Lipids And Lipoproteins Flashcards by Radhika Patel

How to make isoprenoids (IPP) and its significance

3 acetyl CoAs 
Precursor for
- steroids (cholesterol)
- Lipid vitamins 
-ubiquinone

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How does Acetyl Co A get into cytoplasm

Citrate shuttle

Made from pyruvate, aa, FAs in mitochondria

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6 units of IPP forms

Tetracyclic sterane ring

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Cholesterol is allicyclic meaning

OH at 3rd position

Hydrophobic and hydrophilic

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Cholesterol is precursor for

VIT D
Bile
Steroid hormones (E, P, Cortisol, Aldosteron, T)

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Breakdown of cholesterol

No enzymes Can only be excreted by in liver

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Daily cholesterol recommended intake and how much body makes

<300mg

0.75g-1.0g / day

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Synthesis of cholesterol needs what

18 ATP
18 Acetyl CoA
16 NADPH

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Phase 1 of cholesterol synthesis

3 AcetylCoA ——> IPP
2 Acetyl CoA (acetoacetyl CoA)—HMG CoA synthase—> HMG CoA
RLS : HMG CoA reductase (HMG CoA—> Mevalonate)

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Phase 2 of cholesterol synthesis

IPP ——> Cholesterol

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How is HMG CoA reductase functioning

Made in ER

Catalytic domain is on cytosolic side (where statins or HMG CoA binds)

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Inhibiting IPP synthesis by Statin can also inhibit what synthesis

Heme A
Ras protein
Ubiquinone
Dolichol

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Statin is what kind of inhibitor
Affinity
+ side effect of long term use
- side effects

Competitive inhibitor
Higher affinity
Transcription of LDL receptor for cells to take up cholesterol
Myotoxic: X ubiquinone——> fatigue and muscle death

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Direct and covalent modification to regulate HMG CoA Reductase

Direct : FFA, bile, oxysterol, statin
Covalent Modification : Phospholylation = inactivates, dephosphorylated = activated
* low energy = high AMP —> AMPK activated = phosphorylates it

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What dephosphorylates or phosphorylates HMG CoA Reductase

Phosphorylates: AMPK + Glucagon

Dephosphorylates : Insulin

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What can increase translation of HMG CoA Reductase

VIT E

HMG CoA Reductase TF and gene

SREBP (binds to SRE on promoter)

low cholesterol or on statin use : protease (SCAP) cuts of SREBP and it goes to Golgi —> Nucleus to activate SER on promoter
high cholesterol : INSIG keeps SREBP-SRE in ER

Lipoproteins function

Transport cholesterol, fat, VIT

Deliver TAGs from liver + GI to tissues
Deliver Cholesterol to liver for excretion
Activate enzymes for lipid metabolism

5 times fo Lipoproteins

Chylomicrons (biggest + lowest density)
LDL
HDL (smallest + highest density)
IDL
VLDL (second largest)

Chylomicrons vs HDL

Chylomicrons have a lot of TAGs

HDL has a lot of protein

Where are chylomicrons made

And composition

In intestinal cells
(From fat we eat)
Largest, lowest density,, highest TAGs
* has ApoB-48 : protein to help transport it
*ApoE : uptake to liver
*ApoC : activates capillary lipoprotein lipase to break it

Where are VLDL made

And composition

In liver
ApoC : activate capillary lipoprotein lipase
ApoE : uptake to liver
ApoB-100 : uptake into cells

IDL and LDL composition

IDL : ApoB-100 + ApoE

LDL : ApoB-100

LDL has high

Cholesterol

HDL composition

Smallest, most dense, high protein + phospholipids ApoC ApoE ApoA- 1 : activates enzyme to esterify cholesterol

Chylomicron Processing

1. Made in SI + package dietary fats 2. Go into lymph and BV : Nascent Chylomicron (ApoB-48) 3. Mature Chylomicron : ApoB-48 +ApoE + ApoC 4. ApoC is released and = Chylomicron remanent —> goes into liver*

Hyperlipoproteinemia Type 1 (familial hyperchylomicronemia)

X ApoC (adolescent) OR lipoprotein lipase(primary, in infancy) : no capillary lipoprotein lipase made to get fats into blood or tissues for exchange from the Chylomicron Sx: Xanthomas TX : low fat diet

Hyperlipoproteinemia Type 2

X ApoB-100 recognition : no uptake of fats X LDL receptor * Sx: dies form CAD (if homozygous) , Xanthomas

VLDL processing

1. Made in liver and release into Blood stream (ApoB-100,ApoE, ApoC) 2. Capillary LPL hydrolysis of glycerol to FFAs 3. ApoC released = IDL *

IDL fate

1. IDL can enter liver to release FFA in liver or stay in blood 2. IDL looses a lot of TAGs in liver and other tissues and looses ApoE = LDL*

LDL fate

1. LDL delivers cholesterol to liver and other tissues with ApoB-100 binding to LDL receptor (brings cholesterol into cells) * if too much it stays in BV and makes plaques

LDL is taken up to tissues by

Receptor- mediated Endocytosis ApoB-100 binding to LDL receptors LDL degraded by lysosome —> Cholesterol

Familial hypercholesterolemia

LDL receptors are unable to release the LDL bound to them | Mutated LDL receptors

HDL processing

1. Made in SI and liver as nascent HDL released in blood 2. They pick up cholesterol from tissues (ApoA-1) 3. LCAT : esterify cholesterol inside = mature HDL *

Other functions of HDL

1. Provide Chylomicron with ApoE and ApoC * (Chylomicron maturation) 2. Exchanges TAGS, cholesterol, cholesterol esters with LDL, IDL, VLDL * takes all esterified cholesterols to liver for excretion 3. Antioxidant, higher by exercise and weight loss, anti-diabetic

ABCA1 Function Loss of it causes

``` Transport protein that ApoA-1 binds to (of HDL) and transports LDL Tangier Disease (HDL deficiency and high cholesterol) ```

What happens with excess LDL

Oxidized to oxLDL which is deposited in the BVs | = injury = inflammatory response = macrophages become foam cells = platelet adhesion + SM recruited = bigger plaque