Valencik Lipid Metabolism Flashcards
1
Q
What are the four pathways of lipid transport?
A
1) Food → Any Tissue
2) Liver → Other Tissues
3)Other Tissues → Liver
(reverse transport)
4)Adipose Tissue → Other Tissues
2
Q
(blank) levels are higher than blood glucose and vary with dietary intake.
A
plasma lipid
3
Q
What do free fatty acids look like?
A
R-COOH
4
Q
Where do we find FFAs and how do they work?
A
stored in adipose-> mobilized to provide energy to other tissues-> travel in blood and NONCOVALENTLY attached to alubmin
5
Q
What do we need to do with TAGs and what are the two types?
A
we need to either store them or use them
dietary and synthesized
6
Q
Where do we get cholesterol?
A
we get it from our diet
made by most tissues
7
Q
What is the storage form of cholesterol?
A
cholesterol esters (CE)
8
Q
(blank) are lipids with a hydrophilic phosphate head group.
A
phospholipids
9
Q
(blank) are the mode of transport for lipids.
A
lipoproteins
10
Q
What are macromolecular assemblies of protein and lipid aggregates?
A
lipoproteins
11
Q
What is the protein component of a lipoprotein called and what is special about this?
A
an apolipoprotein
It is amphipathic
12
Q
What can the lipid component of a lipoprotein be?
A
TAG, FFA, cholesterol, cholesterol esters, phospholipids, other lipids and their derivatives
13
Q
Which of these are hydrophobic: TAGs Cholesterol esters Free cholesterol Phospholipid
A
TAGs
cholesterol esters
14
Q
Plamsa liporpteins can be separated by (blank).
The more lipids the (blank) the lipoprotein.
A
electrophoresis
lighter
15
Q
When doing electrophoresis, which kinds of lipoproteins wouldnt really move?
What lipoproteins would move very far?
A
heavy, large lipoproteins with mostly nonpolar lipids such as chylomicrons
alpha-lipoproteins (HDL)
16
Q
Put these lipoproteins in order form biggest to smallest.
HDL, VLDL, LDL, Chylomicrons
A
Chylomicrons, VLDL, LDL, HDL
17
Q
What are these the normal ranges for (mg/dL): 400-800 40-280 120-280 65-200 30-90 125-275 8-25
A
TOtal lipid: 400-800 Triglycerides: 40-280 Total cholesterol: 120-280 LDL: 65-200 HDL: 30-90 Phospholipids: 125-275 FFAs: 8-25
18
Q
What makes up 70% of plasma cholesterol
A
LDL cholesterol
19
Q
What is always bound to albumin?
A
FFAs
20
Q
What all does total cholesterol include?
A
both cholesterol and cholesterol esters
21
Q
Where do you find the majority of triglycerides?
A
in VLDLs
22
Q
Where do we make chylomicrons and what percentage of chylomicrons are made up of TAGs?
A
Intestine
86% (contains the highest amount of TAGs)
23
Q
Where do we make LDL and what percentage is made up of cholesterol esters and cholesterol?
A
From VLDL and IDL
40% cholesterol esters and 8% cholesterol
24
Q
What has the highest fraction of total cholesterol?
A
LDLs
25
When fasting, where are the most TAGs found?
in VLDLs
26
When fasting, where is the most cholesterol found (C + CE)?
LDL
27
Digestion and absorption of dietary lipids occur in the (blank).
small intestine
28
Once you get micelles into the small intestine, what degrades triglycerides?
intestinal lipases
29
When you have TAGs in the small intestine, what do they combine with and what do they become?
combine with cholesterol and apolipoproteins into chylomicrons
30
Chlyomicrons move through the (blank) and bloodstream to tissues.
lymphatic system
31
What converts TAGs to fatty acids and glycerol?
lipoprotain lipase (activated by ApoC-II) in the capillary
32
Once you have your broken down TAGs into glycerol and fatty acids where do they go?
enter cells where they can be oxidizes as fuel or reesterified for storage
33
Digestion and absorption of dietary lipids occur in the small intestine, after reassembly in the enterocytes the TAGs are packaged into (blank) and delivered to (blank and blank) tissues (primarily).
chylomicrons
| muscle and adipose
34
(Blank) are not used by the brain or liver (they dont have LPL (lipoprotein lipase))
chylomicrons
35
Do fatty acids and glycerol get taken up by the lactating mammary, spleen, lungs, kidney, endocrine glands and aorta?
yes
36
dietary triglycerides undergo variable degrees of (blank) in the intestinal lumen.
hydrolysis
37
Medium and short fatty acids are absorbed as such into the (Blank)
portal blood
38
Free fatty acids are activated by (blank) prior to TAG assembly.
acyl-CoA synthetase
39
Long-chain fatty acids are reassembled into (Blank) in the ER then incorporated into chylomicrons.
