Lecture 14 Flashcards
What are the main precursors of cholesterol synthesis?
acetyl-CoA, acetate, mevalonate (committed step), DMAPP and IPP
Where does cholesterol synthesis occur?
Cytosol
Which enzyme is found in cholesterol synthesis but not ketogenesis?
HMG-CoA reductase
What is step 1 in cholesterol synthesis? What’s this reaction called?
React DMAPP and IPP to form geranyl pyrophosphate (10-C). This reaction is called “head-to-tail condensation”
What is step 2 in cholesterol synthesis (Starting from DMAP and IPP)?
Geranyl pyrophosphate combines with isopentyl pyrophosphate to form farnesyl pyrophosphate.
Big picture: combine two pyrophosphates to make an even bigger pyrophosphate
What is step 3 in cholesterol synthesis?
Reduce farnesyl pyrophosphate with NADPH + (H+) to form squalene
What is step 4 in cholesterol synthesis?
Add oxygen, reduce squalene with NADPH to form squalene 2,3 epoxide + water and NADP+
What is step 5 in cholesterol synthesis?
Form lanasterol
What is the last step in cholesterol synthesis?
Multistep process from lanasterol to cholesterol
What is step 1 in the exogenous pathway of cholesterol transport?
Cholesterol moves directly into intestinal mucosal cells to be packaged into chylomicrons
What is step 2 in the exogenous pathway of cholesterol transport?
Chylomicrons travel through blood vessels. Body cells recognize apolipoproteins if they need fat (i.e., adipose ,muscle, adrenal gland, gonads…etc)
What is step 3 in the exogenous pathway of cholesterol transport?
Chylomicron remnants (what’s left after delivery to the body tissues) go to the liver
What is step 1 in the endogenous pathway of cholesterol transport?
Cholesterol is converted to cholesteryl esters (CE) in the liver.
What are cholesteryl esters and why are they useful?
They’re cholesterol but with long hydrocarbon tails, which is useful for packing in transport
What is step 2 in the endogenous pathway of cholesterol transport?
Cholesteryl esters are packaged into VLDLs
What is step 3 in the endogenous pathway of cholesterol transport?
VLDLs go from the liver to the tissues in the blood
What is step 4 in the endogenous pathway of cholesterol transport?
Lipases remove FAs from VLDLs, which convert them to LDLs
What is step 5 in the endogenous pathway of cholesterol transport?
Unused LDLs return to the liver via LDL receptors
What happens to a person with mutant LDL receptors?
They suffer from high cholesterol levels since the LDLs can’t enter the liver to be excreted or used
Describe the process of artery occlusion due to high cholesterol levels
Monocytes are attracted to oxidized lipoproteins that have stuck to the extracellular matrix. They differentiate into macrophages, which cannot control how much cholesterol they take up. Eventually, they take up so much fat that they form foam cells, which eventually commit apoptosis. Plaques form from dead foam cells, cholesterol, lipoprotein, and lipid buildup
What are polyketides?
They are specialized lipids typically found in bacteria. They form antibiotics.
What are terpenes?
They are specialized lipids typically found in plants and give them aroma
What are the precursors of polyketides and terpenes?
acetate, acetyl-CoA, IPP, and DMAPP
What is the monomer in polyketides?
Malonyl-CoA
How many types of polyketide synthases are there?
3
Describe Type I polyketide synthases
There’s a single protein with many modules. Each active site is only used once. Product is predictable.
Describe Type II polyketide synthases
There are multiple proteins that can be used once or many times. Product cannot be predicted
Which enzymes are needed to add a malonyl-CoA unit every time?
Ketone synthase (KS) and transacyltransferase (AT)
What does ketoreductase (KR) do? What happens if it’s not present?
It reduces carbonyls to alcohols. Without it, you’re left with a carbonyl
What does dehydratase (DH) do? What happens if it’s not present?
It oxidizes alcohols to carbon-carbon double bonds. Without it, you’re left with an alcohol
What does enoyl-reductase (ER) do?
It reduces carbon-carbon double bonds to hydrocarbons. Without it, you’re left with a carbon-carbon double bond
How many carbons are in a terpene? Diterpene?
10
20
