Zaidi: Lipids and Lipoproteins Flashcards

(100 cards)

1
Q

TG

A

Triacylglycerols

Major storage form of fatty acids

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2
Q

TG composition

A

one glycerol group and three fatty acid chains

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3
Q

Dietary TG is processed where

A

in the intestinal cells

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4
Q

De Novo TG synthesis occurs

A

in liver hepatocytes and adipocytes

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5
Q

TG Synthesis in Intestinal Cells: sequence

A

TGs are broken down in the lumen of the intestine into

1) FAs
2) 2-monoacylglycerol
Both are transported across the epithelia. Inside, FAs are converted to
1) Fatty acyl CoA
and 2-monoacylglycerol is converted into
1) Diacylglycerol.
Fatty acyl CoA and diacylglycerol are combined to produce Triacylglycerols (TGs), which are packaged with
apolipoproteins and other lipids to form CHYLOMICRONS

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6
Q

After TGs are reassembled in the intestinal cell, what happens

A

they are combined with apoproteins and lipids = chylomicrons

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7
Q

In the liver, there are a number of events leading to TG synthesis: what are the “big” initial steps

A

Glucose is converted into DHAP, which is reduced and combined with an oxidized form of glycerol to form Glycerol-3-P.

G3P is combined with fatty acyl CoA to form a number of intermediates, eventually TG

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8
Q

fatty acyl coA is responsible for

A

activating fatty acids that have been transported from the lumen into fatty acyl CoA inside the cell

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9
Q

Glucose is converted into G3P by

A

G3P Dehydrogenase

Hepatocyes

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10
Q

Glycerol is converted into ___ by _____

A

Glycerol 3P by Glycerol Kinase

Hepatocytes

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11
Q

In the liver, de novo FAs are initially

A

converted into FA-CoA by FA-CoA Synthase, eventually combined with G3P, and subsequently comverted into TG and repackaged into chylomicrons

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12
Q

TG synthesis in adipocytes: what two processes occur before production of a TG happens?

A

Glucose is broken down via glucose and transformed into G3P.

FA is broken down into FA-CoA

G3P and FA-Coa are combined to eventually form TG and stored

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13
Q

What enzyme activates FA into FA-CoA?

A

FA-CoA Synthase

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14
Q

VLDL is produced in the

A

hepatocyte and released into the blood

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15
Q

Capillary Lipoprotein Lipase

A

Chylomicrons and LDLP are delivered to the adipocyte.

CLPL break these down into FA’s

found in the adipocyte:

breaks down lipoproteins and VLDL to form glycerol and FAs. these are internalized and used for TG formation

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16
Q

In which cell is glucose converted to glycerol by Glycerol kinase?

A

Hepatocyte. Does not happen in the adipose cell, which uses glycolysis followed by G3P Dehydrogenase to produce Glycerol-3-P

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17
Q

which enzyme is used by hepatocytes to form glycerol but not in adipocytes?

A

glycerol kinase

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18
Q

What is the source of glycerol in the hepatocyte

A

it’s moving around freely because of the breakdown of TG but also because of glycolysis

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19
Q

where is glycerol kinase found?

A

the liver only

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20
Q

CLPL

A

made by adipocyte but RELEASED out of the adipocyte

breaks down VLDL and chylomicrons into the FAs, which are then used to form TGs inside the cell

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21
Q

where is the source of glycerol in adipocyte?

A

glycolysis, but lacks the glycerol kinase

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22
Q

Insulin acts on which enzyme in the adipocyte?

A

capillary lipoprotein lipase

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23
Q

What does Insulin mobilize in adipocytes?