TAGs
40
What happens to Long-chain fatty acids?
turns into TAGS and put into chylomicron
41
Do enterocytes possess glycerol kinase, what does this mean for enterocytes?
no
This means they cannot they cannot metabolize the glycerol produced during triacyl glycerol degradation. This glycerol is instead shuttled to the liver
42
What is the life span of chylomicrons in the plasma? What is the life span of TAGs?
less than 1 hour
| 5-10min
43
Where do we find B-48?
only on chylomicrons!!!
44
TAGs are reassembled and chylomicrons are formed in the (blank) of the intestinal mucosa
endoplasmic reticulum
45
What are the three roles of apolipoproteins?
1) regulate plasma lipid metabolizing enzymes
2) facilitate lipid transfer
3) mediate endocytosis
46
Explain the journey that TAGs take?
Tags get reassembled in enterocytes->put into chlymicrons->chylomicrons enter lymphatic system-> chylomicrons transport TAGS and Cholesterol to rest of the body
47
Apolipoproteins have are hydrophobic or hydrophilic?
amphipathic actually
48
What are these:
| apoB-48 and apoA-I, -A-II and IV.
apolipoproteins
49
Once chylomicrons enter the blood, what do they need and where do they get it from?
they need apoC-11 and apoE from plasma HDLs
50
How do we get the TAGs out of the chylomicrons?
lipoprotein lipase (LPL)
51
What is lipoprotein lipase (LPL) activity dependent on?
apoC-II
52
During TAG hydrolysis done by LPL, what apolipoproteins peel off the surface of the chylomicron and where do they go?
A and C
| transferred to HDL
53
You cant just place the apolipoproteins from the chylomicrons to HDL, instead you need a special protein which is.......?
phospholipid transfer protein
54
SO you have a chylomicron, it gets its TAGs ripped out by LPL and then all the A and C apolipoproteins fall off..... now what happens to your chylomicron, does it keep getting beat up by LPL or does it finally get to relax?
since apoC is what activated LPL, and it just fell off, LPL can no longer beat up the chylomicron
55
Where do we find LPL? Where do we have no LPL?
Have: skeletal, cardiac, adipocytes
| Don't Have: liver, brain
56
Food consumption increases (blank) on adipocytes but decreases this expression on skeletal and cardiac muscle. Why is this important.
LPL
| ensures that dietary fat is stored in well-fed state but will be used by cardiac and skeletal muscle during fasting.
57
(blank) detaches from LPL from the capillary membrane
heparin
58
THe chylomicron remnant that has been stripped of A and C apoplipoproteins and TAGS, what is left in it?
cholesterol esters, apoE and apoB-48 and left over TAGS
59
What happens to the chylomicron remnant?
The apo E on the chylomicron gets bound by an Apo E dependent receptor that drags the whole thing to lysozomes for degradation in the liver
60
Overall, dietary cholesterol ends up in the (Blank)
liver
61
(blank) function to deliver dietary triglycerides to adipose tissue and muscle and dietary cholesterol to the liver.
chylomicrons
62
What are these:
```
C→ free cholesterol
CE→ cholesterol ester
HDL→ high-density lipoprotein
LPL→ lipoprotein lipase
PL→ phospholipid
TG→ triglyceride
```
things that interact with chylomicrons
63
In the liver, excess carbs and fats are used to synthesize (Blank and blank)
TAGs and lipids
64
In the liver, TAGs, lipids and cholesterol are packaged into (blank) by the ER and golgi.
VLDLs
65
VLDLs are (blank) into the blood circulation for delivery to extra-hepatic tissues.
exocytosed directly
66
Explain the process of creating and transporting TAGs in the liver?
carbs and fats are turned into TAGS-> TAGs, lipids and cholesterol are packaged into VLDLs by ER and Golgi-> VLDLs are exoctyosed into blood for delivery to other tissues-> free fatty acids from TAGs are eventually used for beta oxidation
67
In liver, you package cholesterol,lipids and TAGs into VLDLs, what do these VLDLs quickly obtain after being formed?
apoCs and ApoEs and additional cholesterol esters from HDL
68
How long is the lifespan of a VLDL?
less than an hour
69
What is the very large Apo stuck to a VLDL?
apoB-100
70
What are all the components of the VLDL?
