Cholesterol Metabolism

Cholesterol is present in tissues and in plasma either as free cholesterol or as a storage form, combined with along-chain fatty acid as cholesteryl ester. In plasma, both forms are transported in lipoproteins .
Functions of Cholesterol
Cholesterol is an amphipathic lipid and as such is an essential structural
1. Integral Membrane component
2.Bile acids/salts precursor
3.Vitamin D3 precursor
4. Steroid Hormone Precursors as Male sex hormones (testosterone, other androgens) & Female sex hormones (Estrogens) and Adrenal cortex hormones as (glucocorticoides cortisol& Mineralocorticoides aldosterone).

Biosynthesis of Cholesterol
The synthesis and utilization of cholesterol must be tightly regulated in order to prevent over-accumulation and abnormal deposition within the body. Of particular importance clinically is the abnormal deposition of cholesterol and cholesterol-rich lipoproteins in the coronary arteries. Such deposition, eventually leading to atherosclerosis, is the leading contributory factor in diseases of the coronary arteries.

Cholesterol synthesis in microsomal (endoplasmic reticulum) and cytosol fraction of the cell is responsible for cholesterol synthesis from the two-carbon acetate group of acetyl-CoA. A little more than half the cholesterol of the body arises by synthesis (about 700 mg/dL), and the remainder is provided by the average diet. The liver and intestine account for approximately 10% each of total synthesis in humans. Virtually all tissues containing nucleated cells are capable of cholesterol synthesis, which occurs in the endoplasmic reticulum and the cytosol.
The acetyl-CoA utilized for cholesterol biosynthesis is derived from an oxidation reaction (e.g., fatty acids or pyruvate) in the mitochondria and is transported to the cytoplasm by the same process as that described for fatty acid synthesis. All the reduction reactions of cholesterol biosynthesis use NADPH as a cofactor
Pathway for the movement of acetyl-CoA units from within the mitochondrion to the cytoplasm for use in lipid and cholesterol biosynthesis. Note that the cytoplasmic malic enzyme catalyzed reaction generates NADPH which can be used for reductive biosynthetic reactions such as those of fatty acid and cholesterol synthesis.