A

the breakdown of VLDL and chylomicrons by capillary lipoprotein lipase

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24
Q

TG are broken down where

A

adipocytes

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25
why don't hepatocytes or intestinal cells break down TG?
they deliver TGs to different locations, but its hepatocytes that are primarily responsible for breaking down the TGs
26
What three enzymes do we find in the adipocyte involved in TG breakdown (just name them)
hormone sensitive lipase lipoprotein lipase monoacyl-glycerol lipase
27
hormone sensitive lipase is activated ( -/+) by
norepinephrine and epinephrine and glucagon (+) | insulin (-)
28
hormone sensitive lipase does what?
mobilizes TGs into FA and DAG
29
Lipoprotein Lipase is found where and does what
adipocyte | converts DAG into an FA and a monoacylglycerol
30
monoacyl-glycerol lipase does what
converts monoacyl glycerol into FA and glycerol
31
FAs in the adipocyte leave according to size
shorts FAs are soluble and diffuse out, long FAs are combined with albumin to exit
32
HSL is activated directly by
Hormone Sensitive Lipase is activated by phosphorylation by PKA
33
PKA does what
"ultimately" activates HSL is activated by hormones via cAMP (GCPR) signaling cascade it phosphorylates Hormone Sensitive Lipase (HSL) to initiate TG breakdown
34
Hormone Sensitive Lipase is inactivated by
Protein Phosphatase 1 (DP1)
35
How does DP1 act in the cell?
it is INACTIVATED by insulin
36
Epinephrine and Glucagon promote
lipolysis
37
Insulin inhibits
lipolysis
38
Glucaon is released in response to
hunger
39
Epinephrine is released in response to
exercise
40
Insulin is released in response to
high carb meal
41
Perilipin
family of proteins that coats lipids in adipocytes and muscle cells REGULATED BY PKA regulates LIPOLYSIS by blocking physical access to HSL overexpression leads to inhibition of lipolysis and knock out the revers effect target of anti-obesity drugs
42
what does perilipin do exactly? who controls it?
it blocks physical access HSL PKA
43
Perilipin coats
lipid droplets and prevents HSL from activating their degradation
44
Synthetic FATs
Olestra
45
what are synthetic fats made from?
synthetic fats made of sucrose backbone with 6-8 fatty acids no absorbed in small intestine no calories excreted out in stool absorb vitamins A, D, E, K high amounts of olestra cause deficiency in these vitamins abdominal cramps, bloating and diarrhea
46
Olestra
synthetic fatty acid that humans lack an enzyme to breakdown absorbs K.A.D.E, so depletes you of vitamins causes bloating, diarrhea etc sucrose with a backbone of 6-8 fatty acids
47
Lipoproteins serve what purposes,
transport form for TG, cholesterol, and fat soluble vitamins
48
Structure of the lipid: outershell and inner shell
outer: monolayer of phospholipids, free cholesterol, apoproteins inner hydrophobic TGs, cholesterol esters
49
ACAT
Acyl CoA Acyl Transferase (ACAT)
50
ACAT
Transfers acyl groups to cholesterol to make them hydrophobic (cholesterol ---> cholesterol-estor) cholesterol ester
51
5 different types of lipoproteins
1. chylomicron 2. VLDL 3. IDL 4. LDL 5. HDL
52
Chylomicrons
largest and least dense of the lipoproteins High TG content ApoB-48 and ApoC-II and ApoE
53
What the three surface apoproteins associated with chylomicrons?
ApoB-48 Apo-E Apo-C-II exogenous, formed from dietary fats
54
VLDL
ApoB-100 ApoE ApoC-II
55
IDL
ApoB-100 | ApoE
56
LDL
ApoB-100
57
HDL properties
smallest, most dense, high protein and phospholipid content
58
swelling in LNs found in infections and cancer
non-Hodgkin lymphoma
59
Apolipoprotein functions
Structural, Transport, Cofactors for Enzymes
60
Apolipoproteins function: structural
stabilizes lipoproteins
61
Apolipoproteins function: transport
redistribution of lipids between tissues
62
Apolipoproteins finction: coenzymes
Apo-CII activates LPL
63
Type I Hyperchylomicronemia
AKA hyperchylomicronemia Deficiency in Apo-C-II OR defective lipoprotein lipase the effect is to elevate chylomicrons and TGs inability to hydrolyze TAGs, chylomicrons, VLDL
64
When is Type I Hyperchylomicronemia diagnosable?
Primary LPL deficiency in infancy | ApoC-II deficiency, post adolescence
65
What is a treatment for Type I Hyperlipoprotenemia?
low fat diet
66
Clinical symptoms of type I hyperlipoprotenemia
