Digestion and absorption of lipids

Mr. Arvind Kumar

Digestion and absorption of lipids processes for “triglycerides, cholesterol, and phospholipids”, including specific enzymes, mechanisms, and physiological implications.

Digestion of Triglycerides (TGs)

  1. Mouth:

    • Lingual Lipase:
      • Produced by: Serous glands of the tongue.
      • Function: Begins the digestion of triglycerides, converting them into diglycerides and free fatty acids. Although the action is minor, it sets the stage for more extensive digestion in the stomach.

  1. Stomach:

    • Gastric Lipase:
      • Produced by: Chief cells in gastric mucosa.
      • Function: Further hydrolyzes triglycerides into diglycerides and free fatty acids. Gastric lipase operates optimally at a low pH (around 3-6) and is particularly effective on medium-chain triglycerides.
    • Mechanical Mixing:
      • Churning of the stomach also helps emulsify fats, breaking them into smaller droplets, which increases the surface area for enzymatic action.

  1. Small Intestine:

    • Bile Salts:
      • Produced by: Liver, stored in the gallbladder.
      • Function: Upon release into the duodenum, bile salts emulsify large fat globules into smaller micelles. This process is crucial because it allows pancreatic lipase access to triglycerides.
    • Pancreatic Lipase:
      • Produced by: Pancreas.
      • Function: Hydrolyzes triglycerides into monoglycerides and two free fatty acids. This enzyme is highly efficient and requires the presence of bile salts for optimal activity.
    • Colipase:
      • Produced by the pancreas (as a proenzyme, activated in the intestine).
      • Function: Binds to the lipid-water interface, displacing bile salts and anchoring pancreatic lipase, enhancing its ability to digest triglycerides.

  1. Absorption:

    • Formation of Micelles:
      • Digestion products (monoglycerides and free fatty acids) aggregate with bile salts to form micelles, transporting lipids to the enterocytes’ brush border.
    • Transport into Enterocytes:
      • Mechanisms:
        • Passive Diffusion: Monoglycerides and free fatty acids enter enterocytes by simple diffusion due to their lipophilic nature.
        • Transport Proteins: Some fatty acids may also be transported via specific fatty acid transport proteins (FAT/CD36).
      • Inside Enterocytes:
        • Re-esterification: Once inside, monoglycerides and free fatty acids are re-esterified into triglycerides in the smooth endoplasmic reticulum.
        • Packaging into Chylomicrons: Triglycerides, along with cholesterol and phospholipids, are packaged into chylomicrons, which are large lipoprotein particles.

Digestion of Cholesterol

  1. Small Intestine:

    • Cholesterol Esterase:
      • Produced by: Pancreas.
      • Function: Hydrolyzes cholesterol esters into free fatty acids, making cholesterol available for absorption.
    • Bile Salts:
      • Aid in emulsifying dietary cholesterol, improving its solubility and absorption.

  1. Absorption:

    • Mechanism:
      • Free cholesterol is absorbed primarily via the Niemann-Pick C1-like 1 (NPC1L1) transporter, facilitating its uptake into enterocytes.
      • Some cholesterol is also absorbed through passive diffusion.
    • Inside Enterocytes:
      • Re-esterification: Free cholesterol can be re-esterified into cholesterol esters for storage or incorporation into chylomicrons.

Digestion of Phospholipids

  1. Small Intestine:

    • Phospholipase A2:
      • Produced by: Pancreas.
      • Function: Hydrolyzes phospholipids (e.g., lecithin) into lysophospholipids and free fatty acids. This step is crucial for releasing fatty acids from phospholipid molecules.

  1. Absorption:

    • Mechanism:
      • Lysophospholipids can be absorbed via passive diffusion or specific transporters, similar to free fatty acids.
    • Inside Enterocytes:
      • Lysophospholipids can be reassembled into phospholipids or incorporated into chylomicrons.

Mechanism of lipid absorption

The mechanism of lipid absorption involves several steps and processes that enable the efficient uptake of dietary lipids in the intestine. Here’s a detailed look at how this occurs:

  1. Emulsification

  • Bile Salts:
    • Secreted from the gallbladder into the small intestine, bile salts emulsify dietary fats. They reduce the surface tension of fat globules, breaking them into smaller droplets, which increases the surface area for enzyme action.
  • Micelle Formation:
    • After emulsification, bile salts, free fatty acids, monoglycerides, and other lipid digestion products form micelles. Micelles are aggregates of lipids surrounded by bile salts that transport lipids to the intestinal brush border.

  1. Transport to the Brush Border

  • Micelle Action:
    • Micelles move through the intestinal lumen and deliver their lipid contents to the brush border of enterocytes (intestinal absorptive cells). The lipids diffuse from the micelles across the cell membrane due to their lipid solubility.

  1. Absorption into Enterocytes

  • Diffusion Mechanism:
    • Passive Diffusion: Monoglycerides and free fatty acids can easily diffuse across the lipid bilayer of the enterocyte membrane due to their hydrophobic nature.
  • Transport Proteins:
    • Some fatty acids, particularly short- and medium-chain, may use specific transport proteins such as FAT/CD36 and FATP (fatty acid transport proteins) to facilitate absorption.

