C - Chapter IX: Lipids and Lipoproteins Flashcards
(154 cards)
1
Q
: organic substances which are soluble in nonpolar organic solvents (chloroform and ether) and insoluble in polar solvents (water)
A
Lipids
2
Q
nonpolar organic solvents
A
(chloroform and ether)
3
Q
polar solvents
A
(water)
4
Q
: yield fatty acids on hydrolysis OR complex alcohols the can combine with fatty acids to form esters
A
Lipids - chemically
5
Q
: cholesterol, triglycerides, phospholipids and non-esterified fatty acids
A
human plasma lipids
6
Q
: macromolecule which consists of varying proportions of protein, cholesterol, triglyceride and phospholipid
A
Lipoproteins
7
Q
water-soluble, thus, it facilitates the transport of the lipids in the circulation
A
Lipoproteins
8
Q
are diverse in terms of their structure and function
A
Lipids
9
Q
Secondary energy source
A
TRIGLYCERIDE / Neutral FAT
10
Q
Serves as a thermal insulator
A
TRIGLYCERIDE / Neutral FAT
11
Q
Protects tissues from physical trauma
A
TRIGLYCERIDE / Neutral FAT
12
Q
Precursor of biological hormones
A
CHOLESTEROL
13
Q
Source of bile acids
A
CHOLESTEROL
14
Q
Component of the Cell membrane
A
CHOLESTEROL
15
Q
Component of the Cell membrane
A
PHOSPHOLIPIDS
16
Q
Associated with vital life processes (e.g. CNS)
A
PHOSPHOLIPIDS
17
Q
also known as triacylglycerol
A
TRIGLYCERIDES
18
Q
transported by chylomicrons (exogenous) and VLDL (endogenous)
A
TRIGLYCERIDES
19
Q
Complete Hydrolysis:
A
3 FA + glycerol
20
Q
Partial Hydrolysis:
A
2 FA + monoglyceride
21
Q
Absorption: = via the portal route
A
Glycerol (H2O-soluble)
22
Q
Absorption: = via the lymphatic route
A
Fatty acids (H2O-insoluble)
Monoglyceride (H2O-insoluble)
23
Q
Synthesis of TG from
A
monoglyceride & glycerol
24
Q
: degradation of the fatty acids by 2C atoms with subsequent production of Acetyl CoA
A
β-oxidation of fatty acids in the mitochondria
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found exclusively in animals and humans
CHOLESTEROL
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contains cyclopentanoperhydrophenanthrene ring
CHOLESTEROL
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contains 27 C atoms
CHOLESTEROL
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(?) in the intestines comes from the diet, bile, intestinal secretions and cells
cholesterol
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to be absorbed, it has to solubilized by the formation of mixed micelles containing unesterified cholesterol, fatty acids, monoglycerides, phospholipids and conjugated bile acids
cholesterol
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90% of body's (?) is synthesized by the liver and gut from simpler molecules like Acetyl CoA
cholesterol
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complexing of cholesterol with a fatty acid; this process enhances the lipid carrying capacity of lipoproteins
Esterification
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is mainly esterified in the vascular compartment
Cholesterol
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Cholesterol
Catalyzed by:
− LCAT
− ACAT
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− LCAT –
Lecithin Cholesterol Acyltransferase (in plasma)
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− ACAT –
Acyl Cholesterol Acyltransferase (intracellularly)
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transported by LDL to the cells
Cholesterol
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transported by HDL out of the cells
Cholesterol
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(?) that reaches the liver is either secreted unchanged into bile (free cholesterol) or metabolized to form bile acids
cholesterol
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LIPOPROTEINS: MAJOR CLASSES
1. Chylomicron (CM)
2. Very-Low-Density Lipoprotein (VLDL)
3. Intermediate Density Lipoprotein (IDL)
4. Low-Density Lipoprotein (LDL)
5. High-Density Lipoprotein (HDL)
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Synthesized & released from the SI (Exogenous pathway)
Chylomicron (CM)
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very rich in triglycerides (80%)
Chylomicron (CM)
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transports dietary fat
Chylomicron (CM)
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relatively poor in cholesterol, phospholipids and proteins
Chylomicron (CM)
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Proteins: Apo B-48, AI, AII, AIV, C (1-2%)
Chylomicron (CM)
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when present in high levels : milky plasma (floating creamy layer)
Chylomicron (CM)
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synthesized and released from the liver
Very-Low-Density Lipoprotein (VLDL)
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transports cholesterol & triglyceride which are synthesized in the liver (endogenous pathway)
Very-Low-Density Lipoprotein (VLDL)
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smaller than chylomicrons
Very-Low-Density Lipoprotein (VLDL)
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elevated levels produce a turbid plasma
Very-Low-Density Lipoprotein (VLDL)
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contain : 50% triglycerides, 40% cholesterol and phospholipid, 10% protein
Very-Low-Density Lipoprotein (VLDL)
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Proteins: Apo B-100 & Apo C-II
Very-Low-Density Lipoprotein (VLDL)
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endogenous pathway
Very-Low-Density Lipoprotein (VLDL)
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Exogenous pathway
Chylomicron (CM)
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derived from VLDL hydrolysis by lipoprotein lipase (LPL)
Intermediate Density Lipoprotein (IDL)
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partly depleted of triglyceride
Intermediate Density Lipoprotein (IDL)
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contains an almost equal amount of triglyceride & cholesterol
Intermediate Density Lipoprotein (IDL)
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Proteins: Apo B and E
Intermediate Density Lipoprotein (IDL)
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produced from the action of LPL on IDL
