Lipid Metabolism Flashcards
(167 cards)
1
Q
How are lipids transported?
A
by lipoproteins (water soluble)
2
Q
What is the origin of lipids?
A
-Exogenous (dietary sources)
-Endogenous (synthesized in the liver)
3
Q
Definition of lipids?
A
a biological substance that is insoluble in water, but soluble in
organic solvents such as alcohol, chloroform, ether and acetone.
** some of phospholipids are not soluble in acetone & some have a limited
solubility in H2O
4
Q
______ is important for reducing in lipid synthesis.
A
NADPH
5
Q
What is the primary source of fuel for the body?
A
lipids
-50% of daily calories
6
Q
What is the structural functions of lipids?
A
Components of cell membranes & other cell structures,
giving the cell membrane stability (& rigidity) and allowing
for transmembrane transport of important molecules
7
Q
What is the hormonal function of lipids?
A
steroid hormones
8
Q
Lipids functions for heat retention (brown fat) and ________ conduction (Myeline sheath)
A
nerve
9
Q
*Energy can be generated from what major lipid?
A
(Free) fatty acids
10
Q
What are the major lipids?
A
-(Free) Fatty Acids
* Phospholipids
* Cholesterol (Free & Esterified)
* Triglycerides
* Glycolipids
* Prostaglandins
11
Q
- Consist of glycerol esters combined with free fatty acids
- Constitute majority of Neutral Fat (95% of tissue storage fat)
A
Triglycerides***
12
Q
What is esterified cholesterol?
A
One fatty acid and one cholesterol (becomes hydrophobic)
13
Q
What is like a hormone but not released into circulation, works locally?
A
Prostaglandins
14
Q
What are triglycerides composed of?
A
3 fatty acids
15
Q
How much of fatty acids are free?
A
Only a small percentage
Most are part of triglycerides
16
Q
___________ supply almost half the calories burned for energy.
A
Fatty acids
17
Q
What does saturated fatty acids depend on?
A
no double bonds
· Mono-Unsaturated, one double bond,
· PolyUnsaturated, 2 or more double bonds
18
Q
Short chain FA are ______ carbon atoms.
A
4-6
19
Q
Medium-chain FA are _____ carbon atoms.
A
8-12
20
Q
Long-chain FA are ______ carbon atoms.
A
greater than 12
-needs special carriers (other than albumin)
21
Q
Which is flexile, trans or cis form of fatty acids?
A
cis
22
Q
Essential component of “Cell Membranes”
A
Phospholipids
23
Q
Act as detergents in clearing other fats out of the body
AMPHIPHILIC STRUCTURE ENABLES BOTH FUNCTIONS
A
Phospholipids
24
Q
Phospholipids serve as constituents of cell membranes and outer shells of ____________ molecules
A
lipoprotein
25
***Important phospholipids include:
✓ Lecithin (phosphatidyl choline) P choline
✓ Cephalins P ethanolamine, inositol, serine
✓ Spingomyelin (Spingolipid)
26
Spingomyelin (Spingolipid) have a _______ backbone.
Sphingosine
27
***Phospholipids are synthesized by...
the liver & intestinal epithelium
28
Lung surfactants are a mixture of _________ that decrease the fluid tension of the alveoli (preventing them from collapse)
lipoproteins
29
What causes Respiratory Distress Syndrome?
When premature infants do not secrete adequate amounts of lung surfactant thereby making lung expansion difficult
30
What phospholipids are examined to determine fetal lung maturity?
Amniotic fluid phospholipids
L/S (Lecithin: Sphingomyelin) ratios greater than 2 ----> decreased risk
31
L/S ratio alone is not a good predictor in...
diabetic, hypertensive and intrauterine growth retardation
32
***Lung maturity also correlates with the presence of....
Phosphotidyl glycerol
Surfactant containing PG (>2.1 mg/L) ---> increase surfactant stability****
33
Synthesized endogenously from acetyl-CoA
cholesterol
34
* Unsaturated steroid alcohol
* High molecular weight—
4 perhydrocyclophenanthrone rings with side chain
Cholesterol
35
What enzyme do most cholesterol drugs work on?
HMG-CoA Reductase
(rate limiting enzyme)
-if this works endogenous cholesterol synthesis goes down. Therefore decreasing cholesterol.
