Sterols: Structures and Functions

Sterols: Structures and Biological Functions

• Steroids are complex molecules with 4 fused rings.
• Often found in association with fats, but separable after saponification.
• All steroids share a similar cyclic nucleus resembling phenanthrene (rings A, B, and C), with a cyclopentane ring (ring D) attached.
• This structure is called cyclopentanoperhydrophenanthrene, or sterane/gonane ring.
• Sterols are steroid alcohols, where a hydroxyl group replaces a hydrogen atom at position 3.
• Methyl side chains typically occur at positions 10 and 13 (carbons 19 and 18, respectively), plus a side chain at position 17.
• Sterols are amphipathic lipids synthesized from acetyl coenzyme A through the HMG-CoA reductase pathway.
• Found in eukaryotes (plants, animals, fungi).
• Plant sterols are called phytosterols; animal sterols are zoosterols.
• Cholesterol is the most important zoosterol.
• Notable phytosterols include campesterol, sitosterol, and stigmasterol.
• Sterols play crucial roles in eukaryotic physiology.
• Cholesterol is a significant component of animal cell membranes, affecting fluidity and acting as a secondary messenger in developmental signaling.
• Corticosteroids (e.g., cortisol) act as signaling compounds in humans.
• Sterols are components of human skin oils.
• Phytosterols reduce cholesterol absorption in the human intestine, as shown in clinical trials.
• The American Heart Association recommends supplemental plant sterols for hypercholesterolemia (but not for pregnant or nursing women).
• Some phytosterols show preliminary anti-cancer effects.

Cholesterol

• The most important sterol in humans, with molecular formula C₂₇H₄₅OH.
• Biosynthesized by all animal cells and is an essential structural component of animal cell membranes.
• Possesses a cyclopentanoperhydrophenanthrene nucleus.
• Contains an –OH group at C3.
• Has an unsaturated double bond between C5 and C6.
• Has two –CH₃ groups at C10 and C13.
• An eight-carbon side chain is attached to C17.
• The name "cholesterol" stems from the Greek word for "solid bile."
• Occurs as a white or faintly yellow, almost odorless, granular solid.
• Insoluble in water but sparingly soluble in alcohol and soluble in ether, chloroform, hot alcohol, ethyl acetate and vegetable oils.
• No saponification occurs.
• Melting point is 147–150 °C.
• Can take up two halogen atoms due to an unsaturated bond.

Cholesterol Sources

• Exogenous: Dietary cholesterol (approximately 0.3 g/day) from foods rich in cholesterol (butter, cream, milk, egg yolks, meat, etc.). A hen's egg (2 oz) provides ~250 mg of cholesterol.
• Endogenous: Synthesized in the body from acetyl CoA (approximately 1 g/day).
• High concentrations in brain/nervous tissue (2% ), liver (0.3%), skin (0.3%), intestinal mucosa (0.2%).
• Also present in endocrine glands (e.g. adrenal cortex, up to 10%) and corpus luteum.

Cholesterol Forms

• Cholesterol exists in free and ester forms.
• Esterified with fatty acids at the –OH group at position C3.
• Ester forms are also referred to as "bound" forms.
• The various fatty acids making up cholesterol esters include linoleic acid (50%), oleic acid (18%), palmitic acid (11%), arachidonic acid (5%), and other fatty acids (16%).
• Most plasma cholesterol esters are produced in the plasma itself by the transfer of an acyl group (mostly unsaturated) from the β-position of lecithin to cholesterol, aided by the enzyme lecithin-cholesterol acyltransferase (LCAT).

Norum's Disease

• A genetic deficiency of LCAT.
• Results in the failure of cholesterol esterification, impacting lecithin.
• Characterized by increased free cholesterol and lecithin in plasma, and reduced cholesterol esters and lysolecithin.

Normal Cholesterol Levels

• Serum total cholesterol levels in adults typically vary between 150 and 250 mg/dL.
• About 40-50 mg% is free cholesterol.
• 110-200 mg% is in cholesterol ester form.
• Cholesterol levels vary with age, sex (slightly higher in women before and a little lower after menstruation), and pregnancy (increased during pregnancy).

Other Sterols

• 7-Dehydrocholesterol: An important sterol in skin, differing from cholesterol by a second double bond between C₇ and C₈.
  • A precursor to vitamin D3. UV radiation converts 7-dehydrocholesterol to vitamin D3 (cholecalciferol), which is crucial for preventing rickets.
• Ergosterol: A plant sterol, precursor to vitamin D2. UV irradiation converts ergosterol to vitamin D2. Over-irradiation can cause toxic products
• Stigmasterol and Sitosterol: Plant sterols with no nutritional value for humans. They reduce intestinal absorption of cholesterol.
• Coprosterol: Formed from cholesterol in the gut by bacterial action, where the C5-C6 double bond is saturated.
• Other important steroids include bile acids, adrenocortical hormones, gonadal hormones, D vitamins, cardiac glycosides, and some alkaloids.