12.4 Lipid Metabolism and Lipoproteins

Lipid metabolism is a complex network of pathways that break down and build up fats in our bodies. From fatty acid synthesis to cholesterol production, these processes are tightly regulated by enzymes and hormones to maintain energy balance and cellular function.

Lipoproteins play a crucial role in transporting lipids through our bloodstream. Understanding their structure and function is key to grasping how lipid disorders can lead to cardiovascular issues. Knowing these basics helps us see why managing cholesterol levels is so important for heart health.

Lipid Metabolism Pathways and Regulation

Pathways of lipid metabolism

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• Fatty acid synthesis occurs in cytoplasm utilizing acetyl-CoA as primary substrate involving fatty acid synthase enzyme
• Fatty acid degradation (β-oxidation) takes place in mitochondria breaking down fatty acids into acetyl-CoA units (ATP production)
• Ketogenesis occurs in liver during fasting or low-carbohydrate diets producing ketone bodies from acetyl-CoA (energy source)
• Cholesterol synthesis begins with acetyl-CoA involving rate-limiting enzyme HMG-CoA reductase (mevalonate pathway)
• Triacylglycerol synthesis combines fatty acids with glycerol occurring in endoplasmic reticulum (energy storage)
• Phospholipid synthesis utilizes fatty acids and polar head groups essential for cell membrane formation (bilayer structure)

Regulation of lipid metabolism

• Key enzymes in lipid metabolism
  • Acetyl-CoA carboxylase regulates fatty acid synthesis (carboxylation of acetyl-CoA)
  • Hormone-sensitive lipase controls lipolysis in adipose tissue (triglyceride breakdown)
  • Lipoprotein lipase hydrolyzes triglycerides in lipoproteins (fatty acid uptake)
• Hormonal regulation
  • Insulin promotes lipogenesis and inhibits lipolysis increasing activity of lipoprotein lipase (fed state)
  • Glucagon stimulates lipolysis and fatty acid oxidation inhibiting fatty acid synthesis (fasting state)
  • Epinephrine and norepinephrine activate hormone-sensitive lipase enhancing lipolysis in adipose tissue (stress response)
• Transcription factors
  • Sterol regulatory element-binding proteins regulate genes involved in cholesterol and fatty acid synthesis (lipid homeostasis)
  • Peroxisome proliferator-activated receptors modulate fatty acid oxidation and storage (lipid metabolism and inflammation)

Lipoproteins and Metabolic Disorders

Structure and function of lipoproteins

• Lipoprotein structure
  • Hydrophobic core contains triglycerides and cholesterol esters (lipid transport)
  • Hydrophilic surface composed of phospholipids, free cholesterol, and apolipoproteins (stability and recognition)
• Lipoprotein functions
  • Transport lipids in bloodstream (solubilization of hydrophobic molecules)
  • Deliver cholesterol and triglycerides to tissues (cellular uptake and metabolism)
• Classification of lipoproteins
  • Chylomicrons largest and least dense transport dietary lipids from intestines to tissues (exogenous pathway)
  • Very low-density lipoproteins synthesized in liver transport endogenous triglycerides (endogenous pathway)
  • Low-density lipoproteins derived from VLDL primary carrier of cholesterol to tissues (cholesterol delivery)
  • High-density lipoproteins smallest and most dense involved in reverse cholesterol transport (atheroprotective)

Lipid disorders and cardiovascular health

• Dyslipidemia abnormal levels of lipids in blood risk factor for atherosclerosis and cardiovascular disease (LDL-C, HDL-C, TG)
• Familial hypercholesterolemia genetic disorder causing elevated LDL cholesterol levels increased risk of premature cardiovascular events (LDL receptor mutations)
• Metabolic syndrome cluster of conditions including dyslipidemia and insulin resistance associated with increased risk of heart disease and type 2 diabetes (central obesity)
• Atherosclerosis accumulation of lipids and inflammatory cells in artery walls can lead to coronary artery disease and stroke (plaque formation)
• Therapeutic approaches
  1. Statins inhibit HMG-CoA reductase to lower cholesterol synthesis
  2. Fibrates activate PPARs to reduce triglycerides and increase HDL
  3. PCSK9 inhibitors enhance LDL receptor activity to lower LDL cholesterol
• Lifestyle interventions
  • Dietary modifications reducing saturated fat and increasing omega-3 fatty acids (Mediterranean diet)
  • Regular physical activity improves lipid profile and cardiovascular health (aerobic exercise)