36
What is found almost exclusively in animals?
cholesterol
37
***Important functions of cholesterol include:
1. Manufacture and repair of cell membranes
2. Synthesis of **bile acids
3. Synthesis of Vitamin D
4. Precursor of five major classes of Steroid Hormones
38
Precursor of five major classes of Steroid Hormones?
1) Progestins
2) Glucocorticoids
3) Mineralocorticoids
4) Androgen
5) Estrogen
39
The only fat that cannot be stored in the body
cholesterol *****
-excess gets made to bile acids and goes to intestines
40
What effect does aldosterone have on Mg, H, K and Na?
excretion of Mg, H, and K
reabsorption of Na
41
How is mean arterial pressure calculated?
MAP = CO x PR
42
How does the body obtain cholesterol?
Cholesterol in blood may be absorbed through diet, or endogenously synthesized in the liver
43
How is cholesterol excreted?
via bile salts into the intestinal tract***
-cannot be stored
44
About ____% of total body cholesterol is in stationary tissue (skin and muscle)
70
45
Only about ____% of total body cholesterol is mobile in the plasma.
30
- 1/3 free; 2/3 esterified with FA
46
How does HDL cholesterol get cleared?
HDL protien --> enzymes (LCAT and ACAT) ---> ester ---> free cholesterol ---> to be cleared via liver --> bile salts --> intestinal tract
47
What does LCAT stand for?
Lecithin Cholesterol acyltransferase***
48
-Bound to Lipoprotein (HDL)
- Transfer FA from C2 of phpsphatidylcholin to cholesterol
Lecithin Cholesterol acyltransferase
49
What does ACAT stand for?
Acyl-CoA:Cholesterol acyltransferase***
Acyl-CoA + Cholesterol <-------> CoA + Cholesterol ester
50
How is cholesterol esterified?
1. Lecithin cholesterol acyltransferase (LCAT)
2. Acyl-CoA:Cholesterol acyltransferase (ACAT)
51
-Esterification of cholesterol by LCAT: _______
-Hydrolysis of cholesterol: ______
plasma
liver
52
What do TG consist of?
glycerol esters combined with three FAs
-constitutes majority of "neutral fats"
53
________ from adipose tissue and are the main storage from of fats.
TGs
54
How is fat used for energy during fasting or between meals?
Stored TGs can be catabolized into FFA
55
Plasma TG are derived from the...
intestine and liver
-intestinal TG is absorbed from dietary fat
56
What is the main source of plasma TG?
liver manufacture
57
What is the difference between vegetable TG and meat TG
veg-more unsaturated FA
meat- more sat FA
58
sugar-containing lipids
Glycolipids
(cerebroside: ceramide with a sugar at the 1-OH moiety).
59
What are two groups of glycolipids?
✓ Gangliosides—major membrane lipids of CNS
✓ Membrane glycosphingolipids—important for cell recognition
and blood typing
60
-Long-chain polyunsaturated FA (eicosanoids) with C20, including a
cyclopentane ring
* Synthesized in many tissues from arachidonic acid & other
polyunsaturated fatty acids
prostaglandins
61
What are the major classes of prostaglandins?
PGA --> PGI with subscripts indicating number of C=C double bonds PGA2
62
Prostaglandins and related compounds (thromboxanes, leukotrienes) are potent, and can alter the function of
both synthesizing and adjoining cells (very strong but short half life, regulator functions)
63
Chemical cell communication
Function like Hormone, but not hormone
Not stored , but synthesized as needed (short half-life)
prostaglandins
64
What are the three phases of lipid transport though the body?
-Digestive phase (intra luminal phase)
- Absorptive phase (cellular phase)
- Transport phase
65
Why must fats be "processed" for absorption?
fats are insoluble
66
Most fats are first emulsified by the action of ________.
bile salts
-then get acted upon by pancreatic enzymes, lipase, cholesterol esterase
67
How are cholesterol esters converted to free cholesterol & free fatty acids?
lipase, cholesterol esterase
68
Digestive phase:
Phospholipids are converted into...
other derivatives (lyso-derivatives)
[(phospho)lipase]
69
Digestive phase:
The micelles are complexes of...
MG, DG,, FFA, free cholesterol, phospholipids and bile acids.
70
What are the steps of the absorptive phase?
-Micelles come in contact with mucosal cells of the intestine
* MG & FA enter the ER of the mucosal cell, presumably by
diffusion
* Smaller FFA (<10 C) pass directly into portal circulation & attach to albumin
* In the intestinal cells, FFAs are re-esterified to form TG & CE (reassembled)
* Lipids are then packaged into chylomicrons for transport in the circulation
71
2% of Lipoproteins that shows dietary intake of TG
chylomicrons
72
What is the major protein in chylomicrons?
