Lipids Flashcards
1
Q
Lipids classification
A
Fatty acids
Vit fat soluble ( A,E,K,D)
Phospholipids
Amphipatics :
Sphingolipids
Triacylglycerol
Glycolipids
2
Q
Triacylglycerol structure
A
3 fatty acids
3
Q
Types of triacylglycerol in natural oils
A
Unsaturated FAs
4
Q
Primary target of salivary lipase
A
Fewer than 12C tTAGs
5
Q
Solid fats composed mostly of
A
Saturated fats
6
Q
Calories of fat per gram
A
9
7
Q
Functions of fats
A
Structure of cells Enzyme cofactor Vision Digestion Anti oxidant
8
Q
Daily fat consumption average
A
60-160g
9
Q
Thé 2 essential dietary fatty acid
A
Linoleic acid which gives arachidonic acid
a-linolenic acid
10
Q
Bile acid production rate limiting step
A
Cholic acid synthesis
11
Q
Bile acid synthesis pathway
A
Cholesterol to cholic acid
12
Q
Bile salts formation location
A
Liver
13
Q
Pancreatic lipase action on TGs
A
Break it down to 2-monoacylglycerol
And free fatty acids at carbon 1 and 3
14
Q
When is stored fat used ?
A
When there’s non availability or inadequacy of carbohydrates or the impossibility of metabolizing them for energy
15
Q
What hormone ca activate lipase?
A
Glucagon
Epinephrine
Nor epinephrine
16
Q
How can insulin inhibits lipase activity
A
Insulin promotes dephosphorylation of lipase by cAMP and PKA inhibition
17
Q
Acetyl coa carboxylase in fatty acid synthesis is inhibited by …
A
Hormone mediated phosphorylation so cAMP activation inhibits it
18
Q
Rate limiting step in fatty acids synthesis
A
Acetyl coa carboxylase
19
Q
How are fatty acids transported into blood
A
Serum albumin
20
Q
Fate of glycerol produced by TGs degradation
A
Goes to liver
Converted to dihydroxyacetone phosphate by glycerol kinase
21
Q
Fate of fatty acids after activation
A
Can be broken down to form CO2
Can be used to produce TGs
22
Q
Activation of fatty acids done by
A
Acyl coa synthétase
23
Q
Where does fatty acid activation occur
A
Outer mitochondrial membrane
24
Q
Product of fatty acid activation
A
Acyl Coa
25
Transport of acyl coa into mitonchondria ( less than 12c)
Passive diffusion
26
Transport of acyl coa into mitonchondria ( more than 12c)
Acyl coa converted to acyl carnitine and converted back to acyl coa once inside
Done by carnitine acyltransferase I (outer) and II (inner)
27
Disease related to carnitine synthesis , transfer ease etc causes
Muscle cramping
Severe muscle weakness especially in exercise
Death
28
Fatty acid oxidation regulation
Malonyl coa can inhibit carnitine acyl transferase I
29
Goal of fatty acid oxidation
Break down of fatty acid produce ATP
| Acetyl coa formes can enter citric cycle producing even more ATP
30
Beta oxidation pathway
Fatty acid converted to trans-enoyl -CoA by acyl Coa dehydrogenase
FADH2 PRODUCED
Trans-enoyl -coa converted to L-B-hydroxylacyl-CoA by enoyl coa hydratase
l-b-hydroxyacyl-COa converted to B-ketoacyl-CoA by B-hydroxyacyl-coa dehydrogenase
NADH PRODUCED
B-ketoacyl-CoA converted to acetyl-coa and fatty acids (less 2 carbons)
31
ATP production per cycle of fatty acid oxidation
1 NADH
1 FADH2
1 Acetyl coa which goes to citric cycle
So that’s 2.5+1.5+10= 14 ATP
32
Do you use ATP during fatty acid activation?
