lipids and lipoprotein Flashcards
lipids, These are commonly referred to as __,
fats
the composition of lipids
carbon-hydrogen bonds
if the carbohydrates are bonded by glycosidic bonds, how are lipid being bonded?
tru ester bond
These are insoluble in blood and water, but soluble in ____
organic solvents (chloroform and ether).
These are primary sources of fuel;
lipids
they provide ___ to
cell membrane and allow for ____ transport.
stability; transmembrane
They require special transport mechanisms (___)
for circulation in the blood.
lipoproteins
Major lipids:
o Phospholipids,
o Cholesterol,
o Triglycerides,
o Fatty acid and
o Fat-soluble vitamins (ADEK)
are the ubiquitous constituent of all living cells
lipids
most abndant lipid
phospholipid
most atherogenic phospolipids
cholesterol
2nd most atherogenic lipid
triglyceride
according to bishop, lipid is the efficient wAy to store ___
excess calorieS
relationship of triglyceride and calories,
directly proportional, as trigly are the ones that can be stored as ADIPOSE
it is as well an integral part of the cell membrane
lipids - as all the cells has bilayer membrane made of phospholipids
the head is the ____ means __
polar - water loving
the tail is the ____ means __
non polar - water-hating
lipids are also precursors for the _
Steroid hormones, prostaglandins,
leukotrienes, and lipoxins
the lipids transported by lipoproteins, namely, ___, are also the principal lipids found in cell
membranes and intracellular lipid droplets
triglycerides, phospholipids,
cholesterol, and cholesteryl esters
build up of plaque
atherosclerosis
blood vessels are inflamed
arteriosclerosis
diseases associated with lipids
dyslipidemia
It is the most abundant lipids derived from phosphatidic acid.
Phospholipid (Conjugated Lipid)
Phospholipid (Conjugated Lipid)
It originates in the __ and ___
liver and intestine.
phospholipids It is the most abundant lipids derived from ___.
phosphatidic acid
composition of phospholipids
1 polar head and 2 tails
1 phosphorylated glycerol and 2 molecules of fatty acids
Reported to be an independent risk factor for
atherosclerosis.
phospholipids
In the lungs, it is produced by ___ in the
form of lamellar bodies.
type II pneumocytes
phospholipids
Reference value: ___ mg/dL (serum
150-380
is phospholipids a significant lipid to detect heart disease?
no.
phospholipids are as well also called as
amphiphatics- polar head and non polar tail
ref range of phospholipids
150-380 mg/dl
function of phospholipid
Alter fluid surface tension (___) - it decreases
surface tension within the alveolar space, thus allowing effective gas exchange, and prevents alveolar collapse during expiration.
surfactant
function of phospholipids
It participates in __ and ___
cellular metabolism; blood
coagulation.
in blood coagulation, phospholipids are known as a tissue factor ___
factor III
function of phospholipids
They are also important substrates for a number of
___ (e.g ., LCAT, LPL, HL);
therefore changes in the composition could adversely
affect the function of these enzymes.
lipoprotein metabolizing enzymes
function of phospholipids
Deficiency of surfactant leads to _–
neonatal respiratory distress syndrome (RDS).
Forms of Phospholipids
- Lecithin/Phosphatidylcholine: 70%
- Sphingomyelin: 20%
- Cephalin: 10%
forms of phospholipid
what is the percentage of
Lecithin/Phosphatidyl choline:
70%
forms of phospholipids
sphingomyelin %
20%
forms of phospholipids
cephalin %
10%
It is the only phospholipid in membranes that is not derived from glycerol but from an amino
alcohol called sphingosine
Sphingomyelin
It is an essential component of cell membranes (RBC and
nerve sheath).