  1. Intracellular Processing

  • Re-esterification:
    • Once inside the enterocyte, monoglycerides and free fatty acids are re-esterified into triglycerides in the smooth endoplasmic reticulum.
    • Short- and medium-chain fatty acids may enter the bloodstream directly, while long-chain fatty acids are packaged into lipoproteins.
  • Chylomicron Formation:
    • Newly synthesized triglycerides, cholesterol, and phospholipids are assembled into chylomicrons, lipoprotein particles that transport dietary lipids.
    • Apolipoproteins (such as ApoB-48) are added to chylomicrons during this process, essential for their structure and function.

  1. Exocytosis of Chylomicrons

  • Release into the Lymphatic System:
    • Chylomicrons are released from enterocytes via exocytosis into the interstitial fluid and enter the lymphatic system through lymphatic capillaries (lacteals).
  • Transport to Bloodstream:
    • Chylomicrons travel through the lymphatic system and eventually reach the bloodstream via the thoracic duct. This allows the transport of dietary lipids to various tissues in the body.

  1. Lipid Utilization

  • Lipoprotein Lipase (LPL):
    • Located on the endothelial surface of capillaries, LPL hydrolyzes triglycerides in chylomicrons into free fatty acids and glycerol.
    • These free fatty acids can then be taken up by surrounding tissues (e.g., muscle for energy or adipose tissue for storage).

Disorders

Abnormalities in lipid digestion and absorption can lead to various health issues. Here are some common conditions and their underlying mechanisms:

  1. Malabsorption Syndromes

These conditions hinder the body’s ability to absorb lipids effectively.

  • Celiac Disease:
    • Mechanism: An autoimmune disorder that damages the small intestine’s lining in response to gluten, impairing nutrient absorption, including lipids.
    • Symptoms: Diarrhea, weight loss, bloating, and nutrient deficiencies.
  • Chronic Pancreatitis:
    • Mechanism: Inflammation of the pancreas reduces the secretion of digestive enzymes, including pancreatic lipase, leading to poor digestion of fats.
    • Symptoms: Steatorrhea (fatty stools), abdominal pain, weight loss, and nutrient deficiencies.
  • Short Bowel Syndrome:
    • Mechanism: A condition resulting from surgical removal of part of the small intestine, leading to reduced absorption surface area.
    • Symptoms: Diarrhea, dehydration, and malnutrition due to inadequate absorption.

  1. Lipid Metabolism Disorders

These genetic disorders affect lipid processing and transport.

  • Familial Hypercholesterolemia:
    • Mechanism: Genetic mutations affect the LDL receptor, leading to elevated levels of low-density lipoprotein (LDL) cholesterol in the blood.
    • Symptoms: Early onset cardiovascular disease and cholesterol deposits (xanthomas).
  • Lipid Storage Diseases:
    • Examples: Tay-Sachs disease and Gaucher’s disease.
    • Mechanism: Enzyme deficiencies lead to the accumulation of lipids in tissues.
    • Symptoms: Vary widely but can include neurological symptoms and organomegaly.

  1. Bile Acid Deficiency

Bile acids are essential for lipid emulsification and absorption.

  • Biliary Atresia:
    • Mechanism: A congenital condition where bile ducts are absent or damaged, preventing bile from reaching the intestine.
    • Symptoms: Jaundice, poor weight gain, and fat malabsorption.
  • Cholecystectomy:
    • Mechanism: Surgical removal of the gallbladder can lead to reduced bile storage, affecting lipid digestion, especially after high-fat meals.
    • Symptoms: Diarrhea and steatorrhea.

  1. Intestinal Disorders

Conditions that affect the integrity of the intestinal lining can impair absorption.

  • Irritable Bowel Syndrome (IBS):
    • Mechanism: A functional gastrointestinal disorder that may affect the absorption of nutrients, including lipids, due to altered gut motility.
    • Symptoms: Abdominal pain, bloating, diarrhoea, or constipation.
  • Inflammatory Bowel Disease (IBD):
    • Examples: Crohn’s disease and ulcerative colitis.
    • Mechanism: Inflammation of the gastrointestinal tract leads to compromised absorption.
    • Symptoms: Abdominal pain, diarrhoea, weight loss, and fatigue.

  1. Excessive Fat Intake

High-fat diets can lead to various metabolic issues.

  • Obesity:
    • Mechanism: Excessive caloric intake, especially from fats, leads to increased adiposity and related health complications.
    • Symptoms: Increased risk of diabetes, cardiovascular disease, and metabolic syndrome.
  • Hyperlipidemia:
    • Mechanism: Elevated levels of lipids (triglycerides and cholesterol) in the blood can result from poor dietary habits, genetic factors, or metabolic disorders.
    • Symptoms: Often asymptomatic, but can lead to cardiovascular issues.

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