Low-Density Lipoprotein (LDL)
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consists of 50% cholesterol, 25% protein, 20% phospholipid and 5% of triglycerides
Low-Density Lipoprotein (LDL)
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produced & catabolized in the liver & intestines
High-Density Lipoprotein (HDL)
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Contains Apo AI & Apo AII
High-Density Lipoprotein (HDL)
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richest in protein (50% of its weight is protein)
High-Density Lipoprotein (HDL)
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involved in reverse cholesterol transport (excess cholesterol is returned from the tissues to the liver)
High-Density Lipoprotein (HDL)
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ABNORMAL LIPOPROTEINS
Lipoprotein(a) or Lp(a)
LpX Lipoprotein
β-VLDL (“floating β” lipoprotein)
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similar to LDL in terms of density and overall composition
Lipoprotein(a) or Lp(a)
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abnormal lipoprotein found in patients with obstructive biliary disease, and in patients with familial lecithin:cholesterol acyltransferase (LCAT) deficiency
LpX Lipoprotein
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abnormal lipoprotein that accumulates in type 3 hyperlipoproteinemia
β-VLDL (“floating β” lipoprotein)
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Richer in cholesterol than VLDL
β-VLDL (“floating β” lipoprotein)
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– protein portion of lipoproteins
APOLIPOPROTEINS
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: major protein of HDL and chylomicron
Apolipoprotein A
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- originate in the intestine or liver
Apolipoprotein A
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: major protein of all lipoproteins except HDL
Apolipoprotein B
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(found in lipoprotein formed in the liver)
Large B or B100
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(found in lipoprotein formed in the S.I.)
Small B or B48
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: major protein of VLDL and chylomicrons and a minor protein of HDL and LDL
Apolipoprotein C
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: function as a transfer protein •
Apolipoprotein D
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: plays a significant role in the recognition & catabolism of chylomicron remnant and IDL via specific receptors in hepatic cells
Apolipoprotein E
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Biologic variation
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fasting – ideally fast for
12 hours3.
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Posture- [?] decrease noted in TC, LDL-C, HDL-C after [?] of recumbent position4.
10%
20 mins
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Venous vs capillary samples – capillary levels generally [?] than venous
lower
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Plasma vs serum – either can be used when only [?] and [?] are measured and [?] is calculated from these three measurements
cholesterol, triglycerides
HDL-C
LDL-C
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Storage – generally, [?] can be satisfactorily analyzed
frozen samples
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A. COLORIMETRIC DETERMINATION of CHOLESTEROL Stepwise Methods
1. Direct Colorimetric / One-Step
2. Two-Step Method
3. Three-Step Method
4. Four-Step Method
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serum is combined with the color reagent then incubated to allow color reaction to occur
Direct Colorimetric / One-Step
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Direct Colorimetric / One-Step Methods:
Watson’s, Ferro-Ham, Pearson, Zlatkis
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Liebermann-Burchard Reaction Reagents:
Acid anhydride, conc. H2SO4
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Liebermann-Burchard Reaction End-product:
cholestapolyene sulfonic acid (emerald green)
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Salkowski’s Reaction Reagents:
conc. HAc, Ferric ions
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Salkowski’s Reaction End-product:
cholestapolyene carbonium ion (reddish-purple)
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Involves 1extraction step prior to 2colorimetric reaction
Two-Step Method
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Eliminates protein interference
Two-Step Method
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Two-Step Method - Methods:
Carr-Drekter, Saifer-Kammer, Leoffler-McDougold
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Requires 1extraction w/ petroleum ether followed by 2 saponification and then 3colorimetric determination
Three-Step Method
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Standard method
Three-Step Method
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Three-Step Method - Method:
Abell-Kendall
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Requires 1extraction, 2saponification, 3purification with digitonin then 4colorimetric determination
Four-Step Method
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Considered as the reference method
Four-Step Method
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Four-Step Method - Methods:
Schoenheimer-Sperry, Sperry-Webb
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cholesteryl ester + water ----[?] ----> cholesterol + FFA
cholesterol esterase
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cholesterol + O2 ----[?]----> cholest-4-en-3-one + H2O2
cholesterol oxidase
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Colorimetric (most common)
Hantzsch-Lutidine Reaction
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Hantzsch-Lutidine Reaction
Formaldehyde + acetylacetone + NH4 [?] (yellow @ 410 nm)
3,5-diacetyl-1,4- dihydrolutidine
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Van Handel and Zilversmit
Formaldehyde + H2SO4 + chromotropic acid (CTA) [?]