Sphingomyelin
sphingomyelin
It accumulates in the liver and spleen of patients suffering
from ___
Niemann-Pick disease (lipid storage disorder)
Niemann-Pick disease (lipid storage disorder)
reason behind
lack of enxyme - spingomyelinase
is it used t diagnose fetal lung maturity
phospholipids
hwo do we get the fetal lung maturity for phospholipids
correlates strongly with L/S ratio > 2.
method to L/S ratio > 2
- thin layer chromatogrpahy - method of choice
- testing the microviscocity - fluorescence polarization immunoassay method
how to we determine the amount of phospholippids?
estimation of phosphorous
1 mole of Phosphorous is equivalent to how __ of phosphlipids
4%
factor of phosphorous for phospholipids
25
It is an unsaturated steroid alcohol containing four rings, and it has a single C-H side chain tail similar to fatty acid.
cholesterol
Cholesterol It is found on the
surface of lipid layers;
Cholesterol synthesized in the
__.
liver
the lipids that is not catabolized by most cells, and does not serve as a source of fuel/energy
cholesterol
cholesterol are synthesized in liver for how many percent ,,, and for diet
85%; 15%t
the only lipid that do not require fasting
cholesterol
do cholesterol participates in energy production?
nope
cholesterol’s transport and excretion is promoted by what hormonr
estrogen
chole must be measured starting at age ___ once every 5 yrs
20 y/o
desirable level of chole
<200 mg/dl
borderline cholesterol level
200- 239 mg/dl
high cholesterol level
> = 240 mg/dl
cholesterol Precursor of five major classes of steroids:
progestins, glucocorticoids, mineralocorticoids,
androgens and estrogens.
It is an Important constituent in the assembly of cell membranes and bile acids
cholesterol
used for 2nd marker for thyroid
cholesterol
hyper - high metabolism - low cholesterol
a small amount of cholesterol, after first being converted to 7-dehydrocholesterol, can also be transformed to ___ in the skin by irradiation from sunlight
vitamin D3
2 forms of cholesterol
main - cholesterol ester - 70%
Free Cholesterol (FC) - 30%
cholesterol ester are found in
plasma and serum
cholesthrol ester is bound to
fatty acids
this form of cholesterol undergoes the esterification by LCAT
cholesterol ester
inactive form of cholesterol with “protective” property and stored in cells
cholesterol ester
a form of cholesterol that is not charged, and is classified as neutral lipid and are not found on the surface of lipid layers but instead are located in the center of lipid drops and lipoproteins along with triglycerides
cholesterol ester
excess cholesterol is re-esterified by the __ and is stored until it is needed
microsomal enzyme acyl-Coa:cholesterol acyltransferase (ACAT )
It catalyzes the esterification of
cholesterol (HDL) by promoting
the transfer of fatty acids from
lecithin to cholesterol which
results in the formation of
lysolecithin and cholesterol
ester.
Lecithin-Cholesterol Acyl Transferase (LCAT)
It enables HDL to accumulate
cholesterol as cholesterol
ester.
lecithin-cholesterol acul transferase (LCAT)
free cholesterol + fatty acids
cholesterol ester
free cholesterol and phospholipids (with hydrophilic property) are found on the surface of
lipoproteins
the process of esterification is a “____” step to reduce the accumulation of free cholesterol through the action of the acyltransferase enzymes
detoxification
shape of mature hdl
sphere
Activator of LCAT: __
Apo A-1
free cholesterol is found in
It is found in plasma, serum and RBCs.
a polar non-esterified alcohol
unesterified/free cholesterol - 30%
why menopausal women increases cholesterol
estrogen came from cholesterol, it decreases chole by using it to form estrogen
since menopausal women stop producing estrogen, more chole accumulated
effect of liver disease in chole
decreases since chole came from liver
effect of kidney disease in chole
forms cholesterol crystals resulting to nephrotic syndrome
chole are stored at what temp
70C for long time
2C for short time 1-2 months
It is produced via lysosomal hydrolysis and
becomes available for membrane, hormone, and bile acid synthesis
free cholesterol
Triglycerides is also known as
TRIACYLGLYCEROL
TRIACYLGLYCEROL is made up of
1 glycerol - 3 fatty acids
It is the main storage lipid in man (adipose tissue)
Triglycerides
triglycerides has no charge which means they are water____
phobic - hydrophobic and water insoluble
Constitutes 95% of stored fat and the predominant form of glyceryl ester found in plasma.
