biochemistry 6 Flashcards
what is the structure and characteristics of cholesterol
- steroid with 4 linked hydrocarbon rings
- hydrocarbon tail and hydroxyl group at opposite ends
- highly hydrophobic and insoluble in water
what is the functions of cholesterol
- modulates membrane fluidity
- some nerve cells have 25% in the plasma membrane
- precursors to steroid hormones and bile salts
where is cholesterol mainly synthesised and what does it require
- the liver
- ATP and NADPH
what are the stages of cholesterol synthesis
1) acetyl CoA converted to mevalonate - cytoplasm
2) mevalonate is used to synthesise isopentenyl pyrophosphate - cytoplasm
3) 6 molecules of isopentenyl pyrophosphate condense to form squalene - ER
4) squalene cylizes to lanosterol
5) lanosterol converted into cholesterol - ER
what is the name of the first step in cholesterol synthesis and what enzyme is used
- commitment step
- HMG-CoA reductase
what is required for the second step of cholesterol synthesis
- 3ATP and one decarboxylation
how many isomers of isopentenyl pyrophosphate are there and are they in equilibrium
- 2 isomers
- in equilibrium
what is added in stage 3 of cholesterol synthesis and how do they combine
- two additional isopentenyl pyrophosphates added to form farnesyl pyrophosphate
- tail-tail coupling of farnesyl pyrophosphates yield squalene
how is squalene activated
- activated with the formation of squalene epoxide
what does squalene epoxide form
- protonated to form carbocation that cylizes to form a tetracyclic stricture
what is HMG CoA reductase activity controlled by
- mRNA controlled by sterol regulatory element binding protein (SREBP)
what happens when HMG CoA reductase becomes inactive
- high cholesterol
- SREBP bound to SREBP cleavage activating protein (SCAP) at ER
what happens when cholesterol levels decrease
- SCAP escorts SREBP to the golgi
- golgi serine and matalloprotease act of SREBP
- DNA-binding domain moves to the nucleus to alter HMG CoA reductase gene expression
what happens when cholesterol levels are high
- mRNA controlled by SREBP
- mRNA negative feedback by metabolites of mevalonate
- HMG CoA reductase degradation with high cholesterol
- AMP-activated kinase phosphorylates and inactives HMG CoA reductase
what are the sources of cholesterol
- meats
- dairy products
- cakes and biscuits
- foods containing coconut oil or palm oil
how is cholesterol absorbed in the body
- intestine by sterol transporters
- cholesterol esterified by Acyl-CoA-cholesterol acyltransferase-2
- incorporated into chylomicrons - lipoprotein
what are lipoproteins
- soluble protein-lipid particles
- proteins component use to target to specific tissue
what is a chylomicron
dietary lipids and cholesterol
what is a low-density lipoprotein (LDL)
- supplies cholesterol to tissues
- receptor mediated endocytosis by LDL receptor binding internalisation (recycled after) and LDL hydrolysis
what is a high-density lipoprotein
- removes free cholesterol from tissue
- transports cholesterol to liver
what does the liver do with cholesterol
- eliminates cholesterol from the body as bile salts or unchanged
what steroid hormones and vitamins does cholesterol make
steroid hormones - progesterone, testosterone, oestrogen, cortisol
vitamins - D, calcium, phosphorus
what are bile salts
- detergents that render dietary lipids more accessible for digestion by lipase
- made from cholesterol
what is dietary lipids function
- fatty acids are main lipid constituent of diet
- primary role in energy metabolism - beta oxidation and energy storage
what is the luminal phase of degradation of dietary lipids
1) lipases secreted near tongue and stomach - some lipids hydrolysed into glycerol and free fatty acids
2) emulsification in the stomach - small lipid droplets form
3) bile salts used to form micelles allowing lipase access
4) pancreatic impasse complete hydrolysis in duodenum and jejunum
what happens in the mucosal phase in the degradation of dietary lipids
- fatty acids —-> Acyl-CoA derivatives
- cytoplasmic surface of ER - esterifcation of fatty acids to triacylglycerol
monoacylglycerol + Fatty acyl-Co-A —-> diacylglycerol + fatty acyl-Co-A —–> triacylgycerol
1) monoacylglycerol transacylase
2) diacylglycerol transacylase
what happens in secretion/ transport in the degradation of dietary lipids
1) in the gut, triacylglycerols accumulate in chylomicrons
2) chylomicrons exocytosed into blood via lymphatic system
3) blood lipase hydrolyse chylomicrons into fatty acids
4) fatty acids taken up by tissues
5) chylomicron remnants taken up by liver - rich in cholesteryl ester and fat soluble vitamins
what do apolipoproteins do
- act like postcodes
- regulate lipase activity
what stimulates/ decreases lipoprotein lipase activity
apoliproteins - apoC -1,2,3,5,E - stimulates activity
angiopoietin like proteins - ANGPTL3,4,8 - converts active lipase dimer to inactive monomers
