Dr. Koroly - Lipids Flashcards

1
Q

Why are lipids good storage molecules?

A

They are nonpolar, stored without water and chemically inert.

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2
Q

What is the overall reaction of mobilizing fatty acids from adipose tissue?

A

Triacylglycerol + H2O —> (3 lipases) —> glycerol + 3 FA’s

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3
Q

What kind of rxn is used to break up triacylglycerol to FA’s and glycerol.

A

Hydrolysis

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4
Q

What hormones bind to adipose tissue to mobilize FA’s release?

A

Glucagon and epinephrine

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5
Q

What kind of receptor protein does glucagon bind to?

A

G-Protein Receptor

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6
Q

When you want to release energy do you phosphorylate or dephosphorylate?

A

Relase Energy = add Pi

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7
Q

When you want to store energy do you remove or add Pi?

A

Storge energy = remove Pi.

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8
Q

Is Tryacylglyceride Lipase phosphorylated or dephosphorylated to activate it?

A

Phosphorylated.

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9
Q

Where is the process of TAG breakdown to FA’s and glycerol?

A

It is done in the cytosol

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10
Q

Adenylate Cyclase + ATP –>

A

cAMP

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11
Q

How is PKA activate?

A

Binding of 4 cAMP to the regulatory subunits and releases the catalytic subunits.

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12
Q

How is PKA turned off?

A

cAMP is degraded over time and PKA is deactivate.

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13
Q

What does triacylglycerol lipase do?

A

Hydrolysis of TAGs –> 3 FA’s and Glyceryol

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14
Q

What happens to glycerol released from the first steps of FA’s mobilization?

A

It is shuttled into the liver in the blood where it is turned into the intermediates of glycolysis and gluconeogenesis.

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15
Q

Once FA is moved into the cytosol of the target cell what happens.

A

It needs to be activate which is the addition of CoA via the enzyme Acyl-CoA synthase. This creates FA-Acyl-CoA.

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16
Q

What is the cost of Fatty-Acyl-CoA?

A

2 ATP

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17
Q

Where does the oxidation of Fatty-Acyl-Coa take place?

A

Mitochondria

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18
Q

How does fatty-acyl-CoA get into the mitochondria?

A

The CAT1 / CAT2 shuttle. CAT1 shuttles the fatty-acyl-carnitine into the mitochondria where it is formed back into fatty-acyl-coa and the carnitine is shuttled back out via the CAT2 enzyme.

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19
Q

What are the steps in the oxidation of fatty-acyl-coa?

A

Oxidation: via Acyl-CoA Dehydrogenase = FADH2

Hydrolysis: Add H2O

Oxidation: = NADH

Thiolysis: Add CoA

This removes 2 carbons from the 16:0

We get 1 NADH (3 ATP) and 1 FADH (2 ATP) = 5ATP

We do this 7 times and also get 8 Acetyl-CoA

(7x5) + (8x12) = 131 -2ATP = 129 NET ATP

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20
Q

How is oxidation of FA’s regulates?

A

regulation of triacylglycerol lipase - hormone sensative

CAT1 = responsble shuttling fatty-acyl-carnatine into the mitochondria.

substrate concentrations of NAD+ and Acetyl-CoA

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21
Q

When acetyl-coa is high and there is no OAA to make citrate what happens to the acetyl-coa.

A

It is condensed (2 acetyl-coa) creates acetoacetyl-coa is turned into HMG-CoA and then acetoacetate (ketone body) is shuttled to tissue that needs energy, This is then turned into the intermediates of the TCA.

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22
Q

Where is pyrivate converted to citrate when the glucose levels in the blood are high?

A

It is converted in the mitochondria of the liver.

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23
Q

Once you have created citrate in the mitochondria from OAA and Acetyl-CoA how do we get it into the cytoplasm for FA synth?

A

It goes through the acetyl group shuttle

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24
Q

Once citrate is in the cytoplasm what happens?

A

Citrate lyase is used to split citrate back into OAA and acetyl-CoA

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25
Q

What happens to the OAA and Acetyl-CoA after being split up in the cytoplasm?

A

The OAA is turned into malate –> pyruvate. In this process we make NADPH and burn an NADH. This is returned to mitochondria via the PDC.

The Acetyl-CoA + Malonyl-CoA + ATP = FA’s

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26
Q

What enzyme is repsonsible for for creation of FA from Acetyl-CoA and Malonyl?

A

Acetyl-CoA Carboxylase

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27
Q

How is Acetyl-CoA Carboxylase regulated?

A
  • Citrate turns it up
  • 16:0 turns it down
  • Response to glucagon and insulin
  • Requires biotin
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28
Q

What is the site of FA synthesis?