Triglycerides
It allows the body to compactly store long carbon chains (fatty acids) for energy that can be used during fasting states between meals
Triglycerides
function of triglycerides
when TAG are metabolized, their fatty acids are released into the cells and converted into energy ‘
provides excellent insulation
product of hydrolysis of triglyceride
1 glycerol
3 fatty acids
The breakdown of TAG is facilitated by __.
lipoprotein lipase
(LPL), epinephrine and cortisol
an average person ingests, absorbs, resynthesizes, and transport ___ grams of fat daily in the body, mostly in the form of TAG
60-130g
percentage of triglyceride in terms of origin
95% dietary
fasting hrs for triglyceride
10-12 hrs
reference range for normal TAG
< 150 TAG
borderline TAG
150-199 mg/dl
high TAG range
200-499 mg/dl
very high TAG
> 500 mg/dl
characteristic of a serum for a patient with very high triglyceride
lipemic
fasting TAG >= 200 mg/dl are at risk for
coronary artery disease
because of atherogenic VLDL remnants
2 lipids that are most important in management of CAD
TAG and cholesterol
postural changes decrease TAG levels by almost __ from upright to supine position, hence, a stable position is required to ensure reliability of results
50%
A linear chain of C– H bonds that terminate with carboxyl group (–COOH).
fatty acids
fatty acids are mostly found as constituents of what lipids
phospholipids and TAG
phospholipids - 2 fatty chain
TAG - 3 fatty chain
fatty acids are mainly derived from hydrolysis of__
TAG in adipose tissues
Example: of fatty acids
palmitic acid, stearic acid, oleic acid, linoleic
acid and arachidonic acid
Classification of fatty acids As to chain
- Short-chain (4-6 carbon atoms),
- medium-chain (8-12 carbon atoms) or
- long chain (>12 carbon atoms
Classification of fatty acids As to the number of C=C bonds
- Saturated ( without double bonds) fatty acids
- unsaturated (with double bonds) fatty acids
fatty acid
1 doublke bond
mono unsaturated
saturated fatty acids remain ___ in room and high temp
solid - means high melting point
unsarturated fatty acids melting point
low melting point
saturated will increase what cholesterol?
bad cholesterol
unsaturated fatty acids will increase __
good cholesterol
what fatty acids are not associated with elevated serum LDL cholesterol
polyunsaturated and cis-monosaturated fatty acids
They provide the substance for conversion to glucose
(gluconeogenesis).
fatty acids
Main purpose: To transport TAG and cholesterol to sites of
energy storage and utilization
lipoprotein
the most hydrophibic lipidsa, such as cholesterol esters and triglycerides, are located in the ___ of the lipoprotein
core
lipids with some hydrophilicity, such as __ and __ are arranged on the surface with polar groups pointing outward
free cholesterols and phospholipids
are the major sites of beta lipoprotein
hepatocytes and enterocytes
lipoprotein lipase will liberates fatty acids from
TAG
It helps to keep the lipids in solution (solubility) during circulation through the blood stream.
Apolipoprotein
it facilitates uptake of LPP into cells through their recognition by specific cell surface receptors
apolipoprotein
what are the major apolipoprotein
ApoA-1
ApoB- 48
ApoB-100
It is the largest and the least dense of the lipoprotein
particles.
Chylomicron (CM)
It is produced in the intestine from dietary fat;
Chylomicron (CM) - intestine yan kasi exogenous
vitamin E depends on __ for absoprtion and __ for delivery to tissues
chylomicron for absorption
VLDL and LDL for delivery
It is produced in the intestine from dietary fat;
completely cleared within 6 to 9 hours post prandial.