abdominal pain, acute pancreatitis
67
Type II hyperlipoproteinemia
AKA familial hyperchylomicronemia (FH)
68
Type II hyperlipoproteinemia: Cause
defects in LDL uptake via LDL receptor
69
Type II hyperlipoproteinemia: what is impaired?
LDL receptor fails to recognize ApoB 100 on LDL
70
Type II hyperlipoproteinemia: long term problems
LDL adding to athersclerosis
71
Type II hyperlipoproteinemia: genetics
autosomal dominant inheritance
72
Normal cholesterol is
130-200 mg/dl
73
cholesterol for heterozygous Type II hyperlipoproteinemia is
300-500 mg/dl
74
homozygous for Type II hyperlipoproteinemia is
>800 mg/dl
75
untreated homozygous die from
coronary heart disease CAD befroe teenager years
76
untreated homozygous develop CAD by
age 40
77
Two sources of G3P in the liver
when glycerol kinase phosphorylates glycerol or when DHAP is reduced
78
insulin stimulates adipocytes to secrete
capillary lipoprotein lipase, which recognizes ApoC-II in chylomicrons and VLDL
79
PKA is activated by ___ which allows the PKA to do what?
glucagon, phosphorylate HSL
80
Protein Phosphatase 1 does what?
it dephosphorylates HSL
81
PP1 is activated by
insulin
82
Good Cholesterol: content and Apos
high protein and phospholipid content ApoA-I ApoE ApoC-II
83
Chylomicron processing
1. nascent chylomicrons are synthesized in the liver and transported via lymphatics to the bloodstream 2. mature chylomicron is produced when HDL adds ApoC -II and ApoE 3. Chylomicron ApoC-II is recognized by CLPL, which hydrolyzes TGs into glycerol and FAs: ApoC is released back to HDL 4. FAs and glycerol are endocytosed by binding ApoE
84
abetalipoproteinemia
lack of ApoB's
85
VLDL, IDL, LDL prcoessing
1. VLDL is released by the liver. ApoCII is recognized by CLPL, breaks down VLDL. ApoCII released back to HDL. 2. The remaining molecule is IDL. Cholesterol in the IDL is released via the receptor recognition of ApoE. 3. IDL loses more TGs and via hepatic lipoprotein lipase s well as ApoE ---> becomes LDL 4. LDL delivers cholesterol to the liver and peripheral tissues via binding of ApoB-100 to LDL receptors on targets cells etc.
86
HDL processing
1. HDL is produced in the liver 2. it is released and picks up cholesterol from tissues 3. is esterfies cholesterol 4. it exchanges estrified cholesterol with VLDL, IDL, LDL for TGs and phospholipids 5. it exchanges and receives ApoE and ApoC-II with VLDL, IDL, LDL 6. VLDL, IDL, LDL deliver cholesterol to liver
87
Type I Hyperlipoproteinemia Cause, Effect
Deficiency in ApoC or LPLs | Surge of TGs and Chylomicrons
88
Type II Hyperlipoproteinemia Cause Effect
Deficiency in LDL receptor | Surge in Cholesterol, TGs, LDL, VLDL
89
Type III hyperlipoproteinemia
AKA familial dysbetalipoproteinemia Defect in ApoE Surge in cholesterol, Chylomicon remnants, TGs, IDL
90
Type IV hyperlipoproteinemia
aka familial hypertriglyceridemia Reduction in catabolism of VLDLs or increase in their synthesis Surge in cholesterols (slightly), TGs, VLDL
91
Type V hyperlipoproteinemia
combination of I and IV surge in chylomicrons, VLDL, TGs but normal LDL
92
Tangier disease
defect in transporter that supports cholesterol pickup by nascent HDL
93
abetalipoprotenmia
Lack of ApoB's decrease in chylomicrons and VLDL, IDL, LDL
94
hpoalphaliporproteinemia
accelerated catabolism of ApoA I an II | decrease in HDL
95
HDL's beneficial effects
because of its ability to receive cholesterol from peripheral tissues, HDL increase is considered to confer benefits like reduced CAD. HDL is increased by exercise, smoking cessation, moderate alcohol consumption, and antihyercholestermic drugs and weight loss
96
HDL levels are low in
smoking, progestin, androgens, beta blockers, and high intake of PUFA (omega-6)
97
Statins
statins mimic the structure of HMG CoA and Mevalonate (substrate and product of HMG Co-A Reductase
98
HMG CoA Reductase
rate limiting enzyme in cholesterol biosynthesis Statins are competitive inhibitors of HMG CoA Reductase enhance transcription of LDL receptor more uptake into hepatocytes, lowering plasma levels w
99
Lovastatin
targets HMG CoA Reductase
100
what is the rate limiting step in cholesterol biosynthesis?
HMG-CoA reductase converting HMG-CoA along with NADPH reducing HMG-CoA into Mevalonic Acid. Mev is eventually converted into cholesterol