pink chromophore
105
Weiland Method
glycerophosphate + NAD ---[?] ---> DHAP + NADH + H
glycerophosphate DH
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Weiland Method
NADH + tetrazolium dye ---[?]---> formazan + NAD (340nm)
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Trinder Reaction
glycerophosphate + O2 ---[?]---> DHAP + H2O2
glycerophosphate oxidase
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Trinder Reaction
H202 + reduced chromogen --→ [?]
Quinoneimine dye
109
Eggstein and Kreutz method
ADP + PEP ---[?] ---> ATP + pyruvate
pyruvate kinase
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Eggstein and Kreutz method
pyruvate + NADH + H ---LDH---> [?] (340 nm)
lactate + NAD
111
automated homogenous assays
HDL-C Determination
112
enzymatic method
HDL-C Determination
113
for calculation of LDL-c and VLDL-c
Friedewald calculation
114
cannot be used when TG is >400 mg/dL
Friedewald calculation
115
LDL-c
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VLDL-c
117
VLDL-C in mmol/L
118
DeLong, 1986:
VLDL in mmol/L =
VLDL in mg/dL
119
LDL Cholesterol (mg/dL) Optimal
<100
120
LDL Cholesterol (mg/dL) Near optimal/above optimal
100 – 129
121
LDL Cholesterol (mg/dL) Borderline high
130 – 159
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LDL Cholesterol (mg/dL) High
160 – 189
123
LDL Cholesterol (mg/dL) Very high
≥ 190
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Total cholesterol (mg/dL) Desirable
<200
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Total cholesterol (mg/dL) Borderline high
200 – 239
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Total cholesterol (mg/dL) High
≥ 240
127
HDL cholesterol Low
HDL cholesterol <40
128
HDL cholesterol High
≥ 60
129
Triglycerides Normal
<150
130
Triglycerides Borderline high
150 – 199
131
Triglycerides High
200 – 499
132
Triglycerides Very high
≥ 500
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diseases associated with abnormal lipid concentrations
Dyslipidemias
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Dyslipidemias - multifactorial :
− genetic abnormalities
− environmental/lifestyle imbalances
− secondary to other diseases
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Hyperchylomicronemia
Type I
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Creamy layer; Clear to Slightly Turbid
Type I
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Mod. Increase to markedly increased TG
Type I
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Increased LDL
Type IIa
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- Premature atherosclerosis
Type IIa
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- Familial Hypercholesterolemia
Type IIa
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Clear w/ Yellow Orange tint
Type IIa
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Increased cholesterol & normal TG
Type IIa
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Increased β and pre-β due to deficiency of LDL receptors
Type IIb
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Clear to Slightly Turbid
Type IIb
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Increased cholesterol & mod. Increased TG
Type IIb
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Broad merging of β and pre-β Increased IDL
Type III
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Thin cream layer Turbid to opaque
Type III
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Increased cholesterol & mod. to marked increase in TG
Type III
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Inc. pre-β Increased VLDL
Type IV
150
Turbid to opaque
Type IV
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Normal to slight increase in cholesterol & mod. to marked increase in TG
Type IV
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Increased chylomicron & VLDL
Type V
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Thick creamy layer Turbid to opaque
Type V
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Mod. increase in cholesterol & marked increase in TG
Type V
