Cholesterol 1 Flashcards
What are the structural features of cholesterol?
It is a saturated tetracyclic H-Carbon A, B, C, 6 Membered Rings D 5 Membered ring Aliphatic chain at C17 Axial CH3 groups at C10 and C13 Double bond in ring B 3-OH in ring A Cyclohexane in chair conformation Cholesterol is flat an compact
How is cholesterol synthesized?
Made largely in the liver though can also be made in the brain and intestine
All Carbon atoms come from acetyl coA
How is acetyl coA converted to activated isoprenes IPP and DPP?
Acetoacetyl-CoA combines with an acetyl coA to produce 3-Hydroxy-3-methylglutaryl-coA
This then reacts with and NADPH and 2H+ via HMG-CoA reductase to form Mevalonate through release of the coA group
Mevalonate is then activated by three phosphorylations ( 5phosphomevalonate to 5 pyrophosphomevalonate to 3phospho5pyrophosphomevalonate)
The molecule then undergoes an ATP dependant decarboxylation where a phosphate and CO2 groups are lost
This forms IPP (Isopentenyl pyrophosphate) which can isomerie to give DPP (dimethylallylpyrophosphate)
What is the rate limiting step in Cholesterol synthesis?
The conversion of 3-hydroxy-3methylglutaryl-coA to mevalonate via HMG-coA reductase
How is HMG-coA reductase regulated?
Regulated in response to cholesterol levels by both alterations in gene transcription and degradation of the protein
How do the isoprene units contribute to squalene synthesis?
The two isoprene 5 carbon units combine to give geranyl pyrophosphate, and one more isoprene 5 carbon unit combines with this to give a 15 carbon unit of farnesyl pyrophosphate
Two of these farnesyl pyrophosphates will combine through a condensation reaction of their tails to form squalene
How does squalene contribute to cholesterol synthesis?
Reacts with mixed function oxidase enzyme and undergoes various protonations to give shifts of methyl groups and hydride ions to give lanosterol, roughly 20 reactions follow to finally give cholseterol
What is the relationship between cholesterol and bile salts?
Cholesterol is required for the synthesis of bile salts, is the only excretion mechanism the body has for cholesterol as bile salts are lost through the bile with 20-30g being secreted per day and 0.5g elminated
Most are recycled from lower intestine to the liver through enterohepatic circulation
What are the properties of bile salts?
Have detergent properties due to their amphipathic nature and can be used for fat digestion and adsorption
They are cholesterol derivatives where all have extra OH groups, the first to be added during their synthesis is always a 7-OH and is the rate determining reaction, some also have an 17-OH group
The COOH group on the sidechain is often conjugated to amino acids glycine or taurine to give bile salts glycocholate and taurocholate
What is the relationship between cholesterol and hormones
Cholesterol is the precursor of all steroid hormones
Cholesterol esters are hydrolysed to cholesterol which is taken into the mitochondria
Converted to pregneolone by cytochrome P450 enzyme
What are the Steroid synthesising tissues?
adrenal cortex, ovary and testis which contain lipid
droplets (cholesterol esters) in the cytoplasm
