What is the distribution of cholesterol between tissues and lipoproteins in the body?

Distribution of Cholesterol Between Tissues and Lipoproteins in the Body

The majority of cholesterol in the human body (approximately 80%) is found in tissues, with only about 20% circulating in lipoproteins in the bloodstream. 1

Tissue Cholesterol Distribution

• Cholesterol is an essential component of cell membranes throughout the body, providing structural integrity and regulating membrane fluidity 2
• The central nervous system contains approximately 23% of total body cholesterol in humans (15% in mice) 3
• Brain cholesterol is synthesized locally as cholesterol cannot cross the blood-brain barrier, even in newborns 3
• Cholesterol in tissues serves as a precursor for:
  • Bile acids
  • Steroid hormones
  • Vitamin D
  • Other essential metabolites 2

Lipoprotein Cholesterol Distribution

Circulating cholesterol is transported in various lipoprotein particles:

• LDL (Low-Density Lipoprotein): Contains the majority of circulating cholesterol in normal human plasma 4

  • Primary function is to distribute cholesterol to peripheral tissues
  • Binds to specific LDL receptors on cell surfaces

• HDL (High-Density Lipoprotein):

  • Facilitates reverse cholesterol transport from peripheral tissues to the liver
  • Plays a crucial role in withdrawing cholesterol from circulation 1

• VLDL (Very Low-Density Lipoprotein):

  • Primarily carries triglycerides but also contains cholesterol
  • Assembled in the liver's endoplasmic reticulum 5

• IDL (Intermediate-Density Lipoprotein):

  • Formed during the metabolism of VLDL
  • Some IDL particles are removed by the liver while others are converted to LDL 5

• Chylomicrons:

  • Transport dietary cholesterol from the intestine
  • After absorption as free cholesterol, much is re-esterified within enterocytes by ACAT2, then packaged into chylomicrons 1

Cholesterol Metabolism and Regulation

• The human body maintains a stable cholesterol pool through:

  • De novo synthesis (approximately 1g/day)
  • Dietary intake (varies with diet)
  • Intestinal absorption (>50% of dietary cholesterol) 1, 6

• Cholesterol is excreted from the body through:

  • Conversion to bile acids in the liver
  • Direct secretion into bile
  • From the brain, as 24(S)-hydroxycholesterol 3

Clinical Implications

• Disruptions in cholesterol distribution and metabolism can lead to:

  • Cardiovascular disease (when excess cholesterol accumulates in arterial walls)
  • Neurological disorders (when brain cholesterol metabolism is disrupted)
  • Metabolic disorders (when cholesterol synthesis or transport is impaired) 2

• Measuring circulating cholesterol provides only a partial picture of total body cholesterol status, as it represents only about 20% of total body cholesterol 1

Understanding this distribution is crucial for interpreting lipid profiles and developing strategies to manage cholesterol-related disorders that impact mortality and quality of life.