Yes 2 ATP
33
Goal of fatty acid oxidation in peroxisomes
Breakdown of very long fatty acids (more than 22 carbons)
34
X- adrenoleucodystrophy
Disease due to defect of ALD protein transport which lead to accumulation of long chain fatty acids because they can’t get to peroxisomes.
They destroy myelin and lead to death by 10 yo
35
Zellweger syndrome
Defect in peroxisome preventing breakdown of long chain fatty acid
Liver, kidney and muscles abnormalities
Death by 6yo
36
Products of odd chain fatty acid alpha oxidation
Proprionyl CoA
37
Fate of propionyl from odd fatty acid alpha oxidation
Peopionyl Coa converted to succinyl coA thanks to vitB12
38
Oxidation of monounsaturated fatty acid
enoyl coa isomerase convert the unsaturated fatty acid with cis configuration to trans enoyl coa
The rest of oxidation continue as usual
39
Oxidation of polyunsaturated fatty acids
2,4 dienoyl coa reductase convert the 2,4 dienoyl coa to cis enoyl coa ( monounsaturated)
Enoyl coa isomerase convert cis enoyl coa to trans enoyl coa.
Rest of oxidation continue as usual
40
Alpha oxidation location
Peroxisomes
41
Oméga oxidation
Starts at methyl group
Occurs in smooth ER for part of cyt p450 pathway
Médium chain length FAs
No energy produced
Produce dicarboxylic group which when processed by beta oxidation produce succinate and adipate
42
Precursors of fat production
Carbohydrate
| Protein
43
Location of de novo fatty acid synthesis
Cytosol
44
Fatty acid synthesis committed step
Acetyl coa converted to Malonyl coa by Acetyl coa carboxylase
45
Intermediate used to transport acetyl coa into cytosol for fatty acid synthesis
Citrate
46
Acetyl coa carboxylation step to form malonyl coa
Carboxy biotin intermediate give activated CO2 to acetyl coa to form malonyl coa
47
Fatty acid synthesis spiral
Acyl carrier protein ACP bien malonyl coa and acetyl coa
Formation of acetylACP and malonylACP
Condensation reaction
Réduction réaction
Dehydration reaction
Reduction
48
Fatty acid oxidation carrier
Coa
49
Fatty acid synthesis carrier
ACP
50
Is there bicarbonate dépendance in fatty acid synthesis
Yes - carbon dioxide donor
51
Major lipid in body
Acylglycerols
52
TGs synthesis precursors
L-glycerol 3 pi
Fatty acyl coa
53
Source of l glycerol 3 pi
Dihydroxyacetone phosphate reduced to L glycerol 3 pi
In liver only, glycerol from TGs degradation can be act on by glycerol kinase to form glycerol 3 pi
54
Reduction of dihydroxyacetone pi occurs in
Liver and adipose tissue
55
Adipocyte Only take up Glucose in the presence of insulin
True or false
True
56
Fatty acyl activation before TGs synthesis
FA activated by coa addition
Leads to fatty acyl coa synthesis
57
TGs synthesis mechanism
2 fatty acyl coa added to glycerol 3 pi at carbon 1 and 2 by glycerol phosphate acyltransferase
Gives phosphatidic acid
Phosphatidic acid hydrolyzed by phsphatidate phosphatase and gives diacylglycerol
Diacylglycerol reacts with 3rd fatty acid and gives TG Via diacylglycerol acyltransferase
58
Phospholipids structure
L glycerol 3 pi with 2 hydroxyl group estérifier to fatty acids
Last groups estérifies to phosphoric acid
59
Major classes of phospholipids
Glycerol backbone
Sphingosine backbone
60
Most abundant phospholipids in plants and animals
Phosphatidylcholine
Phosphatidylethanolamine
Phosphatidyl serine
61
Phospholipase A1 act on ..