ApoB-100 plus ~ 7% cholesterol, 13% cholesterol esters, 55% TAG and 18% phospholipids and ApoCs and ApoEs
71
ApoB-48, which is found in chylomicrons and ApoB-100 found in VLDL come from the same (blank). How is this done?
gene
In fact, apoB-100 is made up of all the AAs that apoB-48 has and more.
Through tissue-specific RNA editing
72
Is there any proteolytic processing involved in the difference betwee apoB-48 and ApoB-100?
NOOOOOOOOO!!!!
| It is done through tissue-specific RNA editing
73
Apo 48 and Apo 100 are synthesized from the same gene. Apo 100 is synethesized from the entire gene, where apo48 is only synthesized from half the gene. How do make sure only half the gene gets translated to make apo48?
In the intestine (where chylomicrons are made), the RNA is post-transcriptionally altered to contain a STOP codon at position 2180 (CAA → UAA).
74
VLDL travels a path similiar to chylomicrons but hydrolysis is (blank)
slower
75
How do we get TAGs out of VLDL?
using extra-hepatic LPL (remember liver doesnt have this)-> so we can send FFAs into tissue
76
When you have VLDLs and LPL what happens to your apos?
VLDL loses ApoCs to HDL
77
When you degrade VLDLs via LPL what does VLDL turn into?
it turns into IDL (intermediate-density-liproprotein)
78
VLDLs acquire more (blank) from HDLs through the enzymatic activity of cholesterol ester transfer protein (CETP).
cholesterol esters
79
VLDLs acquire more cholesterol esters from HDLs through the enzymatic activity of (blank)
cholesterol ester transfer protein (CETP).
80
What is left in the VLDL remnant?
apoB-100, Cholesterol Esters, phospholipids, some TAG and cholesterol and apoE
81
What are the 2 VLDL "remnants"
Large ones that contain lots of apoE
| Smaller ones that become IDL
82
What happens to the Large VLDL remnants?
they get endocytosed by liver
83
What happens to smaller VLDL remnants?
they turn into IDLs and then become LDLs
84
Hepatocytes have something special to breakdown IDLs and HDLs, what is this? What does it do?
hepatic lipase
| Hydrolizes TAGs and phospholipids and convertes IDL to LDL
85
What converts IDL to LDL?
hepatic lipase
86
HOw is hepatic lipase anchored to hepatocytes?
via heparin sensitive attachment (heparan sulfate proteoglycan)
87
Hepatic lipase only works on (blank) and (Blank)
IDLs and HDLs
88
LDLs are made up of 40% of (blank) and 20% (blank) and carry only apo(blank)
cholesterol esters
phospholipids
ApoB100
89
What is the lifespan of an LDL?
3 days
90
Where do most LDLs go?
2/3rds goes to the liver
91
How does the extrahepatic tissues get LDL?
via receptor mediated endocytosis and Apo B100 dependent binding to LDL receptor
92
Once LDL gets taken up by the tissues, where does it go?
to a lysozyme where the apos degrades and cholesterol esters get changed into cholesterol and put into ER or PM
93
What 2 things increase the binding of LDLs to liver cells? What inhibits the binding of LDLs to liver cells?
insulin and tri-iodthyronine (T3)
| Glucocorticoids (dexamethasone)
94
What is the primary way extrahepatic tissues get cholesterol?
from the breakdown of LDL within the hepatic cells
95
In extra-hepatic cells, excess intracellular cholesterol induces (blank) to create cholesterol esters for storage.
ACAT (acyl-CoA-cholesterol acyl transferase)
96
In extra-hepatic cells, excess intracellular cholesterol will repress transcription of (blank) and (blank)
HMG CoA reductase
| LDL receptors
97
What does SREBP (sterol response element binding protein) do?
activates transcription of LDL receptor gene
98
Are all LDLs cleared by the LDL receptor?
no
99
If not all LDLs are cleared by the LDL receptor, what happens to the rest of them?
scavenger receptors will get them only if they are old LDLs which are oxidized or acetylated
100
How can you tell if an LDL is aged/old?
it will be acetylated or oxidized
101
Where do you find scavenger receptors?
on macrophages and endothelial cells
102
What two major organs that contain many macrophages with scavenger receptors that endocytose LDLs?
spleen and intestines
103
What is the predominant way that lipids are transported from other tissues to the liver?
Where do we get the lipids and what is this transport mediated by?
ApoE mediated endocytosis of remnant particles containing cholesterol esters.
obtained from HDLs, mediated by CETP
104
Where do we usually get CE's?