Chylomicron (CM)
Major composition of chylomicron
: 90% TAG ( non-fasting plasma) +
1-2% protein
Apolipoproteins Chylomicron (CM)
Apolipoproteins: Apo B-48, Apo A-1, Apo C and Apo E
major apolipoprotein of chylomicron
ApoB-48
the inability to remove chylomicron after eating is the lack of what apolipoprotein
apo c2
chylomicron are removed by
hepatic lipase which is activated by apo c2
It transports EXOGENOUS/dietary TAG to liver, muscles
and fat depot.
Chylomicron
Very Low Density Lipoprotein/Pre-Beta Lipoprotein (VLDL)
It is secreted in the
liver
It transports endogenous TAG from the liver to
muscle, fat depots and peripheral tissues.
Very Low Density Lipoprotein/Pre-Beta Lipoprotein (VLDL)
Major composition:of vldl
65% TAG ( fasting plasma) + 6-
10% protein + 16% CE
major apolipoprotein of VLDL/ pre beta lipoprotein
ApoB-100
minor apolipoprotein of VLDL/ pre beta lipoprotein
ApoC and ApoE
why do hdl is called as alpha lipoprotein?
becoz in eletrophoresis, it migrates to alpha region
the endogenous pathway, production of TAG from FA by the lover takes place, with synthesis of VLDL particles containing what apolipoprotein
ApoB-100 and Apo E
It is the smallest lipoproteins but the most dense (5-
12nm).
High Density Lipoprotein/Alpha Lipoprotein (HDL)
High Density Lipoprotein/Alpha Lipoprotein (HDL)
It is produced in the
liver and intestine
It transports excess cholesterol from the tissues and
return it to the liver (reverse cholesterol transport) -
High Density Lipoprotein/Alpha Lipoprotein (HDL)
Major composition of hdl
High Density Lipoprotein/Alpha Lipoprotein (HDL)
Major composition of hdl
30% phospholipid + 45-50%
protein + 20% CE
major apolipoproteins of hdl
apo A-1
minor apolipoproteins of hdl
ApoA-II and ApoC
ncep
national cholsterol edcation program
(cutoff level) for hdl
40 mg/dL
Interpretation of hdl
< 35 mg/dl - high risk for CHD ,
< 40 mg/dl - low
>60 mg/dl - high HDL (protective)
It is the most cholesterol-rich of the lipoproteins and most
atherogenic
ldl
2nd most
atherogenic lipoprotein
vldl
It constitutes about 50% of the total LPP in plasma - the
major source of cholesterol for tissues.
Low Density Lipoprotein/Beta Lipoprotein (LDL)
It transports cholesterol to the peripheral tissues - it carries
most of the circulating cholesterol and transports
cholesterol to hepatic and extrahepatic tissues, where it is
taken up by LDL-receptor-mediated endocytosis.
Low Density Lipoprotein/Beta Lipoprotein (LDL)
It is the primary target of cholesterol lowering therapy;
primary marker for CHD risk.
Low Density Lipoprotein/Beta Lipoprotein (LDL)
It is important in assessing patients with or without
coronary heart disease (CHD).