FA at carbon 1
62
A2 phospholipase act at
FA at carbon 2 of phospholipid
63
C phospholipase act at
Before phosphate of phospholipid
64
D phospholipase act at
After phosphate of phospholipids
65
Phospholipase A2 role
Releases arachidonic acid from phosphotidylinositol to produce PG
66
2 strategies of phospholipid synthesis
Diacyglycerol formed like in TGs synthesis activated by CDP which can then be replaced on molecule by polar head group
Or
CDP already bound to head group
Head group activated transferred to diacylglycerol giving the phospholipid
67
Phosphatidylinsolitol serves as reservoir of
Arachidonic acid
68
Which one is more hydrophobic
A . Cholesterol
B. Cholesteryl ester
B
69
2 major sources of cholesterol in body
Dietary cholesterol
Cholesterol synthesized in extrahepatic tissues
De Novo synthesis from liver
70
Route for Dietary cholesterol to liver
Chylomicron remnants
71
Route for cholesterol synthesized in extraaheparic tissues to liver
HDL route
72
Major fate of cholesterol
Secretion of VLDL
cholesterol secreted in bile
Cholesterol converted to bile acids
73
Major sites of cholesterol synthesis
Liver and intestine 80%
74
Other sites of cholesterol synthesis
Adrenal cortex
Reproductive tissue LIKE OVARIES AND TESTES
75
Biosynthesis of cholesterol
(I)
2 Acetyl CoA —> acetoacetyl CoA
Enzyme : thiolase
(II)
Acetoacetyl CoA + acetyl CoA —> HMG-CoA
Enzyme : HMG
(III)
HMG CoA —> mevalonate
Enzyme : HMG-CoA reductase
NADPH used , CoA released
3 steps later , squalene is formed
Squalene gives lanosterol which gives cholesterol
76
2 forms of HMG CoA synthase isoenzymes
Cytosolic form for cholesterol synthesis
Mitochondrial form for ketone body synthesis
77
Rate limiting step in cholesterol synthesis
HMG CoA reductase
78
Is HMG CoA reductase reversible or irreversible
Irreversible
79
Regulation of HMG CoA reductase
High cholesterol inhibits enzyme
Inactive When enzyme phosphorylated
HMG COA pi —-> HMG CoA
Done by phosphatase
Phosphatase activated by insulin and inhibited by glucagon
AMP kinase can give the inactive form
80
How is cholesterol eliminated in humans
Conversion to bile acids and bile salts
81
What drugs are used in high plasma cholesterol
Statins (atorvastatin, lovastatin, simvastatin)
82
How do statins help in decreasing cholesterol level
Act as analog of HMG CoA and competitively inhibit HMG CoA reductase
83
Where are bile salts synthesized
Liver
84
Primary bile acids
Cholic acid
Chenodeoxycholic acid
85
Bile acid found in largest amount in bile
Cholic acid
86
Fate of primary bile acids
Converted to glycine or taurine
87
Lipoproteins functions
Transport of fat soluble substance
88
Type of lipoproteins
Chylomicrons
VLDL
LDL
HDL
89
Lipid part of lipoproteins
Depends on type of lipoproteins
90
Protein part of lipoproteins
Apolipoproteins
91
Lipoproteins classification
HDL (33% protein )
LDL
IDL
VLDL
Chylomicrons (1-2% proteins )
92
Functions of apoproteins
Structural Components
Enzyme cofactors
Ligands for interaction with lipoprotein receptors in tissues
93
Major apo lipoprotein in HDL
APO- A1
| also found in chylomicrons
94
Major chylomicrons apo lipoproteins
Apo-B48
95
Major LDL apo lipoproteins
Apo-B100
| also found in VLDL
96
Apo c2
Found in HDL, chylomicron’s and VLDL
| Serve as cofactor for lipoproteins lipase
97
Apo E
Found in chylomicron remnants , VLDL, IDL, HDL
Ligand used for interaction with tissue lipoprotein receptor
98
3 major pathways of lipid transport
Exogenous pathway (dietary lipids to tissues )
Endogenous pathway ( lipids from liver to tissues )
Reverse cholesterol transport pthway ( cholesterol in tissues to liver )
99
Lipids and proteins proportion in chylomicrons
High percentage of lipid
Low protein percentage
100
Chylomicrons lipid transport pathway
Exogenous lipid transport
101
Lipoprotein responsible for milky appearance of plasma after meal
Chylomicrons
102
Iipoproteins responsible for transport of cholesterol to liver
Remnants of chylomicrons
103
Chylomicron pathway
Chylomicron carry dietary fats
Chylomicron acquire apo CII and apo E from HDL
Chylomicron complex meet lipoprotein lipase and removal of TGs and chylomicrons remnants released
Chylomicron remnants transport cholesterol to liver where apo E binds receptor on liver for delivery
104
Where can you find lipoprotein lipase
Anchored to capillary wall of tissues ( adipose, cardiac, skeletal)
105
Is there LPL in liver ?
