Lipid Metabolism Overview

Lipids are organic compounds insoluble in water, but soluble in non-polar solvents like benzene, acetone, and petroleum ether. Complex lipids are formed by monomers linked via ester bonds.

Fatty acids are classified by the number of carbon-carbon double bonds (saturated vs. unsaturated) and chain length.

Fatty acids with no double bonds between carbon atoms in the hydrocarbon chain.

Fatty acids with one or more double bonds between carbon atoms in the hydrocarbon chain.

Unsaturated fatty acids that humans cannot synthesize and must obtain from the diet (like linoleic and linolenic acids).

Lipid molecules derived from arachidonic acid, acting as hormones affecting smooth muscle contraction. Examples are prostaglandins and leukotrienes.

Eicosanoids that trigger smooth muscle contraction, influencing processes in the gastrointestinal tract.

Fatty acids are carboxylic acids with a long hydrocarbon chain. The general structure is CH3(CH2)nCOOH. The number of carbons (n) is almost always even.

Lipids composed of glycerol backbone with one, two, or three fatty acid chains attached. They are classified as monoglycerides, diglycerides, and triglycerides.

Important components of cell membranes, consisting of a glycerol backbone, two fatty acid chains, and a polar head group attached to the glycerol backbone.

Lipids featuring a sphingosine backbone with varying hydrophilic attachments, resulting in ceramides, sphingomyelins, and glycosphingolipids.

Type of sphingolipid acting as the myelin sheath in the central nervous system, enhancing nerve impulse conduction.

Sphingolipids with sugar attachments, acting as antigens on cell surfaces, crucial for blood type determination.

A type of sterol found in cell membranes, contributing to membrane fluidity and serving as a precursor for various hormones.

Complex molecules with a lipidic portion and a proteinic portion (amino acids), responsible for transporting lipids in the body.

The breakdown of dietary lipids (glycerolipids, glycerophospholipids, and sterides) in the small intestine, preceded by emulsification.

The process of breaking down large fat globules into smaller droplets, coated with bile salts, to increase their surface area for digestion.

Substances produced by the liver, stored in the gallbladder, and released into the small intestine to facilitate emulsification of fats.

The breakdown of triglycerides into glycerol and fatty acids by the enzyme lipase in the small intestine.

Enzymes responsible for breaking down phospholipid molecules into fatty acids, glycerol, and other components.

An enzyme that breaks down cholesterol esters into cholesterol and fatty acids.

A process that breaks down fatty acids into acetyl-CoA molecules in mitochondria, generating energy (ATP).

The process of converting excess carbohydrates and proteins into fatty acids and storing them as triglycerides in adipose tissue.

The formation of ketone bodies in the liver from fatty acids when glucose is scarce.

1. Dehydrogenation: Removes two hydrogen atoms from the fatty acid, forming a double bond.
2. Hydration: Adds a molecule of water to the double bond.
3. Dehydrogenation: Removes another pair of hydrogen atoms, forming a ketone group.
4. Thiolysis: Breaks the bond between the α and β carbons, releasing acetyl-CoA.

Acetyl-CoA is the main product of β-oxidation. It can then enter the Krebs Cycle for further energy production (ATP). It can also be used to synthesize other molecules like fatty acids, ketone bodies, cholesterol, or even proteins and carbohydrates.

β-oxidation generates reducing equivalents (NADH2 and FADH2). These are then used by the ETC to generate ATP, the main energy currency of cells.

Fatty acids with an odd number of carbons undergo similar β-oxidation steps, but the last round produces propionyl-CoA instead of two acetyl-CoA molecules.

Propionyl-CoA is converted to succinyl-CoA, which is an important intermediate in the Krebs cycle. This conversion involves a series of reactions requiring vitamin B12.

The number of ATP molecules produced from β-oxidation can be calculated by considering the number of acetyl-CoA produced and the number of rounds of β-oxidation. For example, stearic acid (C18) produces 148 ATP molecules

β-oxidation is crucial for energy production from fat breakdown, contributing to diverse metabolic processes like the Krebs Cycle, lipogenesis, ketogenesis and even cholesterol biosynthesis.

Propionyl-CoA, a byproduct of odd-numbered fatty acid oxidation, is converted to succinyl-CoA via a three-step process. This involves methylmalonyl-CoA epimerase, a key enzyme for rearranging the molecule, and vitamin B12 as a crucial cofactor. Succinyl-CoA can then enter the Krebs cycle.

Odd-numbered fatty acids undergo -oxidation, producing acetyl-CoA units and one final molecule of propionyl-CoA. This propionyl-CoA is then converted to succinyl-CoA and enters the Krebs cycle.

Branched fatty acids, with methyl groups attached to the carbon chain, are oxidized similarly to unbranched ones. However, the round of -oxidation on the branching carbons yields propionyl-CoA instead of acetyl-CoA. This propionyl-CoA is then converted to succinyl-CoA and enters the Krebs cycle.

Unsaturated fatty acids contain double bonds that require specific enzymes for their oxidation. The process is similar to that of saturated fatty acids, but enzymes like enoyl-CoA isomerase and 2,4-dienoyl-CoA reductase are involved to handle those double bonds.

Propionyl-CoA, a byproduct of odd-numbered and branched fatty acid oxidation, undergoes a multi-step process to be converted to succinyl-CoA. This involves several enzymes and cofactors, including vitamin B12. The resulting succinyl-CoA then enters the Krebs cycle for energy production.

Odd-numbered fatty acids undergo -oxidation, producing acetyl-CoA units and one final molecule of propionyl-CoA. The propionyl-CoA is then converted to succinyl-CoA and enters the Krebs cycle.

Vitamin B12 is a crucial cofactor in the conversion of propionyl-CoA to succinyl-CoA, a step in the oxidation of odd-numbered fatty acids. It is essential for methylmalonyl-CoA mutase, an enzyme involved in this process.

Branched chain fatty acids undergo -oxidation similarly to unbranched fatty acids. However, the round of -oxidation on the branching carbons yields propionyl-CoA instead of acetyl-CoA. This propionyl-CoA is then converted to succinyl-CoA and enters the Krebs cycle.

The double bond in unsaturated fatty acids might need re-positioning (isomerization) to occur between the alpha and beta carbon atoms for β-oxidation to proceed.

When β-oxidation occurs at a double bond, the first step involving FAD (producing FADH2) is skipped.

The total ATP yield from an unsaturated fatty acid is slightly lower than that of a saturated fatty acid with the same number of carbons.

Fatty acids with an odd number of carbon atoms produce propionyl-CoA instead of two acetyl-CoA molecules in the final step of β-oxidation.

In fatty acids with methyl groups, additional propionyl-CoA molecules will be formed during β-oxidation.

To calculate the ATP yield for unsaturated or odd-numbered fatty acids, consider the number of full rounds of β-oxidation, the reduced ATP generated in incomplete rounds, and the ATP produced from propionyl-CoA conversion.