids are reconverted to triacylglycerols, providing energy reserves.

Waxes

• Esters of long-chain fatty acids and long-chain alcohols; used for protection, waterproofing, and storage.

Structural Lipids

Glycerophospholipids

• Major constituents of cell membranes, made in the smooth endoplasmic reticulum.

• Comprised of two fatty acids linked to glycerol and a polar head group.

Sphingolipids

• Contain sphingosine with an amide linkage, important for signaling and cell recognition.

Biologically Active Lipids

• Play essential roles in signaling; include cholesterol, hormones, vitamins, etc.

Cholesterol

• Four fused ring structure, thickens plasma membrane, obtained from diet or synthesized in the liver.

Steroid Hormones

• Derived from cholesterol, include sex hormones synthesized in gonads, affecting various physiological functions.

Signaling Lipids

• Eicosanoids derived from arachidonic acid; include prostaglandins and thromboxanes which play crucial roles in inflammation and clotting.

Lipid Biosynthesis

• Fatty acid synthesis occurs in cytosol; involves converting Acetyl-CoA to fatty acids through a multi-step process.

• Fatty acid synthase facilitates elongation of fatty chains.

Regulation of Fatty Acid Synthesis

• Stimulated by high energy levels, regulated by Acetyl-CoA carboxylase.

Cholesterol Synthesis and Regulation

• Involves multiple intermediates with insulin and glucagon affecting the activity of HMG-CoA reductase, a key enzyme for cholesterol synthesis.

Lipoprotein Particles

• Carry cholesterol and lipids through circulation; include different densities of lipoproteins serving distinct roles in cholesterol transport.

Cardiovascular Health

• High levels of LDL are correlated with increased risk of heart disease; HDL levels are inversely correlated with cardiovascular risk.

Statin Drugs

• Competitive inhibitors of HMG-CoA reductase, effectively lower serum cholesterol and reduce heart disease risk.