ldl
Major composition of ldl
50% CE + 18% protein and
phospholipid
how LDL become so atherogenic
they can pass through the intima layer of vascular beds and be taken up by macrophages to make foam cells
the primary target of cholesterol-lowering therapy
LDL
the LPP that is the primary marker for coronary heart disease risk
LDL
lipoprotein that is important in assessing patients with or without CHD
LDL
major composition of LDL
50% cholesterol ester
18% protein and phospholipid
major apolipoprotein of LDL
ApoB-100
minor apolipoprotein of LDL
ApoE
ref value of LDL
<100 mg/dl
a by product of VLDL catabolism “vldl remnant “
intermediate density lipoprotein - IDL
it migrates either in the pre B or B region
IDL
defective clearance of IDL in type 3 hyperlipoproteinemia is probably due to deficiency of
ApoE-III
major lipids of IDL
endogenous TAG and cholesterol ester
kasi nga diba between siya ng beta and pre beta
so VLDL and CHOLE
si VLDL ang bahala sa endogenous TAG and si chole naman sa chole ester
major apolipoprotein of IDL
both VLDL at LDL yan so ang major apolipoprotein niyan is
ApoB-100
similar to LDL in terms of density and composition
an LDL like particle with a molecule of Apo (a) linked to Apo B 100 by a disulfide bond
lipoprotein a
where do lipoprotein a migrates in electrophoresis
migrates in the pre-b region, or sometimes between LDL and albumin
known as the “sinking pre-b lipoprotein” due to electrophoretic mobility same as VLDL but density like LDL
lipoprotein a
it is isolated in the LDL-HDL density range by ultracentrifugation
lipoprotein a
its complex structure is similar to plasminogen
lipoprotein a
is an abnormal lipoprotein found in obstructive jaundice and LCAT deficiency
lipoprotein X
a specific and sensitive indicator of cholestasis
lipoprotein X
the lipid content of lipoprotein X is mostly
phospholipid and free cholesterol (90%)
has the density of VLDL by ultracentrifugation but migrates to LDL in the B region during electrohoresis
floating B lipoprotein
b-VLDL
found in type 3 hyper lipoproteinemia or dysbetalipoproteinemia
b-VLDL
known as the VLDL-rich in cholesterol due to defective catabolism of VLDL
b-vldl
why is there an accumulation of IDL in B-VLDL
because of failure to fully convert VLDL to LDL
commonly considered as a dysfunctional HDL because native HDL is protective to atherosclerosis
oxidized HDL
preferred anticoagulant
edta plasma
fasting hrs for lipid determination
10-12 hrs
fasting state, most TAG is present in
vldl
non fasting state, most TAG is present in
chylomicron
if testing is non in non fasting samples, only _ and __ can be measured
those that aren’t affeected by diet
total cholesterol and HDL-C
the reference method for lipoprotein
ultracentrifugation
reagent for ultracentrifugation
potassium bromide with 1.063 density
can we use frozen samples for ultracentrifugation?
nope, can’t withstand freezing
expressed in svedverg units
ultracentrifugation
most anodal to least anodal pattern of lipoproteins in electrophoresis
HDL, VLDL, LDL, chlylomicrons
which lipoprotein remains only at the origin in electrophoresis
chylomicrons
in chemical precipitation what are the polyanions used
heparin sulfate
dextran sulfate
phosphotungstate
in chemical precipitation what are the divalent used
magnesium
calcium
manganese
the most consistent analytical error involved in HDL-C assay is due to the presence of a small amount of
ApoB-containing LPPs
HDL uses what polyanions and divalent cations
polyanions - dextran sulfate
divalent cations - magnesium
sample preferred for beta quantification
edta plasmsa
beta quantification combines what method
ultracentrifugation and chemical precipitation
it is an autosomal dominant disorder caused by defective or deficient LDL receptors
familial hypercholesterolemia - type 2a
an autosomal dominant disorder caused by defective or deficient LDL receptors - LDLR gene on chromosome 19
familial hypercholesterolemia
mataas ang cholesterol, type 2a to kasi about LDL si type 2a
clinical findings for familial hypercholesterolemia
xanthelasma and planar (tendon) xanthomas
involves accumulation of plasma VLDL rich in cholesterol and chylomicron
familial dysbetalipoproteinemia
type 3 hyperlipoproteinemia
this involves both the endogenous and exogenous pathway of lipoprotein metabolism
familial dysbetalipoproteinemia - type 3 hyper lipoproteinemia
lab findings of a sample with familial dysbetalipoproteinemia
equal elevations of cholesterol and TAG and the presence of b-vldl
pathognomonic feature fore dysbetalipoproteinemia