APO B-48
73
- large water soluble lipid-protein complexes of
phospholipid, TG, & cholesterol surrounded by a protein shell
***TG RICH
Chylomicrons
74
transport phase:
Mucosal cells release __________ into abdominal lymphatics
chylomicrons
(several hrs after meal, reverse pinocytosis)
-Chylomicrons enter the systemic circulation
-Carried via bloodstream to the liver & other tissue for use/metabolism
75
How long should someone fast when getting endogenous TG tested for?
10-14
76
Where do chylomicrons get transported to?
to all tissues (including adipose tissues, the principle site of uptake)
77
Transport phase:
TG are off-loaded & catabolized at extra-hepatic sites under influence of...
TG (lipoprotein) lipase (LPL)
TG-derived FFA may be stored or used for energy
* A TG remnant remains (a TG- poor, cholesterol-rich, highly atherogenic lipoprotein); removed by liver (as TG offloads, ration changes)
78
What is lipid used for?
* Metabolic fuel
* Synthesis into other material
* Complexed into specific lipoprotein carriers by the liver for transport to other parts of the body for use
79
How is lipid stored? ***
-Excess TG stored in adipose tissue
-Excess cholesterol excreted as bile salt
80
How is lipid synthesis regulated?
by feedback regulation by free cholesterol ---->>>>> HMG-CoA reductase
81
Lipids synthesized in liver, intestines, and other tissues
* Primary site of endogenous lipid production is the _______.
liver
82
Liver also produces apolipoproteins, which
are then packaged with newly formed TG,
phospholipids, & cholesterol to form the _____
VLDL
83
What carries endogenous TG?
What carries exogenous TG?
VLDL
chylomicron
84
Chain growth during FA synthesis takes place via successive additions of two carbon units (carboxylation), derived from “__________” ---> Allow four carbon intermediates (third carbon is lost as CO2 during each cycle
malonyl CoA
85
***What is the key rate limiting step of fatty acid synthesis?
Formation of Malonyl-CoA from acetyl Co-A
86
***What is the rate limiting enzyme in fatty acid synthesis?
Acetyl CoA Carboxylase!
87
What increases Acetyl CoA Carboxylase? and what inhibits?
citrate
long chain Acyl CoA
88
B/C the bulk of acetyl CoA is formed in the mitochondrion, it has to
be transported to the cytosol in the form of _______ in order to become
a building block of fatty acid biosynthesis.
citrate
89
8 acetyl CoA molecules are used for the synthesis of one molecule of palmitate. This process also yield 8 NADPHs via the ____ enzyme reaction
malic
90
a total of 14 molecules of NADPH are needed for the synthesis of one molecule of palmitate.
* The additional NADPH are derived from...
the Pentose-Phosphate pathway
91
What does the reaction catalyzed by fatty acid synthase produce?
palmitate
92
What is not the rate limiting enzyme for FA synthesis?
Fatty acyl-CoA synthase (long term regulation?)
93
Fatty acyl-CoA
synthase and acetyl CoA carboxylase:
What all enhances enzyme synth?
-High carbohydrate diet
-Fat free (low fat) diet
94
Fatty acyl-CoA
synthase and acetyl CoA carboxylase:
What all decreases enzyme synth?
-High fat diet
-fasting
-glucagon
95
acetyl CoA carboxylase:
What agents cause allosteric activation? Enhancement?
citrate
insulin, dephosphorylation
96
acetyl CoA carboxylase:
What agents inhibit?
long chain acyl CoAs (allosteric inhibition)
glucagon, Phosphorylation (cAMP)
97
What is one of the most commonly occurring fatty acids?***
Palmitic acid
98
What is linked to ATP production?
-NADH + H+
-FADH2?
99
How do long chain fatty acids get into the mitochondria?***
Carnitine Acyltransferase
100
How are FAs of different chain sizes transported into membrane?
-short chain (2-4): free diffusion
-Medium (4-12): diffusion
-long chain (12-20): carnitine cycle
-very long chain (>20): unknown
101
What chain size of FAs can diffuse inside the mitochondria?
short and medium
102
When does beta oxidation take place?
-even number of carbons and it is saturated
103
NADH and FADH2 is produced from _________ and the TCA cycle.
oxidation
104
In Beta oxidation, what does the delta symbol mean?
the location of the double bond
105
beta oxidation:
What is detached in each cycle?
