Lipids Flashcards
1
Q
Three hepatic receptors to which LDL may bind to return cholesterol esters back to the liver in reverse cholesterol transfer pathway
A
- LDL receptor
- HDL receptor
- Remnant receptor
2
Q
Electrophoretic pattern of Type V
A
Type I + Type IV; increased chylomicron band and pre-beta band
3
Q
(At least) two risk factors of the metabolic syndrome
A
- BMI > 25
- Family history of diabetes mellitus
- History of gestational diabetes
- Polycystic ovary syndrome
4
Q
Plasma apperance of Type III
A
Slightly cloudy to cloudy plasma
5
Q
Mechanism to maintain cholesterol balance; LDL receptors deliver intact particles to lysosomes where cholesterol esters are hydrolyzed by lysosomal aicd lipase; associated apolipoproteins are degraded to small peptide and amino acid
A
Purpose of intraceullular-cholesterol transport pathway of lipid metabolism
6
Q
List 5 analytes used to predict risk for development of CAD
A
- Apo B-100 (on LDL)
- Apo E
- Homocysteine
- High sensitivity CRP (hsCRP)
- Lipoprotein
7
Q
Electrophoretic pattern of Type IIb
A
LARGE beta band
8
Q
Three intracellular uses of cholesterol esterase
A
Membrane biogenesis, stored in intracellular lipid drops after re-esterification by ACAT catalysis
9
Q
Major carrier of endogenous (hepatic origin) lipids
A
VLDL
10
Q
Secretion of triglycerides from intestine
A
B-48
11
Q
The importance of LPL and apo C-II in the formation of the VLDL remnant in the endogenous pathway
A
C-II activates LPL on the surface of endothelial cells, leading to TGL hydrolysis and free fatty acids release to peripheral cells
12
Q
Elevated VLDL and chylomicrons, cholesterol increased, moderately increased TGL, LDL and HDL normal to low
A
Mixed Hyperlipoproteinemia/Type V
13
Q
Elevated TGL w/o significantly increased cholesterol would cause increases in which two lipoproteins?
A
VLDL and chylomicrons
14
Q
The formation of LDL in the endogenous pathway
A
IDL transfers apo E, C, free cholesterol, and phospholipids to HDL in the circulation making LDL
15
Q
Three signs and symptoms of the metabolic syndrome
A
- Central obesity
- Hypertension
- High blood glucose
- High TGL
- Low HDL
16
Q
Explain the process of dietary triglyceride metabolism
A
- Digested in the duodenum and absorbed in proximal ileum
- Pancreatic and intestinal lipase and bile acids hydrolyze triglycerides to glycerol, monoglycerides, and fatty acids
17
Q
Specific concentrations of TGL
- Desirable
A
< 150 mg/dL
18
Q
Electrophoretic pattern of Type IIa
A
Increased beta band on electrophoresis
19
Q
The effect of excess intracellular cholesterol on the cell
A
Downgrades HMG-CoA reductase activity, inhibits expression of LDL receptor, induces the synthesis of proteins involved in reverse cholesterol transport
20
Q
HDL cholesterol precipitation methods
A
- Precipitate apo B-containing lipoproteins
- Centrifuge and analyze supernatant (HDL)
- Use direct assay to mask non-HDL fractions so they don’t react w/ enzymes used to measure cholesterol
21
Q
The importance of apolipoprotein C-II and LPL for TGL hydrolysis in exogenous pathway
A
C-II activates LPL causing rapid hydrolysis of TGL into free fatty acids to be taken up by adipose or muscle cells
22
Q
Lack proper forms of apo E to allow liver to identify chylomicron remnants and IDL, diagnosed at age 20 or higher, increased total cholesterol and TGL, normal to decreased LDL, increased IDL
A
Dysbetalipoproteinemia/ Type III
23
Q
Electrophoretic pattern of Type I
A
Intense band at point of application or at chylomicrons
24
Q
The specific site in the intestine where chylomicrons are assembled in the exogenous pathway
A
Intestinal epithelial cells
25
Four detrimental effects of oxidized LDL
1. Macrophages are transformed into foam cells
2. Cytotoxic effects are exerted on endothelial cells
3. Platelet activation is increased
4. Migration and proliferation of smooth muscle cells stimulated
26
How the chylomicron remnant is formed in the exogenous pathway
What remains of free fatty acids to enter the liver (Cholesterol esters) (B-48 and Apo E)
27
VLDL
- % TGL
- % Phospholipids
- % Cholesterol
- % Protein
