Cholesterol Flashcards
What is the structure of cholesterol?
Steroid with planar cyclic rings. It has a hydrophobic tail and is overall very hydrophobic made only of carbon and hydrogen atoms, apart from a single OH group at C3.
Where is most of our cholesterol found?
In our cell membranes, where it influences the fluidity of the membrane.
Where is most of our cholesterol from?
De novo synthesis from acetyl CoA by the liver.
What are the three main parts of the cholesterol synthesis pathway?
Synthesis of the isopentenyl pyrophosphate, an activate isoprene which is a key building block of many molecules - in the cytoplasm.
Condensations of six molecules of isopentenyl pyrophosphate to form squalene - in the cytoplasm.
Cyclization and demethylation of squalene by monooxygenases to make cholesterol - in the ER.
How is the formation of cholesterol regulated?
The enzyme in step 3 of the synthesis, HMG-CoA reductase is under negative feedback control by cholesterol, the intermediate formed by that reaction mevalonate and bile salts.
What is especially useful about isoprene units?
They can confer lipophilicity to biomolecules.
What is the link between isoprene and the electron transport chain?
Isoprene confines ubiquinone (coenzyme Q) to the inner membrane of the mitochondria.
What is the major breakdown product of cholesterol?
Bile salts (glycocholate and also taurocholate). The hydrophobic parts of cholesterol aid its function, with polar groups added onto parts to give it both hydrophilic and hydrophobic parts.
Apart from bile salts, what else can cholesterol be used to synthesize?
Steroid hormones - the precursor of all steroid hormones, pregnenolone, is generated from cholesterol by the action of desmolase.
Vitamin D metabolites - The main source of vitamin D in western cultures is from the activity of UV light upon 7-dehydrocholesterol in the epidermis of the skin.
What is vitamin D?
Vitamin D is a collective term for a group of steroids that are vital for the intestinal absorption of important ions needed for bone development, namely calcium, phosphate, and magnesium.
What is calcitriol?
Calcitriol is the most active vitamin D metabolite and plays a key role in calcium metabolism. It functions as a steroid hormone, binding to vitamin D response elements (VDREs) in the promoter of target genes and inducing key genes involved in bone metabolism.
What can a deficiency in Vitamin D3 cause?
A deficiency of Vitamin D3 in childhood leads to rickets, a defect of bone development in children.
What is familial hypercholesterolaemia?
FH) is a monogenic dominant trait in which cholesterol transportation is defective, causing high levels of cholesterol in the blood.
Heterozygotes with FH have cholesterol levels about 2-3 times higher than in normal people. What will this make them susceptible to?
Atherosclerosis and subsequent CVDs.
How may heterozygotes with FH compare to homozygotes? What would you expect to see?
Macrophages can also pick up cholesterol from LDLs and are present in the skin. What may this form?
Much more severe symptoms.
Much higher serum cholesterol levels leading to:
Severe atherosclerosis and CVDs from an early age.
Macrophages scavenging cholesterol from LDLs can lead to cells to swell with cholesterol, forming orange-yellow xanthomas lying superficially above the knees, wrists, and hands.
