Introduction to Lipids

Lipid Overview

• Lipids are hydrophobic or amphiphilic molecules, soluble in nonpolar solvents and generally insoluble in water.
• Essential functions include energy storage, cell membrane structure, and signaling.

Types of Lipids

• Triglycerides (Triacylglycerols):

  • Composed of glycerol and three fatty acids; primary energy storage in animals and plants; stored in adipose tissue.

• Phospholipids:

  • Structure includes glycerol, two fatty acids, and a phosphate group; critical components of cell membranes, contributing to membrane fluidity and barrier function.

• Steroids:

  • Composed of four fused carbon rings; includes cholesterol, vital for steroid hormone production (e.g., estrogen, testosterone) and membrane stabilization.

• Glycolipids:

  • Consist of glycerol, fatty acids, and carbohydrates; involved in cell recognition and communication within membranes.

• Waxes:

  • Made of long-chain fatty acids and alcohols; serve as protective barriers in plants and animals (e.g., plant cuticles, earwax).

• Sphingolipids:

  • Built on a sphingosine backbone with one fatty acid; significant in signaling and cell recognition, particularly in nerve and immune cells.

Functions of Lipids

• Energy Storage: Primarily served by triglycerides in adipose tissue.
• Structural Components: Phospholipids and cholesterol are fundamental to cell membrane architecture.
• Signaling Molecules: Lipids such as steroid hormones regulate physiological functions.
• Insulation and Protection: Lipids provide cushioning for organs and thermal insulation.

Dietary Lipids

• Include triglycerides, phospholipids, and cholesterol, crucial for energy, structure, and hormone synthesis.

Lipid Digestion and Absorption

• Digestion:

  • Begins in the mouth with lingual lipase; gastric lipase continues in the stomach; pancreatic lipase acts in the small intestine with bile salts to hydrolyze triglycerides into monoglycerides and free fatty acids.

• Absorption:

  • Digested lipids form micelles for absorption by intestinal mucosa; monoglycerides and fatty acids are reassembled into triglycerides and packaged into chylomicrons for transport.

Lipid Transport and Metabolism

• Chylomicrons: Transport dietary lipids from intestines to tissues; hydrolyzed by lipoprotein lipase (LPL) for energy or storage.

• VLDL: Transports endogenous triglycerides from the liver to tissues; also processed by LPL.

• IDL: Intermediate form of VLDL; converts to LDL or taken up by the liver.

• LDL: Carries cholesterol to tissues, often termed "bad cholesterol" due to atherosclerosis risk.

• HDL: Collects excess cholesterol from tissues, transporting it back to the liver; known as "good cholesterol" for reducing cardiovascular risk.

Fatty Acid Metabolism

• Synthesis:

  • Occurs mainly in liver and adipose tissues; initiated by acetyl-CoA through the acetyl-CoA carboxylase (ACC) enzyme.

• β-Oxidation:

  • Takes place in mitochondria; fatty acids are activated to fatty acyl-CoA and broken down into acetyl-CoA, NADH, and FADH2.

Triacylglycerol Metabolism

• Synthesis: Involves glycerol-3-phosphate from glucose or glycerol; fatty acids are esterified to form triacylglycerols, catalyzed by diacylglycerol acyltransferase (DGAT).

Steroid Hormone Synthesis

• Location: Primarily in adrenal glands and gonads.
• Process: Cholesterol converts to pregnenolone and then to various steroid hormones, including glucocorticoids (e.g., cortisol) and sex steroids (e.g., estrogen).

Clinical Relevance

• Dyslipidemia: Elevated LDL, low HDL levels linked to increased cardiovascular disease risk.
• Obesity: Excess triglyceride accumulation in adipose tissue, a key factor in metabolic syndrome and type 2 diabetes.
• Fatty Liver Disease: Lipid accumulation in liver can lead to NAFLD or alcoholic liver disease.

Integration with Other Metabolic Pathways

• Lipid metabolism interacts with carbohydrate and protein metabolism, maintaining energy balance during fasting and feeding.
• Hormonal influences include insulin for lipogenesis and glucagon/epinephrine for lipolysis.

Cholesterol and Lipoprotein Disorders

• Hypercholesterolemia: Elevated cholesterol levels increasing cardiovascular risk; managed through lifestyle and statin medications.

• Familial Hypercholesterolemia: Genetic disorder causing high LDL, early atherosclerosis development.

Steroid Disorders

• Adrenal Insufficiency: Low adrenal steroid production, leading to fatigue and weight loss.
• Cushing’s Syndrome: Excess cortisol; symptoms include obesity, hypertension, diabetes.