HDLs
105
What are the three ways we can transport lipids from other tissues to the liver?
1) via ApoE
2) CE from HDL directly via SR-BI (scavenger receptor class B type I)
3) large HDLs with ApoEs are endocytosed
106
Nascent HDLs are released from (blank and blank) rich in phospholipids
liver and intestine
107
Nascent HDLs are released from liver and intestine (small and disc-shaped) rich in (blank)
phospholipids.
108
Nascent HDLs are very different then old HDLs, in that nascent HDLs do not have what? When do they get these?
choelsterol or cholesterol esters
| over time they accumulate these and are converted to HDL3 and HDL2
109
HDLs made in the liver are different that in the intestine due to the presence of specific Apos. Tell me which ones
When made by the liver they carry and supply:
apoA-I, apoA-II, apoC-I, apoC-II and apoE.
When made in intestine they only have apoA-I.
110
What are the biggest HDls?
HDL2
111
Nacent HDL consists of a little piece of lipid bilayer whose edge is occupied by amphipathic helices of the apolipoproteins. The A-apolipoproteins have amphipathic & (blank) portions that are separated by short, (Blank) segments.
alpha-helical portions
| nonhelical
112
Describe a nascent HDL structurally.
small and disc shaped
filled with phospholipids
surrounded by A-apoliprotein with alpha helixes and non helixes
113
The (blank) have amphipathic & alpha-helical portions that are separated by short, nonhelical segments.
A-apolipoproteins
114
How does HDL travel to tissues and what does it do there?
it binds via apoA-I or apoE, hooks up with ABCA1 (ATP-binding cassette protein-1) in cell membrane and gets pumped full of cholesterol from cell surface
115
WHen HDL comes into cells and steals all their old cholesterol, how does the cell make more?
Stored intracellular cholesterol esters will be mobilized to replace the “aged” cholesterol removed from the plasma membrane.
116
HDL particles dock to the cell surface through (blank or blank).
apoA-I or apoE binding
117
(blank) in the cell membrane pumps free cholesterol from the cell surface into HDL.
ABCA1 (ATP-binding cassette protein-1)
118
How is cholesterol processed?
via Lecithin-cholesterol acyl-transferase (LCAT)
| and CETP
119
What does Lecithin-cholesterol acyl-transferase (LCAT) do?
it binds to HDL and gets activated by apoA-I and catalyzes esterification of cholesterol.
120
(blank) is a soluble protein synthesized by the liver.
Lecithin-cholesterol acyl-transferase (LCAT)
121
What is the reaction that Lecithin-cholesterol acyl-transferase (LCAT) catalyzes?
cholesterol + phosphatidylcholine---> cholesterol ester + 2-lysophosphatidlcholine (lysolecithin)
122
In the reaction catalyzed by LCAT, what happens to the CEs and what happens to 2-lysophosphatidulchole?
CEs get put into HDL to make HDL3
| 2-LPC gets transferred to albumin
123
(blank) transfers a fatty acid from the C-2 position of lecithin to the C-3-OH of cholesterol.
LCAT
124
What does CETP do?
facilitates transfer of CEs from HDLs to Lipoprotein remnants or LDLs, during chylomicron (or VLDL) lipolysis by LPL
125
(blank) facilitates their transfer from HDLs to lipoprotein remnants or LDLs, during chylomicron (or VLDL) lipolysis by LPL.
Cholesterol ester transfer protein (aka. ApoD)
126
CETP is also called.....?
ApoD
127
How many ways are there to delivery cholesterol to hepatocytes?
3
128
What is this:
C and CEs are transported via VLDL/Chylomicron remnants or LDLs and endocytosed in an apoE dependent manner by hepatocytes.
What is this dependent on?
a way that cholesterol is delivered to hepatocytes.
| apoE
129
What happens when HDLs remain intact but give off C and CEs tohepatocytes via hepatic lipase and SR-BI?
cholesterol gets delivered to hepatocytes
130
How can intact HDLs delivery cholesterol to hepatocytes?
Hepatic lipase and SR-BI(scavenger receptor class B type I).
131
How can a HDL be endocytosed into a hepatocyte and does this happen often?
if it acquires enough apoE
| no it is the minor path
132
(blank) removes TAGs and phospholipids.
| HDL 2 → HDL3
hepatic lipase
133
(blank) selectively transfers CEs into hepatocytes
Scavenger receptor class B type I (SR-BI)
134
Explain the key way that cholesterol is transported to hepatocytes by peripheral tissues.