A

Cytoplasm in the liver cells.

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29
Q

FA synthesis happens on what enzyme?

A

A huge dimer that has seven active sites call Fatty Acid Synthase.

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30
Q

Once the 16-ACP is hanging off the fatty acid synthase what happens?

A
  1. We turn it into 16:0 via a thioesterase
  2. We activate it with a CoA
  3. Other enzymes modify the 16:0-CoA
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31
Q

How is Fatty Acid Synthase regulated?

A

Excessive sugar resulting in more acetyl-coa and citrate.

  • Citrate turns up citrate lyase
  • Acetyl-CoA turns up Acetyl-CoA Carboxylase
  • Malonyl-CoA turns down citrate lyase
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32
Q

In the process of making TAG phosphatidic acid is an intermediate - what is that used for.

A

Phosphatidic acid is pulled off for the production of membrane components. These are made first when needed before TAG are made.

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33
Q

Acetyl-CoA is being condensed into what before HMG-CoA

A

2 Acetyl-CoA –>Acetoacetyl-CoA–> HMG-CoA

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34
Q

Where does cholesterol synthesis occur?

A

Mitochondria

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35
Q

Where is ketone body production occur?

A

Mitochondria

36
Q

HMG-CoA –> Enzyme? –> Product?

A

HMG-CoA reductase –> Mevalonate

37
Q

What is the 30 carbon intermediate of cholesterol synth?

A

C30 - Squalene

38
Q

What are the characteristics of cholesterol synthesis?

A
  • All the carbons are from Acetyl-CoA
  • Ireversible
  • High energy usage
  • Uses a lot of NADPH
  • No net energy yield
39
Q

How is cholesterol synthesis regulated?

A
  • High intracellular cholesterol turns off HMG-CoA Reductase and turns up ACAT
  • Insulin turns up HGM-CoA Reductase
  • Glucagon turns down HMG-CoA Reductase
  • Receptor mediated endocytosis of extracellular cholesterol is turned off by high levels of intracellular cholesterol
40
Q

Where does ACAT work?

A

In the cells - it is responsible for turning up the production of cholesterol-esters when intracellular cholesterol is high.

41
Q

How does LCAT work?

A

LCAT in the plasma is responsible for the production of cholesterol esters.

42
Q

Where are bile salts being sythesized?

A

They are being made in the liver parenchyma cells.

43
Q

Where does steroid hormone degredatiion occur?

A

In the Liver.

44
Q

What is the primary organ of steroid synthesis?

A

The liver (although other glandular organs and most other cells can make it)

45
Q

What is one key difference between free cholesterol and cholesterol esters.

A

Free cholesterol has a polar head that makes it perfect for use in cell membranes. Cholesterol esters are nonpolar and form together into storage molecules.

46
Q

What does the sythesis of cholesterol require?

A

ATP, NADPH, Acetyl-CoA

47
Q

How do we get rid of cholesterol from the body?

A

It is never degraded and is excreted from the body as bile salts.

48
Q

What is the committed step of cholesterol synthesis?

A

The step that uses HMG-CoA Reductase this is the is the creation of melavonate.

49
Q

How many NADPH are used by HMG-CoA Reductase?

A

2

50
Q

How is cholesterol synthesis stimulated?

A

In the short-term by insulin

in the long-term by low cholesterol levels

51
Q

How is cholesterol inhibition regulated?

A

Glucagon and end product feedback in the short-term

By excess or high levels of cholesterol in the system in the long-term

52
Q

What are the actions of statins

A

It inhibits competitively HMG-CoA reductase

53
Q

What is ACAT?

A

It is a cytoplasmic enzyme that catalyzes conversion of cholesterol to cholesterol ester for storage in lipid droplets. This enzyme can be induced by high cholesterol levels.

54
Q

What is LCAT?

A

It is a serum enzyme (in lipoproteins, especially HDL) that catalyzes conversion of cholesterol to cholesterol ester for transport in blood.

55
Q

How do dietary lipid transported from the intestines?

A

Via chylomicrons which have ApoB-48. Chylomicrons are made in the intestinal cells and are shipped with all dietary fats, TAGS, cholesterol, polar lipids, vitamins ADEK. They leave the intestinal cell, enter the lymph and circulate in the blood.

56
Q

What do chylomicrons do with the TAGs they orginally left the intestines with?

A

They drop them off at adipose tissue.

57
Q

What is left of a chylomicrons after most of the TAGs have been dropped off?

A

You have a chylomocrins remnant which still have other dietary fats and vitamins. It also still has the ApoB-48 apoprotein.

