Conversion of cholesterol into bile acids, steroid hormone & vitamin D

• The conversion of cholesterol into bile acids, steroid hormones, and vitamin D refers to the biochemical transformation of cholesterol into essential molecules that play critical roles in digestion, endocrine function, and calcium homeostasis.
• These metabolic pathways occur in different tissues and are tightly regulated to maintain physiological balance.

Conversion of Cholesterol into Bile Acids:

Primary Location:

• Liver

Steps Involved:

1. Initial Step:

   • Cholesterol is converted to 7α-hydroxycholesterol by the enzyme cholesterol 7α-hydroxylase (CYP7A1), which is the rate-limiting step in bile acid synthesis.

2. Subsequent Reactions:

   • Further hydroxylation, oxidation, and conjugation reactions lead to the production of cholic acid and chenodeoxycholic acid, the two primary bile acids.

3. Formation of Bile Salts:

   • These bile acids are conjugated with either glycine or taurine, forming bile salts, which enhances their solubility and effectiveness in emulsifying dietary fats.

4. Storage and Release:

   • Bile salts are stored in the gallbladder and released into the small intestine during digestion to aid in the digestion and absorption of fats.

Conversion of Cholesterol into Steroid Hormones:

• Primary Location: Steroidogenic cells in the adrenal cortex, gonads, and placenta.

Steps Involved:

1. Cholesterol Transport:

   • Cholesterol is transported from the outer to the inner mitochondrial membrane by steroidogenic acute regulatory protein (StAR).

2. Initial Conversion:

   • Cholesterol is converted into pregnenolone by the enzyme cytochrome P450 side-chain cleavage enzyme (CYP11A1 or P450scc). This is the rate-limiting step in steroid hormone synthesis.

3. Steroid Hormone Synthesis:

   • Pregnenolone is then metabolized into various steroid hormones, including glucocorticoids, mineralocorticoids, and sex hormones (androgens, estrogens, progestogens) through a series of hydroxylation, oxidation, and isomerization reactions.

Conversion of Cholesterol into Vitamin D:

Process Overview:

• Involves processes in the skin, liver, and kidneys to produce active vitamin D.

Steps Involved:

1. Skin Reaction:

   • In the skin, 7-dehydrocholesterol is converted to previtamin D3 upon exposure to UVB radiation. Previtamin D3 then spontaneously isomerizes to vitamin D3 (cholecalciferol).

2. Liver Conversion:

   • In the liver, cholecalciferol is hydroxylated by the enzyme 25-hydroxylase (CYP2R1) to form 25-hydroxycholecalciferol (calcifediol).

3. Kidney Conversion:

   • In the kidneys, calcifediol is further hydroxylated by 1α-hydroxylase (CYP27B1) to produce the biologically active form, 1,25-dihydroxycholecalciferol (calcitriol).

4. Role of Calcitriol:

   • Calcitriol plays a crucial role in regulating calcium and phosphate homeostasis. It enhances the absorption of calcium and phosphate from the intestines and promotes bone health by regulating their levels in the blood.

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