CETP facilitates transfer of CEs from HDLs to Lipoprotein remnants or LDLs from chylomicron (or VLDL) lipolysis by LPL, these then get transported back to hepatocytes
135
All (blank) apolipoproteins can be exchanged with other lipoprotein classes.
HDL
136
Name that disease:
Defect->Deficiency in triglyceride transfer protein. Therefore, no ApoB lipoproteins are assembled (chylomicrons, VLDLs or LDLs).
Comment->rare; severe fat malabsorption, steatorrhea and TAG accumulation in intestinal mucosa and liver.
Abetalipoproteinemia
137
Name that disease:
Absence of ABCA1 protein. Therefore apoAs can’t acquire lipids and mature HDLs don’t form.
Deposit cholesterol esters in reticuloendothelial cells, bone marrow and Schwann cells. Tonsils-”Orange”. CVD
Tangier diease
138
Name that diesase:
Absence of ApoCIII (a LPL inhibitor)
Amish, Ashkenazi Jews and 25% of centenarians. Decreased plasma TAGs and LDLs and increased HDLs.
Apo CIII defiicney
139
Name that disease:
Cholesterol esters cannot be transferred to other remnants.
Benign condition. LDL is normal to low but HDL is elevated and CE get to the liver via HDL’s.
CETP deficiency
140
The orange color of the tonsils in tangier disease is caused by dietary (blank)
carotene
141
If you have a CETP mutation or utilize a CETP inhibitor,will this protect against coronary heart disease?
nope
142
(blank) Causes a reduction in plasma C and TAG of 75-80%. Makes it very hard for fat soluble vitamins such as Vitamin E to be available to body tissues.
abetalipoproteinemia
143
What apoliporoteins does the liver make?
```
the A's
B100
Cs
D
E
```
144
What apolipoproteins does the intestine make?
A's (liver does too)
| B48
145
What is the heaviest apolipoprotein?
B100
146
What are these:
Major structural proteins of HDL, also in chylomicrons; apo A-I activates LCAT
What are they hooked up with?
apolipoprotein A's
| HDL and chylomicrons
147
What is the structural protein of chylomicrons?
B48
148
What is the structural protein of VLDL, IDL, and LDL; only apolipoprotein of LDL; mediates tissue uptake of LDL?
What is this hooked up with?
B100
| VLDL, LDL
149
These are readily transferred between different classes and (blank) activates extrahepatic lipoprotein lipase (LPL) and (blank) inhibits LPL
CII
| CIII
150
Where do we find D apolipoprotein?
on HDL
151
What mediates the uptake of the chylomicron remnants and IDL by the liver?
Where do we find it?
apoE
| VLDL, IDL, chylomicrons
152
Only “(blank)” apolipoproteins don’t get transferred around
B
153
How do lipids travel from adipose tissue to other tissues?
FAs are released by lipolysis of TAG and pass into bloodstream. These are used to produce energy in other tissues (in muscle, for example), and the remainder are used for resynthesis of TAG. There is quite a bit of futile cycling.
154
What is the component needed for FAs to become TAGs?
G3P from the breakdown of glycerol
155
What enzymes are involved in glycerolneogenesis in the liver and adipose tissue?
Pyruvate carboxylase
Malate dehydrogenase
PEPCK
Glycerol 3-phosphate dehydrogenase
156
What does PEP carboxykinase do?
turns oxaloacetate into PEP
157
PEP carboxykinase activity is induced by (blank)
thiazolidinediones (class of diabetic drugs)
158
glycerolneogenesis uses enzymes from (blank)
gluconeogenesis
159
In mice if you increase expression of (blank) mice become obese.
PEPCK
160
What is the rate limiting step of mobilization of TAGs in adipocytes?
HSL
161
What is and what does ATGL lipase do?
it is highly specific for TAG and is first step in TAG hydrolysis, creates DAG and FAs
162
What leaves the intestine?
| What leaves the liver?
chylomicrons
| VLDL
163
What enters the capillary and what leaves the capillary and how?
chylomicrons and VLDL
FFAs, remants of VLDL (IDL), LDL and chylomicrons
via lipoprotein lipase
164
What do extrahepatic tissues take up and what do they release?
HDL precursors and LDL
| HDL
165
What all does the liver absorb?
chylomicron remnants, VLDL remnants (IDL), LDL, HDL
166
Explain how adipose tissue mobilizes its tags.
adrenergic stimulus and ANP activate cAMP and cGMP which utilize protein kinases to activate ATgL and HSL which initiates lipolysis
