Steroid Hormone Biosynthesis Part 1 Flashcards
What is the precursor of steroids, and the forms of it found in the body?
- cholesterol (membrane lipid)
- associated with apoprotein, triglycerols and phospholipids in lipoproteins in plasma
- in cytosol are cholesterol esters
What is cholesterol synthesised from and where does the process occur?
- in the liver from acetyl CoA
- in the smooth endoplasmic reticulum and the cytosol
What is the rate-limiting step of cholesterol biosynthesis?
conversion of HMG-CoA to mevalonate by HMG-CoA reductase
What is the importance of the rate-limiting step of cholesterol biosynthesis, and what can inhibit it?
- the enzyme activity can be adjusted to regulate the levels of cholesterol in the plasma
- the enzyme is inhibited by statins
Describe the classification of the major classes of plasma lipoproteins
- classified on lipoprotein amount and side
- chylomicrons are largest lipoprotein
- VLDL, IDL, LDL and HDL are other classes (getting progressively smaller in size and increase in density)
Describe the features of the classes of plasma lipoproteins
- all stem from LDL which is made in liver and transported into circulation
- role is to take glycerols and triacylglycerols and supply them to tissues around the body
- HDL is also made by the liver and put into circulation
- VLDL gets altered into different particles
Describe the exogenous pathway of cholesterol metabolism
- gut absorbs all fats coming into gut
- epithelial cells of gut make chylomicrons
- transported out by epithelium and into circulation
- in plasma go through different tissues
- tissues that have adipocytes on outside of cells have lipoprotein lipases (LPL) that break down triacylglycerols in chylomicrons to release free fatty acids and glycerol to be taken up by tissues and adipocytes
- muscles use this for energy
- adipocytes resynthesise triacylglycerols and store them as fats
- left with remnant chylomicrons
- liver takes cholesterol and with what it can synthesise with what is left of the remnant chylomicrons it packages it with lipoproteins making VLDLs which are exported back into circulation
What is cholesterol from the gut being used to synthesise and describe that pathway?
- bile acids
- stored with cholesterol in gallbladder
- can be excreted back into the gut and with cholesterol can help emulsify fats from the diet
- most bile acids and cholesterol is reabsorbed
What happens to the remnant chylomicrons?
- taken up by liver in endocytotic pathway
- fused with lysosomes to release contents to be broken down
What is contained in chylomicrons?
- high level triacylglycerols, cholesterol, cholesterol esters and proteins
Describe the endogenous pathway of cholesterol metabolism
- LDLs synthesised in liver and taken to systemic circulation
- LPL on adipocytes on cells cleaves triaglycerols to release fatty acids and glycerol for tissues to use
- causes depletion of triaglycerol
- causes rearrangement of proteins in particle
- starts taking up cholesterol esters from HDLs
- added to VLDLs, IDL and LDL by cholesterol-ester transfer protein
- LDLs taken up by specific endocytotic pathway by cells that need high cholesterol
What is the role of HDL
- take up excess/unesterified cholesterol from tissues and circulation
- enzyme LCAT esterifies the cholesterol molecules taken up
- then can be transported to VLDLs and LDLs by other enzyme
What cells need a lot of cholesterol?
cells that synthesise steroid hormones
Describe the endocytosis of cholesterol by cells that synthesise steroids
- LDL particle has apoproteins (Apo-B-100) on outer surface
- cells have receptors specific to Apo-B-100 protein
- binding causes signal transduction event leading to endocytosis of particle into cell
- mediated by complex protein network that surrounds the cell (clathrin)
- depolymerisation of clathrin to uncoat vesicle and fuse with lysosome that contains proteolytic enzymes
- breaks down apoproteins and cholesterol esters
- gives free cholesterol, amino acids, fatty acids and glycerol release
- cholesterol is free and can diffuse out and be stored as lipid droplets in cells or used directly to make steroids
Describe the process of using cholesterol to make steroids in cells
- can be processed into precursor for steroid hormone pregnenolone
- depending on pathway and cell type can form mineralcorticoid aldosterone, glucocorticoid cortisol or sex steroids