- Apolipoproteins
- 55% TGL
- 18% phospholipid
- 19% cholesterol
- 8 % protein
- apo B-100, C-I, C-II, C-III, E
28
Genetic disorder in which there is a defect in synthesis or secretion of lipoproteins containing apo B; LDL is absent in homozygotes; total cholesterol usually < 30 mg/dL
Abetalipoproteinemia
29
Specific concentrations of LDL
| - High
160-189 mg/dL
30
Fat absorption problems causing failure to thrive in infancy, mental and physical retardation, blindness, and acanthocytes on PBS
Abetalipoproteinemia
31
(At least) five modifiable risk factors for coronary artery disease
1. Hypertension
2. Smoking
3. Obesity
4. Diet
5. Alcohol
6. Stress
7. High lipids
32
Basic structure of cholesterol
A steroid alcohol w/ 27 carbon atoms arranged in a tetracyclical sterane ring system
33
Total cholesterol 40-125 mg/dL, normal to elevated TGL, familial severe HDL and apo A-I deficiency, hyperplastic orange-yellow tonsils and adenoids plus hepatosplenomegaly
Hypoalphalipoproteinemia (Tangier disease)
34
Specific concentrations of TGL
| - Very high risk
>=500 mg/dL
35
Transports dietary lipids that are absorbed by the intestine to the liver and peripheral tissues; TGL digested in duodenum and proximal ileum through action of pancreatic and intestinal lipases and in the presence of bile acids
Purpose of the exogenous pathway for dietary lipids
36
Empirical formula and three sources of fatty acids
R-COOH
1. Diet (largest source)
2. Adipose tissue
3. Biosynthesis of all but the "essential fatty acids"
37
Discuss progression from fatty streaks to fibrous plaques to complicated lesions in atherosclerosis
Plaque deposited in blood vessels, inflammation allows lipids to come in and start consuming fat (foam cells), lumen decreases, accumulation of fibrous cap, then platelet thrombosis and fibrin deposits creating a necrotic core w/ debris
38
Three uses of intracellular cholesterol hepatocytes
Repackaged and secreted on lipoproteins converted to bile salts; directly secreted into bile
39
Specific appearance of serm/plasma w/ expected CHOL or TGL concentrations
- Normal TGL
Clear
40
Electrophoretic mobilities of LDL
Beta region
41
Specific appearance of serm/plasma w/ expected CHOL or TGL concentrations
- TGL > 500 mg/dL
Opaque/milky
42
Core of nonpolar, neutral lipids surrounded by more polar amphipathic lipids on the surface, contains one or more specific proteins; DIAGRAM IN LECTURE
Structure of lipoproteins
43
Common disorder, elevated VLDL, elevated LDL, increased total cholesterol, increased TGL
Combined hyperlipoproteinemia/Type IIb
44
Facilitates uptake of chylomicron remnant and IDL
Apo E
45
Specific concentrations of TGL
| - Borderline
150-199 mg/dL
46
Macrophages accumulate excess cholesterol and become these (atherogenic)
Foam cells
47
The importance of apo E for hepatic uptake of the chylomicron remnant in the exogenous pathway
Required for hepatic endocytosis (entrance into the liver)
48
Describe the catabolic process of beta-oxidation
Shortens fatty acid chain from carboxyl end of molecule to form acetyl-CoA; condensed w/ oxaloacetate to form citrate to enter the Kreb's cycle (yields more energy than catabolism at glucose)
49
Reagents used in enzymatic cholesterol methods
Cholesterol esterase and oxidase
50
Specific concentrations of LDL
| - Near/above optimal
100-129 mg/dL
51
Six harmful effects of trans fatty acids
1. Not recognized by enzymes
2. If incorporated into cell membrane, membrane is more dense and function is altered
3. Raises LDL and triglycerides
4. Lowers HDL
5. Increases risk of cardiovascular disease
6. Has a detrimental effect on brain/nervous system
52
Plasma appearance in Type IIb
Slightly turbid
53
Activates LCAT
A-IV, C-1
54
Describe the basic structure and the major function of triglycerides
3 fatty acids attached to glycerol;
| major function: storage of fat in the tissues
55
Enzyme deficiency and typical symptoms of Tay-Sachs disease
Deficiency: hexosaminidase
Symptoms: psychomoter deterioration, dementia
56
Six functions of phosphoglycerides
1. Components of cell membranes
2. Enzyme activators
3. Metabolic fuels
