Lecture Notes

Lipid transport & steroid biosynthesis
Learning objectives:

1. Describe the function of lipoprotein in cholesterol and triglycerides transportation
2. Uptake of LDL particle into tissues
3. describe the role of HDLS
4. understand the aetiology of diseases associated with lipid transport
5. describe the role of P450 in the production of steroids and cholesterol
6. explain in general the key stages of steroid biosynthesis

LO1. DESCRIBE THE FUNCTION OF LIPOPROTEIN PARTICLES IN CHOLESTEROL AND TRIGLYCERIDES

low density lipoproteins major C & CE carrier in blood

 carry cholesterol to peripheral tissues and is the major carrier of C in the blood
 diameter of approx. 22 nm and contains a core of around 1500 CEs.
 A shell of phospholipids and C surround the CEs
 shell also contains a single copy of the Apo-B-100
 tissues have specific surface receptors that recognise Apo-B100 (major apoprotein)
 Apo-B100 receptors mediate uptake of cholesterol & cholesteryl esters




LO3. DESCIRBE THE ROLE OF HDLS

High density lipoprotein HDL

 Assembled from components obtained from liver and gut small protein rich ‘’empty’’ particles
 Contain:
- Apo-CI
- Apo-CII
- Lecithin cholesteryl transferase (LCAT)
 major role is to pick up cholesterol released into plasma from dying cells and from membranes
undergoing turnover.
 LCAT (produced in liver) esterifies these cholesterols, which are then either rapidly shuttled to
VLDL or LDL by a specific transfer protein or returned by HDL to the liver.
 LCAT is vital as it
- Forms cholesteryl esters from lecithin (phosphatidyl choline) & cholesterol
- Transfer to LDL particles

, Blood levels of lipoproteins- diagnostic purpose

 High serum levels of cholesterol is bad
- Result in diseases and deaths by contributing to the formation of atherosclerotic plaques
in arteries throughout body.
- Atherosclerotic = pertaining to atherosclerosis, the process of progressive thickening and
hardening of the walls of arteries from fat deposits on their inner lining
- Atherosclerotic heart disease is the leading cause of death in the US.
 Excess cholesterol in form of LDLs is called ‘bad’ cholesterol
- Ratio of LDL to HDL is important as HDL is ‘good’
As the HDL binds and esterifies cholesterol released from tssues, then transfer to
liver or tissues needing C to create steoids
- Normal LDL to HDL is 3.5
- Exact reason for why DL levels protect you is not known.

LDLs and cholesterol metabolism

 Cholesterol levels are important in preventing atherosclerosis
- Mode of control in liver (hepatic cells) already discussed (control of CoA reductase)
- Body also needs to tightly regulate also in non-hepatic cells
- Cells outside liver get cholesterol from plasma and the LDL (do not synthesise)
 Process of uptake is called receptor mediated endocytosis
- Good paradigm (typical example) for uptake of many molecules.
- First LDLs exit blood stream through capillary pores and vesicular transport across
endothelium
- Second LDLs absorbed in peripheral tissues
 Finally receptor mediated endocytosis done in 3 steps

LO2. UPTAKE OF LDL PARTICLE INTO TISSUES

Receptor mediated endocytosis

1. Apo B-100 protein of LDL surface is recognised by receptor proteins on plasm surface.
- These are localised in special regons called clathrin coated pits (due t prescence of a
protein called calthrin)
2. Receptor-LDL comples internalised by endocytosis leaving a endocytic vesiclein the cell
3. These vesicles fuse with lysosomes (acidic vesicles that carry loads of) degrative enzyes.
- The enzymes breakdown the protein and turn CE back to C through hydrolysis reactions.
- Receptor then returned to cell surface minus C.