Acetyl-CoA
106
What does alternative FA oxidation pathway do?
moves the FA to trans position
a double bond on beta prevents oxidation, isomerase overcomes this by moving to trans to do beta oxidation
107
) Oxidation of unsaturated FA require additional enzymes and results in...
lower energy yield (2 ATP less/double bond)
-Each double bond is not
able to generate FADH2
108
rare reaction that moves one carbon out
alpha-oxidation
109
Oxidation of phytanic acid requires
alpha-oxidation
mitochondrial α-hydroxylase
110
a deficiency of mitochondrial alpha-hydroxylase
Refsum’s disease
-Autosomal recessive neurological disease
111
How are odd numbers of carbon fatty acids oxidized?
carbon gets added to the last metabolite
112
What sample type is used for measuring lipoproteins?
serum or whole blood
113
The liver only makes ________ , it becomes smaller after TG offloading to become LDL.
VLDL
114
____________ are the structural elements in the amphipathic shell of
lipoprotein particles
Apolipoproteins
-Apolipoproteins are complexed with lipids to form lipoproteins, which are
then soluble
115
What are the functions of apolipoproteins?***
-structural integrity of the complex
-solubility of the complex
-activate important enzymes in the lipoprotein metabolic pathways
*Facilitate the uptake of lipoprotein into cells through their recognition by
specific cell surface receptors
116
Different Apos require their __________ receptors
specific
117
Major apo of HDL; structural protein, activates LCAT; ligand for HDL binding
Apo A-I *
118
Structural protein in HDL; activates LCAT; enhances hepatic TG lipase activity
APO A-II*
119
Large major structural protein in VLDL & LDL; two forms
Apo B*
120
What are the two Apo B forms?*
✓ Apo B-100 synthesized in liver—found on VLDL, IDL, LDL
✓ Apo B-48 in the intestine—Found on chylomicrons
121
Binds to LDL receptor & (chylomicron) remnant receptor; several isoforms
Apo E***
122
What is included in Apo E
LDL, VLDL, & apo E-HDL*
iso-forms ---> E2, E4, E3 (E2 worst for cholesterol and E3 being the best, know the order)
123
Structural protein for Lp(a); highly glycosylated apo; may inhibit plasminogen binding
Apo (a)
124
*Exogenous hyperlipemia:
elevated lipoprotein:
elevated lipid class:
chylomicron
triglycerides
125
*hypercholesterolemia:
elevated lipoprotein:
elevated lipid class:
LDL
cholesterol
126
*Combined hyperlipidemia:
elevated lipoprotein:
elevated lipid class:
LDL, VLDL
cholesterol, triglycerides
127
*Remnant hyperlipidemia:
elevated lipoprotein:
elevated lipid class:
beta-VLDL
triglycerides, cholesterol
128
*Endogenous hyperlipemia:
elevated lipoprotein:
elevated lipid class:
VLDL
triglycerides
129
*Mixed hyperlipemia:
elevated lipoprotein:
elevated lipid class:
VLDL, chylomicrons
Triglycerides, cholesterol
130
Ultracentrifugation results in separation based on _______ (VLDL, LDL,
HDL, etc.)
density
131
Electrophoresis is typically performed on...
agarose or cellulose
-Barbital buffer
*Stain with fat stain
132
Where do proteins stop on electrophoresis?
isoelectric point based on the proteins unique negative charge
133
Where will chylomicrons be seen on electrophoresis?
at the aspiration band (where it is loaded?)
mostly TG; very little protein; no electrophoretic
mobility; may not be present*
134
On electrophoresis, what side do the proteins move towards?
the positive end (proteins are negative)
-Results in band at point of application (sometimes), a beta band, a pre-beta band and an alpha band
135
Alpha band...
-fastest-mostly HDL *
136
Pre-beta band...
mostly TG, VLDL*
137
Beta band...
largest percentage of lipoproteins; mostly cholesterol, mostly LDL*
138
What is the order of lipoprotein separations by ultracentrifugation?
-Chylomicrons
* VLDL-Very Low Density Lipoproteins
* IDL-Intermediate Density Lipoproteins
* LDL-Low Density Lipoproteins
* HDL-High Density Lipoproteins
139
What is important for reverse cholesterol transport pathway?
HDL
140
-Densities of lipoproteins from ultracentrifugation of the serum
-Density unit is expressed as a Sf
Flotation units: Svedberg units?