4. Signaling molecules
5. Surfactant
6. Component of lipoproteins
57
Reagents used in Liebermann-Burchard method
Sulfuric acid, acetic anhydride
58
Specific concentrations of low value of HDL cholesterol
< 40 mg/dL
59
Friedewald formular to calculate LDL concentration
LDL = TC-- (VLDL + HDL); VLDL = TGL/5
60
Autosomal recessive, usually detected before 10 years of age, TGL levels usually >1000, elevated chylomicrons only
Hyperchylomicronemia/Type I
61
Chylomicrons
- % TGL
- % Phospholipids
- % Cholesterol
- Apolipoproteins
- 86% TGL
- 7% phospholipids
- 5% cholesterol
- apo A-I, A-IV, B-100, B-48, C-I, C-II, C-III, E
62
Importance of emulsification of cholesterol
Necessary to solubilize cholesterol before absorption, this occurs by the formation of mixed micelles
63
Reagents used in Abell method
Cholesterol esters chemically hydrolyzed then perform Liebermann-Burchard
64
Five patient preparation instructions for proper lipid study specimen collections
1. 12-14 hour fast (water only)
2. Habitual diet and activity
3. Stable weight over past 4 weeks
4. No acute/recent illness, injury, or surgery (MI or CABG)
5. No lipid-raising or lipid-lowering drugs
6. Repeat in 1-4 weeks to diagnose
65
(At least) five non-modifiable risk factors for coronary artery disease
1. Gender
2. Age
3. Family history
4. Race
5. Diabetes mellitus
66
Four functions of lipoproteins
1. Facilitate direct cellular uptake and catabolism of lipoproteins
2. Serve as structural component
3. Serve as cofactor to regulate enzymes
4. Facilitate transfer of lipids b/w lipoproteins
67
5 general functions of lipids
1. Serve as hormones or hormone precursors
2. Aid in digestion
3. Provide energy storage and metabolic fuels
4. Provide functional and structural components in biomembranes
5. Form insulation to prevent heat loss or to allow nerve conduction
68
Pumps cholesterol out of the cells in the reverse-cholesterol transfer pathway
ABCA-1 transporter
69
Electrophoretic mobilities of chylomicrons
At point of application
70
Markedly elevated VLDL, normal LDL, increased TGL, normal cholesterol; deficiency of LPL or apo C-II
Hyperprebetalipoproteinemia/Type IV
71
Genetic disorder, LDL concentrations about 1/10 of normal, total plasma cholesterol may be < 30 mg/dL, normal TGL
Hypobetalipoproteinemia
72
Purpose is to remove excess cholesterol from peripheral cells and return it to the liver for excretion; mediated by HDL
Reverse cholesterol transport pathway of lipid metabolism and the lipoprotein that mediates it
73
Electrophoretic pattern of Type III
Broad beta band of abnormal composition
74
Electrophoretic mobilities of HDL
Alpha1 region (moves fastest to anode)
75
Cofactor of LCAT
A-I
76
Function and different sites of action for lecithin-cholesterol acyltransferase (LCAT) and acylocholesterol acyltransferase (ACAT)
Both reduce cytoxicity of free cholesterol
LCAT: extracellularly
ACAT: intracellularly
77
Thickening, hardening, and loss of elasticity in artery walls
Arteriosclerosis
78
The importance of apo B-100 in the intracellular-cholesterol transport pathway
LDL is recognized by LDL receptor
79
Purpose is to transfer hepatic-derived lipids, especially TGLS, to peripheral cells for energy metabolism
Endogenous pathway for lipids
80
Specific concentrations of total CHOL
| - Desirable
< 200 mg/dL
81
Specific concentrations of TGL
| - High risk
200-499 mg/dL
82
Specific concentrations of LDL
| - Optimal
<100 mg/dL
83
Secretion of triglycerides from liver binding protein to LDL receptor
B-100
84
Intracellular enzyme responsible for cholesterol ester hydrolysis in the intracellular-cholesterol transport pathway
Lysosomal acid lipase
85
HDL
- % TGL
- % Phospholipids
- % Cholesterol
- % Protein
- Apolipoproteins
~50% protein ("high density")
~50% lipids (~4% TGL, ~30% phospholipids, ~16% cholesterol esters)
- apo A-I and A-II
86
Two functions of cholesterol
Helps organize cell membranes and controls permeability
87
Plasma appearance of Type IV
Slightly cloudy, cloudy, or opaque
88
Specific concentrations of total CHOL
| - High
>=240 mg/dL
89
