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NA > L14: Cholesterol Metabolism and Membranes > Flashcards

L14: Cholesterol Metabolism and Membranes Flashcards

1
Q

Cholesterol Synthesis

Summarize the 4 steps of cholestoral synthesis

A

1) Synthesis of mevalonate from acetate
2) Activated isoprene production
3) Condensation of activated isoprene units
4) Cyclization of squalene

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2
Q

Cholesterol Synthesis

4 Steps of Cholesterol Biosynthesis

A
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3
Q

Cholesterol Synthesis

What is Oxidosqualene cyclase?
What are it’s 2 properties?

A

1) Catalyzes Cyclization reaction

2) Membrane insertion of product

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4
Q

Cholesterol Synthesis

Within the Cholesterol Metabolism sequence what enzyme is a major point of regulation?

What can this enzyme help with?

A

Major point of regulation: HMG-CoA reductase

Target of many cholesterol-lowering drugs, which act as competitive inhibitors

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5
Q

Cholesterol Synthesis

What is Cholesterol metabolism stimulated by?

What is Cholesterol metabolism inhibited by?

A

Stimulated by Insulin:

Inhibited by: Low ATP, glucagon, oxysterol

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6
Q

Cholesterol Synthesis

What are the fates of cholesterol?

A

Cholesterol ester and hormones

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7
Q

Cholesterol Synthesis

What are the metabolic fates of cholesterol?

A

Cholesterol ester and hormones

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8
Q

Lipid Energetics

Describe the Dispersion of lipids in H20?

A
  • Make the water more ordered
  • Entropy DECREASED
  • Unfavorable because nature always pushes towards more disorder (aka Entropy INCREASING)
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9
Q

Lipid Energetics

What are the 3 formations that lipids take in water?

A
  • Micelle
  • Bilayer
  • Vesicle
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10
Q

Membrane composition

How do the composition of lipids vary?

How do they affect the fluidity of the membrane?

A
  • More saturated = tighter compaction -> less fluidity and higher melting point
  • Longer fatty acid -> higher melting point
  • Membrane fluidity is physiologically regulated
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11
Q

Membrane composition

Describe sterols in the context of membrane composition
- What do they interfere with

A

Sterols are membrane plasticizers
- Interfere with motion of FA side chains
- Prevent highly ordered packing

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12
Q

Membrane composition

What happens to membrane composition at high temperatures?

What raises the melting point of membrane?

A
  • Membrane starts to melt
  • Cholesterol raises the MP of membrane
  • Addition of unsaturated phospholipids
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13
Q

Membrane composition

What happens to membrane composition at high temperatures?

What does cholesterol prevent?

A
  • Membrane starts to freeze
  • Cholesterol PREVENTS ordered packing and INCREASES fluidity
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14
Q

Lipid Diffusion

Describe the relationship between lipids and diffusion within the planes of membranes?

What is lipid diffusion driven by?

A

Lipids diffuse rapidly LATERALLY within the plane of membranes

Lipids diffuse very slowly VERTICALLY across membranes

Driven by Monomeric, Oligomeric, ATP-driven

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15
Q

Lipid Diffusion

What are the enzymes that catalyze VERTICAL lipid diffusion across membranes?
- What are their mechanisms?
- What are they dependent on?

A
  • Flippase: outside to in; ATP dependent
  • Floppase: inside to outside; ATP dependent
  • Scramblase: either direction; ATP independent
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16
Q

Lipid Diffusion

Describe the process of FRAP (Fluorescence Recovery After Photobleaching)

A

1) Stain the whole bilayer with florescence
2) Use a high-power laster to get rid of the florescence at a specific area of the bilayer
- Observe lateral diffusion of phospholipids because florescence will migrate to the “photobleached” area of the bilayer

17
Q

Membrane Proteins

What is an Integral protein?

A

An integral protein is inserted into a large part of the membrane and can span thru the membrane

18
Q

Membrane Proteins

How are Integral proteins removed?

A

With detergents or organic solvents (which disrupts the hydrophobic interactions)

19
Q

Membrane Proteins

Describe Amphitropic proteins?

A

NOT embedded in the membrane

20
Q

Membrane Proteins

How are Amphitropic proteins removed?

A

Removed by pH, chelating agents, other mild treatments

21
Q

Membrane Proteins

What does a Hydropathy plot do?

What is on the Y axis?

What is on the X axis?

A

Shows hydrophobic vs. Hydrophilic character of side chains given a protein sequence

Y axis: Hyrdropathy index
(pos= hydrophilic) (neg= hydrophobic)

X axis: residue numbers

22
Q

Membrane Fusion

What are the 3 steps in Membrane fusion?

A

1) Joining
- Vsnares with NTs interact with t-SNARES plasma membrane

2) Hemifusion
- Inner leaflets come into contact as tension builds i on bilayers due to zipping of SNARES

3) Complete Fusion
- Pore widens, NTMs released

23
Q

Membrane Fusion

What are the 3 Models for protein-induced membrane curvature?

A

Model 1: Protein with intrinsic curvature

Model 2: Protein with one or several amphiphatic helices that force the membrane to bend

Model 3: Proteins with BAR domains polymerize into superstructures that force the membrane to bend

24
Q

Solute Transport

What are the two ways that molecules can travel though membrane channels?

Describe the mechanism behind each

A

Uniport: one molecule travels though channel

Cotransport: two molecules traveling at once

25
Q

Solute Transport

What are the two modes of Co transport?

Describe them

A

Symport - same direction

Antiport - opposite directions

26
Q

Solute Transport

What are the six different types of solute transport?

A

1) Simple diffusion
2) Facilitated diffusion
3) Primary active transport
4) Secondary active transport
5) Ion channel
6) Ionphore-mediated ion transport

27
Q

Solute Transport

Describe Simple Diffusion
- Mechanism
- Accepted compounds

A

Down concentration gradient; no help needed
- non polar compounds only

28
Q

Solute Transport

Describe Facilitated Diffusion
- Mechanism
- Accepted compounds

A

Down concentration gradient w/ help of channel
- Polar/ charged compounds

29
Q

Solute Transport

Describe Primary active transport
- Mechanism
- Drive

A

Against gradient; driven by ATP

30
Q

Solute Transport

Describe Secondary Active transport
- Mechanism
- Drive

A

Against gradient; driven by other molecules

31
Q

Solute Transport

Describe ion channel
- Mechanism
- Selectivity

A

Down electrochemical gradient; selective; may be gated

32
Q

Solute Transport

Describe Ionophore-mediated ion transport
- Mechanism
- Selectivity

A

down electrochemical gradient

33
Q

Solute Transport

What are active transporters?

A

Primary & Secondary

34
Q

Solute Transport

What are the passive transporters?

A

Facilitated diffusion, ionophore, ion channels

35
Q

Lipoproteins

Describe the interaction between lipids and hydrophobic fluids?

A

It is hard to transport lipids though hydrophobic fluids

Lipoproteins can get around this

36
Q

Lipoproteins

What are lipoproteins?

A

They transfer lipids
- Lipids are hydrophobic and thus are not soluble in hydrophobic fluids like blood serum, therefore they need carriers to help them transport

37
Q

Lipoproteins

How many classes of lipo proteins are there?

A

4

38
Q

Lipoproteins

How are Lipoproteins uptaken?

A

Endocytosis: LDL particles bind to receptor and become engulfed by the membrane to form an endosome

Endosome fuses with lysosome for degradation of LDL into AAs, TAG, and cholesterol

NA (6 decks)

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