broad abnormal band between VLDL and LDL (b-vldl)
an autossomal recessive disorder with defective ApoB synthesis
abetalipoproteinemia
abetalipoproteinemia is also called as
bassen-kornzweig syndrome
VLDL, LDL, and chylomicrons are all not found in plasma due to absence of ApoB containing lipoprotein
abetalipoproteinemia
describe the concentration of chole and TAG in abetalipoproteinemia
decrease, since walang carrier
also associated with defects in the microsomal triglyceride transfer protein
abetalipoproteinemia
also associated with the defects in the absorption of fat soluble vitamins AEK; deficient fat soluble vitamins
abetalipoproteinemia - bassen kornzweig syndrome
the only fat soluble vitamin that does not need chylomicron for absorption, thus, not affected by abetalipoproteinemia pr bassen kornzweig syndrome
vitamin D
although si A and K is di rin nagre-rely kay CM, they are still affected somehow
characterized by cerebellar ataxia, acanthocytosism and fat malabsorption
abetalipoproteinemia
due to ApoB deficiency resulting from point mutation in ApoB
hypobetalipoproteinemia
is an inherited disorder of lipid metabolism in which there are accumulations of spingomyelin in the bone marrow, spleen, and lymph nodes
niemann-pick disease (lipid storage disease)
involves deficiency of enzymes responsible for removing phosphorylcholine from sphingomyelin by sphingomyelinase
niemann-pick disease
a rare autosomal recessive disorder characterized by markedly reduced or almost deficient HDL due to a mutation in the ABCA1 gene on chromosome 9
tangier disease
also associated with deficiency of ATP binding cassette protein A1
ABCA1
a protein that enables cholesterol to exit the cell, upon which it combines with ApoA1 to form HDL
ABCA1
lab findings of tangier diease
low blood chole primarily the HDL
clinical findings of tangier disease
orange or yellow discoloration of the tonsils and pharynx
a rare autosomall recessive disorder that presents in childhood with abdominal pain and pancreatitis
lipoprotein lipase deficiency
the inability to clear chylomicron particles, creating the classic type 1 chylomicronemia syndrome
lipoprotein lipase deficiency
describe the TAG in lipoprotein lipase deficiency
10,000 mg/dl
ang high value ng TAG is >500 mg/dl and normal is 149 mg/dl
deficiency of what apolipoprotein will result into chylomicronemia
ApoCII kasi siya ang nagceclear ng CM within 6-9 hrs after eating
lecithin cholesterol acyl transferase deficiency
what is the milder form of deficiency
fish eye disease
lab findings for lecithin cholesterol acyl transferase deficiency
HDL-C < 10 mg.dl
total cholesterol is normal or high
recall:
LCAT helps in esterification of chole to form lysolecithin and cholesterol ester
enables HDL to accumulate cholesterol as cholesterol ester
clinical findings for lecithin cholesterol acyl transferase deficiency
corneal opacities, normochromic anemia, and renal failure in young adults
an inherited neurodegenerative disorder of lipid metabolism characterized by a deficiency of the enzyme hexosaminidase A, which results in the accumulation of sphingolipids in the brains
tay-sachs disease
this syndrome is distinct from abetalipoproteinemia, as only ApoB-48 appears to be affected
chylomicron retention disease (anderson’s disease)
characterized by hypocholesterolemia, chronic diarrhea failure to thrive, and deficiency of vitamin E, the latter can lead to neurogenic deficits
chylomicron retention disease (anderson’s disease)
clinical findings of chylomicron retention disease (anderson’s disease)
fat malabsorption and low levels of plasma lipids
is an autosomal recessive disorder wherein plant sterols are absorbed and accumulate in plasma and peripheral tissues
sitosterolemia
a block in the progression from chylomicron to chylomicron remnants results in accumulation of CM most likely caused by LPL deficiency
type 1
a block in LDL metabolism and defective ApoB that does not bind to LDL receptor
type 2 hyperlipoproteinemia
may also be caused by a mutant LDL receptor that does not recognized ApoB
type 2
the presence of floating b-vldl in type _____ is due to failure to convert VLDL to LDL causing IDL to accumulate
type 3
a block in conversion of VLDL to IDL and LDL, but LDL is normal
VLDL - type 4
the production of excess insulin and the use of antischizoprenic drugs lead to ____
hypertriglyceridemia or type 4 hyperlipoproteinemia 1
this lipoprotein’s function is to deliver cholesterol and trigkyceride to various tissues
apo B