The importance of the presence of only apo B-100 on LDL in the endogenous pathway
B-100 is the receptor protein that allows LDL to bind to hepatic or extrahepatic cells to deliver its cholesterol load
90
Specific concentrations of LDL
| - Very high
>=190 mg/dL (VERY BAD)
91
The importance of mixed micelle formation in the absorption of dietary cholesterol in the exogenous pathway
Bile acids act as detergents; helps to transport cholesterol easily to epithelial cells to be absorbed
92
Plasma appearance of Type IIa
Clear/orange
93
Disposition of fatty acids after TGL hydrolysis in exogenous pathway
Free fatty acids combine w/ ALB and are taken up by muscle cells as an energy source or by adipose cells for energy storage as TGL
94
Specific concentrations of total CHOL
| - Borderline high
200-239 mg/dL
95
TGL concentration above which the Friedewald formula is invalid
TGL > 400 mg/dL5
96
Electrophoretic mobilities of VLDL
Pre-beta region
97
The formation of IDL in the endogenous pathway
Progressive lipolysis of TGL from the core of VLDL transforms it to IDL
98
Specific appearance of serm/plasma w/ expected CHOL or TGL concentrations
- Increased CHOL/TGL
Orange/yellow tint
99
Specific concentrations of LDL
| - Borderline high
130-159 mg/dL
100
Importance of esterification of cholesterol
In order to reduce the cytotoxicity of free cholesterol
101
A form of arteriosclerosis caused by focal accumulation of lipids, complex CHOs, blood, fibrous tissue, and calcium
Atheroscloerosis
102
Specific appearance of serm/plasma w/ expected CHOL or TGL concentrations
- TGL 200-499 mg/dL
Hazy/turbid
103
Specific concentrations of high HDL cholesterol
>=60 mg/dL (GOOD)
104
Elevated LDL, normal TGL, increased cholesterol (800-1200 mg/dL), 3 variant forms
Hyperbetalipoproteinemia/Type IIa
105
Electrophoretic pattern of Type IV
Increased pre-beta band
106
Four reasons why HDL is considered "good" cholesterol
1. Anti-clotting properties
2. Promotion of the efflux of excess cellular cholesterol
3. Antioxidant properties
4. Anti-inflammatory properties
107
Elevated cholesterol w/o increased TGL may be due to increases in which three lipoprotein fractions?
LDL, IDL, and VLDL
108
Enzyme deficiency and typical symptoms of Niemann-Pick syndrome
Deficiency: sphingolyelinase
Symptoms: hearing problems, psychiatric problems, epilepsy, dysphagia, ataxia, learning difficulties, clumsiness
109
Cofactor of LPL
C-II
110
IDL
- % TGL
- % Cholesterol
- % Protein
- % Phospholipids
- Apolipoproteins
- 23% TGL
- 37% cholesterol
- Intermediate concentrations of lipid and protein b/w VLDL and LDL
- apo B-100 and E
111
Three important pancreatic enzymes and their substrates in the exogenous pathway for dietary lipids
Lipase, cholesterol esterase, and phospholipase A
112
Three fat-soluble vitamins (terpenes)
Vitamins A, E, K
113
Form the major lipids of cell membranes, increase rigidity, act as signal transducers in CNS, made by all cells except erythrocytes
Sphingolipids
114
The importance of cholesterol ester transfer protein (CETP) in TGL cholesterol exchange
Removes TGL from LDL and exchanges it for cholesterol esters from HDL; LDL is rich in cholesterol esters and contain ONLY B-100
115
Enzyme deficiency and typical symptoms of Gaucher's disease
Deficiency: beta-glucocerebrosidase
Symptoms: Hepatomegaly, bone pain and crisis, collapsed vertebrae, splenomegaly, thrombocytopenia, anemia, osteonecrosis, osteopenia, Erlenmeyer flask deformity
116
Plasma appearance of Type I
Creamy layer over clear plasma
117
Hydrophilic adaptation in order to transport hydrophobic lipids to tissues and organs
Function of lipoproteins
118
The major carrier of exogenous (dietary) lipids
Chylomicrons
119
Inhibits C-II activation of LPL
C-III
120
Why is it important that nascent HDL be converted to its spherical form (HDL2)?
So it can return to circulation to pick up more cholesterol
121
LDL
- % TGL
- % Phospholipids
- % Cholesterol
- % Protein
- Apolipoproteins
- 6% TGL
- 20% phospholipid
- 50% cholesterol
- 20% protein
- ONLY apo B-100
122
Plasma apperance of Type V
Opaque w/ floating creamy layer; "cottage cheese over milk"
