Lipids 4 Flashcards
What makes cholesterol useful?
That it’s Janus-faced and has insolubility in water
Sources of cholesterol?
- Diet eg eggs, liver, fish
- De novo synthesis (adults on low cholesterol diet synthesis around 800mg cholesterol per day), cells can’t degrade steroid nucleus, excreted by the liver (in bile), consume it biochemically
What’s the major site of cholesterol synthesis?
Liver (needs to be tightly regulated)
Where are all 27 carbons of cholesterol derived from?
Acetyl CoA in 3 stages
3 stages synthetic process that cholesterol gains 27 carbons?
- Synthesis of isopentenyl pyrophosphate, an inactivated isoprene that is the key building block of cholesterol
- Condensation of 6 molecules of isopentyl pyrophosphate to form squalene
- The cyclisation of squalene in an “outstanding reaction” and the tetracyclic product is subsequently converted into cholesterol
Where do the three stages of cholesterol synthesis located?
1= cytoplasm 2,3= endoplasmic reticulum
What’s the committed step of cholesterol formation?
Synthesis of mevalonate
What catalyses the synthesis of mevalonate?
HMG-CoA reductase
What is the intermediate in the first step of cholesterol synthesis?
HMG-CoA (from acetyl CoA and acetoacetyl CoA)
Four ways HMG COA reductase controlled?
- Rate of synthesis
- Rate of translation
- Rate of degradation
(1-3 alter the amount of enzyme more than 200 fold) - Phosphorylation of the reductase reduces its activity
What are potent competitive inhibitors of HMG-CoA reductase?
Lovostatin and related compound
What is another method on inhibiting cholesterol levels?
Inhibiting intestinal reabsorption of bile salts (bile salts ate cholesterol derivatives that promote the absorption of dietary cholesterol and dietary fats)- this is the oral administration of positively charged polymers (eg cholestyramine) that bind negatively charged bile salts
What transports cholesterol throughout the organism?
Lipoproteins
What are lipoproteins comprised of?
A core of hydrophobic lipids surrounded by a shell of more polar lipids and proteins
What can lipoprotein particles shift between?
Classes as they release or pickup cargo, thereby changing their density