8.(b) Draw structure of cholesterol and explain its role in health and diseases.

1. Structure of Cholesterol

Cholesterol (C₂₇H₄₆O) is a 27-carbon sterol with a distinctive four-ring steroid nucleus, a hydrocarbon tail, and a hydroxyl group. This amphipathic nature, with a polar hydroxyl group and a non-polar steroid body and hydrocarbon tail, allows it to embed within cell membranes.

Chemical Structure Diagram:

      CH3
      |
    H3C-CH-CH2-CH2-CH2-CH
                |      |
        CH3  CH3  CH3  CH3
        |
    (Ring D)  CH
    /     \ /   \
  CH2--CH---CH---CH2
  |     |     |     |
  CH----CH----CH----CH
  \   / \   / \   / \   /
   CH2   CH   CH2   CH
   |     |     |     |
   CH----CH----CH----CH2
   \   / \   / \   /
    CH2   CH2   CH2
    |
    C
   / \
  CH   OH
  ||
  CH

Key features:

• Steroid Nucleus: Consists of four fused hydrocarbon rings (three six-membered cyclohexanes and one five-membered cyclopentane).
• Hydroxyl Group (-OH): Located at the 3-beta position of the A ring, making it an alcohol (hence '-ol' in cholesterol). This polar group gives cholesterol its amphipathic properties.
• Hydrocarbon Tail: A long, branched chain of eight carbons attached to the D ring at position 17. This is non-polar.
• Methyl Groups: Several methyl groups are attached to the rings.

2. Role in Health

Cholesterol performs numerous essential physiological functions, integral to the normal functioning of animal cells and organisms:

• Component of Cell Membranes: Cholesterol is a crucial structural component of animal cell membranes. It intercalates between phospholipid molecules, regulating membrane fluidity, stability, and permeability. This allows animal cells to maintain integrity without a cell wall and facilitates cell shape changes and movement.
• Precursor for Steroid Hormones: It serves as the primary precursor for the synthesis of all steroid hormones, including:
  • Corticosteroids: Such as cortisol and aldosterone, vital for stress response, immune function, and electrolyte balance.
  • Sex Hormones: Including estrogen, progesterone, and testosterone, which regulate reproductive functions and secondary sexual characteristics.
• Vitamin D Synthesis: In the skin, cholesterol derivatives are converted into Vitamin D upon exposure to ultraviolet B (UVB) radiation. Vitamin D is essential for calcium metabolism, bone health, and immune system regulation.
• Bile Acid Production: In the liver, cholesterol is metabolized to produce bile acids (e.g., cholic acid, chenodeoxycholic acid). These bile acids are critical for the emulsification of dietary fats in the small intestine, facilitating their digestion and absorption, along with fat-soluble vitamins (A, D, E, K).
• Insulation of Nerve Cells: Cholesterol is a major component of myelin, the insulating sheath that surrounds nerve fibers. Myelin is crucial for the efficient and rapid transmission of nerve impulses.
• Cell Signaling: It is involved in the formation of lipid rafts within cell membranes, which are specialized microdomains facilitating cell signaling pathways and receptor interactions.

3. Role in Diseases

While essential, an imbalance in cholesterol levels, particularly high levels of Low-Density Lipoprotein (LDL) cholesterol, is a significant risk factor for various chronic diseases.

3.1. Cardiovascular Diseases (CVDs)

The most prominent link of cholesterol to disease is its role in cardiovascular diseases, especially atherosclerosis.

• Atherosclerosis: High levels of LDL ("bad") cholesterol lead to the accumulation of cholesterol and other substances (fats, blood cells, calcium) in the inner lining of arteries, forming plaque. This condition, called atherosclerosis, causes arteries to narrow and harden, reducing blood flow.
• Coronary Artery Disease (CAD): Plaque buildup in the coronary arteries, which supply blood to the heart, leads to CAD. This can cause angina (chest pain), heart attacks (myocardial infarction) due to blockages, or abnormal heart rhythms.
• Stroke: If plaque ruptures in arteries leading to the brain, or a blood clot formed in a narrowed artery travels to the brain, it can cause an ischemic stroke, interrupting blood flow to parts of the brain.
• Peripheral Artery Disease (PAD): Atherosclerosis in arteries supplying blood to the limbs (most often legs) can lead to PAD, causing pain, numbness, and in severe cases, tissue damage.

3.2. Other Diseases

• Gallstones: An excess of cholesterol in bile can lead to the formation of cholesterol gallstones in the gallbladder, causing pain and digestive issues.
• Pancreatitis: Very high triglyceride levels (often associated with dyslipidemia, which can involve cholesterol imbalance) can lead to acute pancreatitis.
• Type 2 Diabetes: While not a direct cause, dyslipidemia (including high LDL and low HDL) is commonly observed in individuals with Type 2 Diabetes and exacerbates the risk of cardiovascular complications in these patients.
• Familial Hypercholesterolemia (FH): This is a genetic disorder characterized by very high levels of LDL cholesterol from birth, leading to premature and aggressive atherosclerosis and early onset heart disease.

The balance between High-Density Lipoprotein (HDL) and Low-Density Lipoprotein (LDL) is crucial. HDL ("good") cholesterol helps remove excess cholesterol from arteries and transport it back to the liver for excretion, thereby protecting against atherosclerosis. Conversely, high LDL cholesterol actively contributes to plaque formation.

Maintaining healthy cholesterol levels through lifestyle modifications (diet, exercise, cessation of smoking and excessive alcohol consumption) and, if necessary, medication, is paramount in preventing and managing these diseases. Recent Indian guidelines emphasize non-fasting lipid measurements for risk assessment and setting target LDL-C levels, recognizing the high burden of cardiovascular diseases in the country.