L36: Cholesterol Metabolism

Question 1

Where is de novo synthesis of cholesterol taking place?

Answer 1

Where:
Tissue location: cholesterol is synthesized by virtually all tissues in humans, although liver, intestine, adrenal cortex, and reproductive tissues (e.g. ovaries, testes, and placenta) make
the largest contributions to the body’s cholesterol pool.
Cellular location: reactions occur in the cytosol with enzymes in the cytosol or associated with the SER membrane.

Question 2

When is de novo cholesterol synthesis taking place?

Answer 2

When: it is generally active during the fed state (a high I/G ratio).
The starting substrate is cytosolic acetyl-CoA, the same source for de novo fatty acid synthesis pathway.
It is an anabolic pathway, and it requires the high energy molecules such as ATP and NADPH. NADPH is produced by the oxidative branch of HMP shunt and malic enzyme.