cholesterol can be synthesised via two different pathways known as exogenous or endogenous pathway.
usually cholestrol is gained via the exogenous pathway (food entering) and the food breaks down into cholestrol (will be explained in detail below). however if for some reason there is an insufficient supply from food then the endogenous pathway can be used, it is the pathway which involves the use of acetyl CoA being used in the SER & cytosol to become cholestrole this makes up 20% of the endogenous cholestrol and the other 80% is made by the VLDL pathway eventually becoming LDL and being endocytosed into the liver and broken down into constituent parts requered for bodily function such as steroid hormone synthesis
(good to note HMG-Co reductase is the rate limiting step and this is also the step that statins inhibit).
the exogenous pathway is stimulated by food entering the stomach and being broken down into fatty acids, triglycerides, cholesterol etc, these breakdown products are found within enterocytes (lining of the gut). an enzyme known as ApoB48 then acts as a scaffolding for these breakdown products to stick to, as they all converge together it becomes a nascent chylomicron (immature chylomicron). at this point the nascent chylomicron is then released from the enterocyte into lymph vessels where it eventually exits through the thoracic duct into the plasma (blood stream). when the nascent chylomicron is within the blood stream it has a brief connection with HDL where it gains ApoE and ApoCll. ApoE is a protein which allows the chylomicron to bind with the liver and ApoCll is a Lipoprotein Lipase (LPL) co-factor (it helps to stimulate LPL). once the chylomicron has received these proteins it is now known as a Mature chylomicron. the mature chylomicron enters the blood stream capillary regions of cardiac, skeletal and adipose tissue and muscle. as it enters there is a protein known as Lipoprotein lipase LPL present within the capillaries it is activated by insulin and ApoE (insulin is present because of the metabolism that goes alongside the meal that is being digested). as the LPL is activated it acts to break down triglycerides that are present within the centre of the mature chylomicron it breaks them down into 2 things - fatty acids which are then reabsorbed either as adipose tissue or energy and glycerol, the glycerol can either be taken up by the liver to help in gluconeogenesis. or it can be repackaged as triglycerides again. after this process the chylomicron is now known as a remanent chylomicron these are then directed to the liver where they are endocytosed inside and are broken down for their remaining properties and most notably vitamin A content.
the endogenous pathway is very similar to the above one, however there are a few differences…
the scaffolding protein is different and is known by ApoB100
also the chylomicron is known as nascient VLDL mature VLDL ….
as the endogenous pathway is activated internally due to lack of dietary cholesterol there is no insulin present to activate and stimulate LPL and therefore the ApoCll on the mature VLDL is the only stimulant for LPL. after that the mature VLDL becomes an intermediate density lipoprotein (IDL). and then once it donates ApoE to HDL it becomes LDL which is endocytosed by the liver and broken down into its constituents.