141
Low density =_________ Sf units = float (lighter, more lipid)
High density = ________ Sf units = sink (heavier, more protein)
higher, low
142
What are the Lipoprotein Transport Pathways?
-exogenous pathway
-endogenous pathway
-reverse cholesterol pathway
143
Lipoprotein Transport Pathway:
transports dietary lipids via chylomicrons from the small intestine to the liver
Exogenous pathway
144
Lipoprotein Transport Pathway:
transports hepatic lipids via VLDL and LDL to the peripheral tissues
Endogenous pathway
145
Lipoprotein Transport Pathway:
transports cholesterol via HDL from peripheral tissues back to the liver
for excretion or reuse
Reverse cholesterol pathway
146
***What are the reverse cholesterol pathway steps?
1. HDL (empty) produced in mainly the liver
2. In the intestine, HDL binds free cholesterol from peripheral cells (macrophages)
3. Cholesterol esterified by LCAT
4. Cholesterol ester delivered to liver (for eventual excretion), several mechanisms
147
Step #4 of reverse cholesterol pathway, what are the several mechanisms that cholesterol ester delivered to liver?
✓ Direct uptake of HDL by liver via apo A
✓ Apo E-containing HDL binds LDL receptor or remnant receptor
✓ HDL exchanges cholesteryl ester to VLDL/LDL for TG
-CETP: cholesteryl ester transfer protein
148
HDL assembly is from __________ and ____________ sources.
cellular, intravascular
149
HDL from largest to smallest
2B, 2A, 3A, 3B, A-1
150
What is the importance of lipoprotein receptors?***
-Necessary for delivering lipoproteins to cells
-Necessary for efficient removal of potentially atherogenic
lipoproteins from the blood and peripheral tissues
151
Lipoprotein Receptors:
APO B-100 and APO E
▪ Cell binding
▪ Uptake and degradation of LDL
▪ Synthesis inhibited by high cholesterol level
▪ Defective receptors stimulates intracellular cholesterol synthesis
LDL Receptors
152
Familial hypercholesterolemia :
_____ % of LDL receptor defective
50
153
Lipoprotein Receptors:
-APO E
-Clearance of chylomicron and β-VLDL remnants from blood circulation
Remnant Receptors
154
Lipoprotein Receptors:
Surface of macrophage and muscle cells
▪ Mediate removal of modified LDL from blood circulation
▪ Macrophage with high cholesterol accumulation: Foam cells
Scavenger Receptors
155
Understand that excess citrate goes to _____________ synthesis.
fatty acid
156
What is the #1 cause for disability and #4 for death?
stroke
-CV disease is the leading cause of death in western
population
* Lipids deposit in vessels over time cause an
occlusion
* An increase in fats from either dietary intake or an
increase in endogenous production may result in
arterial plaque formation
157
What is the process that leads to occlusion?
Macrophage --> Foam Cells ---> Fatty Streaks (previously damaged areas) --> Future injury ---> More damage --->Plague formation---> Narrow vessel lumen ---> Occlusion
158
What is in a lipid profile?
(1)Total and HDL cholesterol, with measured or calculated LDL cholesterol; (2)
Triglyceride determination; (3) lipoprotein electrophoresis
159
What is the relationship between HDL cholesterol and coronary risk?
inverse relationship
160
How do you calculate LDL/HDL Cholesterol Risk Ratio?***
✓ VLDL= TG/5
✓ LDL = total cholesterol-VLDL-HDL
LDL/HDL***
161
When can the LDL/HDL risk ratio not be used? ***
-chylomicrons are present
-serum triglyceride is greater than 400 mg/dl
162
LDL/HDL Cholesterol Risk Ratio for MALES:***
One-half average:
average:
twice average:
three times average:
One-half average: 1.00
average: 3.55
twice average: 6.25
three times average: 7.99
163
LDL/HDL Cholesterol Risk Ratio for FEMALES:***
One-half average:
average:
twice average:
three times average:
One-half average: 1.47
average: 3.22
twice average: 5.03
three times average: 6.14
164
Cephalins and lechithin have what backbone
Glycerol
165
CAD or CHD
Plaque formation in the heart is coronary heart disease (CHD) or
coronary artery disease (CAD)
166
PVD
Plaque formation in the arms and legs is peripheral vascular
disease (PVD)
167
CVD
Plaque formation in the brain causes cerebrovascular disease
(CVD)
