Exam 6: 504 - Roberts - Cholesterol And Lipid Transport - Los

Front 1

Can cholesterol be synthesized endogenously and taken up via diet?

Back 1

Yes and yes

Front 2

What is cholesterol?

Back 2

Cholesterol is essential as membrane component, and steroid and bile acids precursor

Front 3

Is cholesterol synthesis a multistep process or a single step process? What supplies carbons to cholesterol synthesis?

Back 3

multistep process (20-30 steps)

All carbons are supplied by acetate (acetyl-CoA)

Front 4

What are the four main components of the biosynthesis pathway of cholesterol?

Back 4

mevalonate (Most important of all), isoprene units, formation of squalene, cyclization and further modification to form cholesterol).

Front 5

What are the four main steps of fcholesterol biosythesis?

Back 5

#1: Condensation of three acetate units to form mevalonate (C6)

#2 Conversion of mevalonate to activated isoprene units

#3: Polymerization of six 5C isoprene units to form the 30C linear squalene

#4: Cyclization of squalene to form the four rings of the steroid nucleus, with further changes (oxidation, removal or migration of methyl groups) to produce cholesterol

Front 6

What doesHMG-CoA reductase form?

Back 6

Mevalonate

Front 7

How is mevlaonate regulated?

Back 7

#1: Transcription – Transcription factor SREBP is regulated by the # of sterols

#2: Translation – presence of sterol inhibits (especially mevalonate derived sterol)

#3: Hormonal –
Insulin stimulates cholesterol synthesis by dephosphorlation and activation of HMG-CoA reductase

Glucagon – kinasee will phosphorylate HMG-CoA reducase and inhibit cholesterol production

#4: Product inhibition - If cholesterol levels get too high, they will cause HGM-CoA reductase to be destroyed = direct product inhibition

Front 8

How are lipids & fatty acids transported in blood? Can they be free?

Back 8

Transported as fatty acids by albumin; other lipids in lipoprotiens.

Cannot be free in blood!

Front 9

What are the three general components of lipoprotiens?

Back 9

#1: Core: Triacylglycerols, cholesteryl esters

#2: Phospholipid monolayer: phospholipids, cholesterol

#3: Protiens: different proteins combine with lipids (Apo)lipoproteins.

Front 10

What are chylomicrons and what is their role in lipid transport?

Back 10

Chilomicrons are transporters made of cholesterol esters and triacyglycerols.

They transport dietary triacylglycerols and cholesterol (about 5%)

Front 11

What are VLDLs and what is their role in lipid transport?

Back 11

Circulate in blood stream, uptake of fatty acids. High in fatty acids, low in cholesterol.

Front 12

What are IDLs and what is their role in lipid transport?

Back 12

Intermediate between VLDL and LDL – more dense than VLDL

Front 13

What are LDLs and what is their role in lipid transport?

Back 13

Fatty acids are being removed – becomes more dense as fatty acids make it boyant. % Cholesterol in LDL rises in comparison to VLDL as FAs are removed

- transport of endogenous triacylglycerols and cholesterol

Front 14

What are HDLs and what is their role in lipid transport?

Back 14

responsible for reverse reversal transport – but it also sops up cholesterol. Reverse cholesterol transport.

Front 15

Outline LDL uptake

Back 15

Docs to specific receptors (ApoB-100 binds to LDL receptor)– entire LDL is endocytosed and fuses with lysosome to free fatty acids, amino acids, cholesterol released into cytosol. Receptors are recycled

Front 16

Why is LDL a bad cholesterol and HDL a good cholesterol?

Back 16

Normal levels of LDL are good, only bad when there are too much – shown to contribute to plaque formation. HDL – works by sopping up cholesterol and take it away.

Front 17

What is the basic process of atherosclerosis?

Back 17

Starts with an arterial endothelial injury

If oxidation occurs during the inflamitory repair process, plaques arise as depositied lipids.

Can effect arteries of any tissue, causes cell damage and cell death.

Front 18

Define hyperlipidemia

Back 18

Hyperlipidemia (too much lipid)

Combined hyperlipidemia = both LDL and triglycerides

Front 19

Define hypolipidemia

Back 19

Hypolipidemia (too little fat)

Can lead to:
Abetalipoproteinemia: beta lipoproteins

Tangier disease: high density lipoprotein (HDL)

Front 20

What form of lipids are in each of the steps?

Back 20