Biochem 9.1 Energy Storage Lipids PDF

# Chapter 9: Lipids ## Lesson 9.1: Energy Storage Lipids ### Introduction - After proteins, carbohydrates, and nucleic acids, lipids are the fourth and final major class of biological macromolecules. - Lipids have diverse functional roles, reflected in their varied structures. - This lesson focus...

# Chapter 9: Lipids ## Lesson 9.1: Energy Storage Lipids ### Introduction - After proteins, carbohydrates, and nucleic acids, lipids are the fourth and final major class of biological macromolecules. - Lipids have diverse functional roles, reflected in their varied structures. - This lesson focuses on energy storage lipids, while structural and signaling lipids are discussed in other lessons. ### 9.1.01 General Properties of Lipids - Lipids are defined by their hydrophobicity and insolubility in water. - They contain few polar functional groups relative to their size. - In an aqueous solution, water can only interact with the hydrophobic portions of a lipid through weak London dispersion forces. - This causes water molecules to form strong hydrogen bonds with each other instead, creating a solvation layer around the lipid. - The inability of water to strongly interact with a lipid restricts water’s rotational freedom and leads to low entropy. - Because systems with higher entropy are favored, lipids and other hydrophobic molecules tend to aggregate in aqueous solutions. - The forces leading to this hydrophobic aggregation are **hydrophobic interactions**, which are a crucial driver of protein folding and the organization of structural lipids into membranes and storage lipids into lipid droplets. - **Dispersed lipids** have high order and low entropy, with no strong interactions between lipid and water. - **Aggregated lipids** have less order and higher entropy, as attractive forces within a lipid droplet are weak London dispersion forces. ### 9.1.02 Fatty Acids - The main energy storage lipid is the **triglyceride**, composed of three fatty acids esterified onto a glycerol backbone. - **Fatty acids** are carboxylic acids with an aliphatic (nonaromatic) hydrocarbon R group. - The carboxylic acid (carboxylate at physiological pH) is hydrophilic, while the hydrocarbon "tail" of longer fatty acids provides hydrophobic character. - This makes fatty acids **amphipathic** molecules, with both hydrophilic and hydrophobic character. - A common mistake when counting carbons in a line-angle structure of a fatty acid is to forget the carboxylate carbon. - The fatty acid shown in Figure 9.3 has a 16-carbon chain, with numbering starting from the carboxylate carbon as carbon 1. - Greek letter designations are also used: carbon 2 = α-carbon, carbon 3 = β-carbon, carbon 4 = γ-carbon, and the final carbon = ω-carbon. - Fatty acids can vary greatly in structure, including in number of carbons and unsaturation. - Long-chain fatty acids have 13 or more carbons, medium-chain have 7 to 12 carbons, and short-chain have 6 or fewer carbons. - Most important fatty acids in human metabolism have an even number of carbons, but odd-chain fatty acids exist as well. - **Saturated fatty acids** have no carbon-carbon double bonds in their hydrocarbon tail. - **Unsaturated fatty acids** have at least one carbon-carbon double bond in their hydrocarbon tail. - In natural fatty acids, these double bonds are typically in the *cis* configuration, which provides a "kink" in the fatty acid tail. - Fatty acids may have multiple double bonds, but they are typically not conjugated, meaning at least one sp³ hybridized methylene group (-CH2-) is between any pair of double bonds. - Many fatty acids are classified based on the ω numbering of the double bond nearest the ω-end. - The polyunsaturated fatty acid in Figure 9.6 has a double bond at position 9 (ω-9) and another at position 12 (ω-6), making it an ω-6 fatty acid. - Fatty acids are highly reduced molecules compared to other energy molecules, such as carbohydrates. - This allows them to store a lot of energy that can be released upon oxidation. - During **β-oxidation** in the mitochondria or peroxisome, carbons 1 and 2 form acetyl-CoA and the β-carbon is oxidized. ### 9.1.03 Triacylglycerides - Typically, fatty acids are stored in triglycerides, where they are hydrolyzed when needed and released as **free fatty acids (FFA)** into the bloodstream. - FFA must bind to carrier proteins like albumin to reach target tissues for processing. - Fatty acids are amphipathic, so they do not aggregate into lipid droplets but form micelles. - However, micelles are too small to store large amounts of fatty acids. - To store fatty acids in a large lipid droplet, the carboxylate group must be made hydrophobic by esterifying it with an alcohol. - In storage lipids, fatty acids are typically esterified onto **glycerol**, a three-carbon compound with an -OH group on each carbon. - If all three hydroxyl groups are esterified with fatty acids, the resulting molecule is a **triacylglycerol** (also called a **triglyceride**). - Esterification results in a less polar molecule, making it easier to store in lipid droplets. - Glycerol is prochiral, meaning it is not chiral itself but can become chiral through chemical reactions. - The triglyceride becomes chiral if the fatty acids esterified onto carbon 1 and carbon 3 are different. - Upon mobilization, the ester linkages in a triglyceride are hydrolyzed, yielding free fatty acids and glycerol. - Free fatty acids enter the bloodstream, bind to albumin, and are oxidized in target tissue. - Glycerol can enter glycolysis or gluconeogenesis. - While albumin can transport free fatty acids, it cannot transport intact triglycerides. - Instead, intact triglycerides are transported via **lipoprotein particles** (chylomicrons, HDL, LDL). - Lipoprotein particles are similar to large lipid droplets, but with characteristic proteins embedded in their surface that target each particle to the correct tissue.