Lipids: Structure and Clinical Relevance

Lipids: Structure, Function, and Clinical Relevance

• Lipids are fatty, water-insoluble substances with diverse roles in cells.
• They are crucial components of biological membranes.
• Lipids are used as metabolic fuels, precursor to hormones, and participate in cell signaling.

Classification of Lipids

• Simple Lipids: Hydrolysis yields alcohol and fatty acids (e.g., waxes, triglycerides).
• Compound/Complex Lipids: Hydrolysis yields alcohol, fatty acids, and other components like phosphate groups or sugars (e.g., phospholipids, glycolipids).
• Derived/Polyprenyl Lipids: Non-hydrolysable, derivatives of isoprene (e.g., fat-soluble vitamins A, D, steroids like cholesterol, aldosterone, testosterone, and estrogen).

Cholesterol and Cardiovascular Disease

• High cholesterol contributes to cardiovascular disease (CVD).
• Cholesterol metabolism is linked to fat (triglyceride) metabolism influencing the effect of diet.
• Atheroma formation involves cholesterol-rich deposits in artery walls.
• Lipids are transported as lipoproteins in the blood, their uptake in artery walls leading to atheroma development.
• Key components of a lipid profile include total cholesterol, triglycerides, HDL-C, LDL-C, and non-HDL-C.

Fatty Acids (FAs)

• Structure: Even-numbered carbon chain with a carboxyl group.
• Saturation: Saturated FAs (no double bonds), Unsaturated FAs (one or more double bonds, including polyunsaturated FAs with multiple double bonds).
• Configuration: Naturally occurring FAs are usually cis (hydrogens on the same side of the double bond), whereas trans FAs are typically harmful (hydrogens on opposite sides).

Triacylglycerols (TAGs)

• Structure: Three fatty acid (FA) residues esterified to a glycerol backbone.
• Synthesis: Occurs in adipocytes, utilizing glycerol 3-phosphate from glycolysis, and fatty acid acyl transferases in the smooth endoplasmic reticulum.
• Storage: Stored as lipid droplets within adipocytes, coated with perilipin protein.

TAGs – Energy Storage and Regulation

• TAGs are the major energy reserve in adipocytes.
• Lipolysis (breakdown of TAGs) is regulated by hormone-sensitive lipase (HSL). Insulin inhibits lipolysis by preventing HSL action; fasting hormones (catecholamines, glucagon, growth hormone) stimulate it.

Phospholipids (PLs) and Cholesterol

• Structure: Similar to TAGs, but with a phosphate ester at the Sn3 position (e.g., phosphatidylcholine).

• Function: Major components in biological membranes (40-50% of membrane lipids)

• Cholesterol: A sterol with a hydroxyl group at C-3; can be esterified to form cholesterol ester.

• Functions: Precursor of steroid hormones, vitamins D, bile acids; crucial component of biological membranes.

Cholesterol Biosynthesis and Absorption

• Biosynthesis: Involves the reduction of HMG-CoA to mevalonate. HMG-CoA reductase is a key regulatory enzyme (target of statins).
• Absorption: Dietary cholesterol is solubilized by bile salts and fats to form mixed micelles in the duodenum and jejunum. Cholesterol esters are hydrolyzed into free cholesterol, then absorbed via NPC1L1. Plant sterols are returned to the gut lumen, with cholesterol being transported as CEs in chylomicrons.

This quiz explores the structure, function, and clinical importance of lipids, focusing on their roles in biological membranes and metabolic processes. It also covers the classification of lipids and their connection to cardiovascular disease, particularly cholesterol's impact on health.