58
Q

What happens to the remaining lipids in the chylomicron and also the lipids that the liver produces?

A

They are packaged up into VLDL and shipped out of the liver. This is called the endogenous path.

59
Q

What is the apoportein marker associated with VLDL?

A

ApoB-100 (this is part of the VLDL when it is shipped out of the liver.

60
Q

What does VLDL do with the TAGs it has after secretion from the liver?

A

It drops them off at adipose tissue.

61
Q

What is the primary Apoprotein that is on VLDL

A

ApoB-100

62
Q

Once VLDL has dropped of some of the TAG’s in adipose tissue what is it called.

A

A IDL (intermediate dense lipoprotein)

63
Q

Once a VLDL has lost most of its TAG’s what do we have?

A

We have LDL.

64
Q

What apoproteins are on IDL and LDL that are picked up by liver?

A

ApoB-100.

65
Q

What receptor on the liver is used to pick of IDL and LDL?

A

ApoB/E

66
Q

What process does the liver use to pick up left over IDL and LDL from the blood?

A

Endocytosis

67
Q

What other structures “eat” LDL and IDL from the blood?

A

Macrophages (these are the source of artherosclerotic plaques and foam cells)

68
Q

What is the only lipoprotein endocytosed by peripheral (not liver) cells in the body and how?

A

Only LDL and by the ApoB receptor.

69
Q

What is required for a baby chylomicron to become mature?

A

It has to pick up ApoC and ApoE from HDL. (HDL is the donor / carrier protein for these)

70
Q

How does a chylomicron get rid of TAG’s

A

The ApoC protein that was picked up from the HDL is docked on to lipoprotein lipase. Lipoprotein lipase is the enzyme that is bound to the inside of the cappilary lumen.

Once docked lipoprotein lipase is activated by ApoC and degrades the TAGs to 3 FA’s and glycerol.

71
Q

What happens to the FA’s and glycerol that are released from the lipoprotein lipase process?

A

This FFA’s are taken into the adipose cell (must be insulin stimulated) excess dietary glucose will be used to synthesize TAG’s

Glycerol is shipped to the liver for complex lipid synthesis.

72
Q

What happens tgive o chylomicron remnants?

A

CR give ApoC and phoshdytlcholine back to HDL and get some cholesterol ester in return. The HDL continue to circulate and the CR is endocytosed by liver. The ApoE that is still on the CR is what docks with the ApoB/E receptor on the liver.

73
Q

What is the fate of VLDL?

A
  1. Gets made in the liver and shipped with the ApoB-100 protein.
  2. Picks up ApoC/E from HDL and matures
  3. Drops of TAG’s at adipose and muscle just like chylomicrons
  4. Remaining lipoprotien is IDL and can either drop off more TAG and become LDL or be taken in to liver via ApoB/E receptor.
  5. If it becomes an LDL only the ApoB-100 remains and the ApoE is lost.
  6. The remaining LDL with some fats and vitamins has the ApoB-100 ligand that is bound to the liver via the ApoB/E receptor and endocytoced.
74
Q

What cells recognize the ApoB-100 ligand on LDL’s in the blood.

A

The LDL receptor on -liver cells and the ApoB/E receptor in the liver.

75
Q

How does cholesterol and cholesterol ester containing LDL enter cells?

A

Via endocytosis

76
Q

During endocytosis of LDL what happens?

A

The ApoB-100 receptor is recycled and the lipids are processed by liver. Cholesterol enters the free pool in the liver.

77
Q
A
78
Q

What are the actions of free cholesterol in the cell?

A

It down regulates the formation of new LDL receptors in the cell.

It down regulates the production of new cholesterol

is used in the repair of cell membranes and steroid production

Up regulates ACAT for production of cholesterol esters for storage in lipid droplets

Transfered outside the cell via the ABC1 transporter (ATP dependent)

Picked up by HDL and returned to liver.

79
Q

Where is HDL made?

A

In the liver, intestines and blood

80
Q

What are the components of baby (nascent) HDL?

A

Phosphotidylcholine, LCAT and ApoA

81
Q

What is the purpose of ApoA on HDL?

A

It “docks” with the ABC1 transporter on the cell.

82
Q

How is the free cholesterol transfered to HDL via the ABC1 transporter?

A

Along its concentration gradient.

83
Q

What is the fate of free cholesterol once in the HDL?

A

It is converted for storage into cholesterol esters via LCAT

84
Q

What are the three ways that cholesterol in HDL is transfered to liver?

A
  1. Via exchange of CE to CR and LDL for phosphtidylcholine
  2. Hepatic enzymes that attack them in the liver
  3. Aging HDL is endocytosed by liver.
85
Q
A