Exam Review

Lipid Metabolism and Dietary Implications

Overview of Lipid Storage and Membrane Composition

• Plasma Membrane: Composed mainly of lipids, which are critical for cellular functions and storing energy.

• Adipose Tissue: Stores lipids that can be recruited for various physiological reasons. These lipids in the lipid bilayer primarily function as signaling molecules.

Diet Selection and Physiological Regulation

• Importance of Diet in Lipid Metabolism:

  • Lipid types are influenced by dietary selection, considering both quantity and quality.

  • Carbohydrates can be classified into simple and complex carbs, but diet plays a more significant role in regulating physiological responses.

  • Preference for anti-inflammatory signaling molecules over inflammatory ones, suggesting dietary choices can influence inflammatory responses significantly.

Lipoproteins and Their Role in Lipid Transport

• Lipoprotein Overview:

  • Chylomicrons: Originates from intestines (enterocytes); main cargo includes.

  • Triglycerides from dietary sources, often visualized descriptively as a "beach ball" due to their size and function.

  • Chylomicrons enter circulation via the lymphatic system.

  • Functionality of HDL (High-Density Lipoprotein):

  • Helps clear triglyceride-rich chylomicrons by providing apoprotein C-II, a key that activates lipoprotein lipase (LPL).

  • Without sufficient HDL, chylomicrons remain in circulation longer.

Interplay of Different Lipoproteins

• VLDL (Very Low-Density Lipoprotein):

  • Produced by liver cells (hepatocytes) with the main apoprotein B-100.

  • Carries triglycerides synthesized from excess carbohydrates through the process known as de novo lipogenesis.

  • VLDL transitions to LDL (Low-Density Lipoprotein) as it delivers triglycerides and loses density.

  • Impacts of hormonal states on VLDL: Insulin and its regulation of LPL can alter the delivery of triglycerides to tissues.

Cholesterol and Cellular Uptake Processes

• LDL (Low-Density Lipoprotein):

  • Primary function in transporting cholesterol to tissues.

  • Cells possess LDL receptors that bind to B-100 on LDL particles to uptake cholesterol as needed.

  • Uptake triggers a decrease in the synthesis of cholesterol in cells, leading to reduced LDL receptor expression.

  • Implications of carbohydrate intake: High carbohydrate diets can elevate circulating LDL levels by inhibiting its cellular uptake.

Metabolic Pathways of Lipid Breakdown and Synthesis

• Breakdown of Triglycerides:

  • Triggered by hormonal signals; glucagon stimulates lipolysis in adipose tissue leading to fatty acid release.

  • Enzymatic breakdown involves:

  • Adipose Triglyceride Lipase (ATGL): Converts triglycerides (TAGs) to diacylglycerols (DAGs).

  • Hormone-Sensitive Lipase: Transforms DAGs to monoacylglycerols (MAGs).

  • Monoglyceride Lipase: Further breaks down MAGs into free fatty acids and glycerol.

• Fate of Released Fatty Acids:

  • Transported in blood bound to albumin or as free fatty acids to various tissues for energy use.

Fatty Acid Metabolism in Tissues

• Entry into Mitochondria:

  • Fatty acids are converted to fatty acyl-CoA by attaching Coenzyme A for mitochondrial transport.

  • Catalyzed by CPT1 (Carnitine Palmitoyltransferase I) to facilitate mitochondrial entry.

• Beta Oxidation:

  • Process where fatty acids are cleaved into Acetyl-CoA, necessary for ATP production.

  • Energy state influences this process; high ATP levels inhibit and low ATP levels promote beta oxidation.

  • Regulated by malonyl-CoA; a product of lipogenesis, inhibiting CPT1 during fed states to prevent breakdown of fatty acids when energy is sufficient.

Hormonal Regulation

• Insulin vs. Glucagon:

  • Insulin promotes lipogenesis, stimulating enzymes necessary for fatty acid synthesis and storage (e.g., Acetyl-CoA carboxylase).

  • Glucagon encourages lipolysis, enhancing the breakdown of stored fats to meet energy demands.

• Key Enzymes in Lipogenesis:

  • Citrate Lyase:

  • Converts citrate back to Acetyl-CoA in the cytosol, initiating fatty acid synthesis when in excess.

  • Malic Enzyme: Participates in generating NADPH for fatty acid synthesis.

Practical Implications for Health

• Importance of understanding lipid metabolism in relation to dietary choices and diseases such as cardiovascular disease.

• Insulin's role not just in glucose control but also influencing lipid metabolism and transport mechanisms contributes to understanding metabolic disorders.

• Future Considerations:

  • Need for repeated exposure to these metabolic pathways for mastery, with practical applications in understanding health impacts from diet.

  • Official examinations may include questions on fatty acid nomenclature, pathways, and potential metabolic disruptions from dietary imbalances.

Summary of Key Terms & Concepts

• Chylomicron: A lipoprotein transporting dietary triglycerides.

• VLDL: Very low-density lipoproteins, carry triglycerides from the liver.

• LDL: Low-density lipoproteins, primary carriers of cholesterol to tissues.

• HDL: High-density lipoproteins, involved in removing cholesterol from circulation.

• Beta-oxidation: The oxidative breakdown of fatty acids into Acetyl-CoA.

• Malonyl-CoA: Inhibitory molecule in fatty acid oxidation during lipogenesis.

• Apoproteins: Proteins that bind lipids, which are essential for lipoprotein functionality and cellular interactions.