No
106
VLDL function
Transport TAGs from liver to target tissues
107
Endogenous pathway of lipid transport
B100 helps form export VLDL
VLDL get apo CII, apo E From HDL
VLDL interacts lipoprotein lipase producing LDL
LDL goes to tissue where B100 binds receptors
LDL gets into cell and deliver cholesterol
108
IDL fate
Converted to LDL
Direct uptake by liver
109
Primary carrier of cholesterol for delivery to tissues
LDL
| With highest half life
110
How is the uptake of LDL done ?
Receptor mediated endocytosis
111
Cholesterol uptake fats
Cholesterol incorporated into membrane
Repression of cholesterol synthesis
Stimulate of cholesterol storage
Repression of LDL receptor synthesis
112
Reverse cholesterol transport pathway
Nascent HDL from liver with low lipid level
HDL circulâtes in blood and picks up cholesterol
HDL goes back to liver with cholesterol
113
Functions of HDL
Reservoir of apolipoproteins necessary for other lipoproteins
Uptake of cholesterol- excellent acceptors of cholesterol
114
Enzyme responsible for estérification of free cholesterol
Lecithin cholesterol acyltransferase (LCAT)
115
What happens if Chosteryl ester present in HDL
HDL can’t get back to cell
116
How is damaged LDL called
OxLDL
117
What happens if elevated oxLDL
Increased monocytes adhésion leading to Marcel phases engulfing the oxLDL by endocytosis => form FOAM cells
118
Benefits of HDL
Absorbs most of cholesterol in extra hepatic tissues “cholesterol sponge”
Unloads CE to liver
Degrades oxLDL
119
Does increase lipoproteins especially LDL can lead to atherosclerosis?
Yes
120
Source of hormones
Cholesterol
121
Dyslipoproteinemia
Abnormal lipoproteins in blood
122
Primary dyslipoproteinemia
Hyper synthesis or hypodegradation of lipoproteins due to enzyme deficiency
123
Secondary lipoproteinemia
```
Complication of another conditions
Like :
Extrahepatic obstruction
Exogenous sex hormones (oral pill)
Steroids
Diabetes mellitus
Biliary cirrhosis
Hypothyroidism
Alcohol consumption
Obesity
Thiozide diuretics
```
124
Fredickson classification Of lipid disorders
Type I dyslipidemia
Type IIa dyslipidemia
Type IIb dyslipidemia
Type III
Type IV.
125
Type I dyslipidemia
Decreased lipoproteins lipase
Increased TGs so increased chylomicrons
Cause :
pancreatitis (TGs obstruction)
Éruptive xanthomas
Lipemia retinalis
126
Type IIa lipidemia ( familial hypercholesteremia)
Familial
Young death if homozygous ( less than 20)
LDL receptor gene defect or absent
LDL cholesterol increased
Causes :
127
Type IV familial combined hyperlipidemia
Obesity and insulin resistance common
