Lipids Flashcards
(131 cards)
1
Q
What are the general functions of lipids?
A
- Storage
- Transport
- Structural component
- Energy production
2
Q
What is the function of fatty acids?
A
metabolic fuel, building block for other lipids
3
Q
What is the function of Triacylglycerol?
A
Storage, transport of fatty acids
* They are not found in cell membranes
4
Q
What is the function of ketone bodies?
A
fuel for skeletal muscles, brain, kidney and cardiac muscle
5
Q
What is the function of cholesterol?
A
precursor of bile acids, steroids, Vit D. Also a structural component
6
Q
What is the function of sphingolipids?
A
Structural component and surface antigen
7
Q
What is the function of phospholipid?
A
Storage of polyunsaturated fatty acids, signal transduction. Also a building block for membranes
8
Q
Fatty acids are composed of ….?
A
Long hydrocarbon chains (aliphatic) with a carboxyl group at one end
- The carbon next to the carboxyl group is alpha carbon
- Fatty acids are amphipathic molecules (having both polar and non polar ends)
9
Q
What are the numbering system for fatty acids?
A
- C-system: starts at the carboxyl group
2. ω-system, omega starts at the methyl end
10
Q
The difference between saturated and non saturated fatty acids is …..
A
the presence or absence of double bonds, respectively.
* The most common saturated fatty acids are stearic (C18) and palmitic (C16) acid
11
Q
Monounsaturated fatty acids have ….. bonds
A
one double. like oleic acid
12
Q
Polyunsaturated fatty acids have ….. bonds
A
two or more double. Like linoleic and linolenic acid
* linolenic and linoleic fatty acids are essential fatty acids
13
Q
Arachidonic acid has ….. double bonds. It is synthesized from linoleic acid in humans. It is a ….. carbon & …… fatty acid
A
four
20 carbon, 6-omega
* if Linoleic acid is deficient, arachidonic acid becomes essential fatty acid
* Deficiency of essential fatty acid (linoleic and linolenic) is seen in patients being fed intravenously with no fat supplementation
14
Q
Arachidonic acid is a major precursor for ……
A
prostoglandins, thromboxane and leukotrienes
* Platelet aggregation is controlled by antagonistic effect of thromboxane and prostoglandins
15
Q
Eicosanoids are ………. . They include …., ….. , …..
A
signal transduction molecules for the control of inflammation and immunity
Prostoglandin, thromboxane and leukotriene
* They are derived from arachidonic acid
* They have short half lives
16
Q
In triacylglycerols, fatty acids are linked as ….. to a glycerol back bone. They are transported in plasma by …..
A
esters
lipoproteins
* Increased levels is linked to atherosclerosis, heart disease and stroke
17
Q
Diacylglycerol act as a secondary messenger in ……..
A
phosphatidylinositol signal transduction pathway
18
Q
2-monoglyceride is the end product of ………
A
TAG digestion in small intestine
19
Q
Ketone bodies have …… or ….. attached to beta carbon atom
A
hydroxyl or keton
20
Q
Ketone bodies are synthesized from ….. and ….. in liver during starvation
A
aminoacids and fatty acids
21
Q
A steroid nucleus is ……
A
a fused four member ring system that contains 19 carbon atoms
22
Q
Cholesterol is a ….. carbon compound, is the precursor for Vit D
A
27
- Vit D (C27)
- bile acid (C24)
- adrenocortical hormone (C21)
- progesterone (C21)
- androgens (C19)
- estrogens (C18)
23
Q
Why phospholipids are amphipathic?
A
It has hydrophobic and hydrophilic components.
* They consist of two fatty acids connected as esters to glycerol, and phosphate group connected to the third carbon on the glycerol. The hydrophilic head (phosphate), hydrophobic head (fatty acids)
see p.324
24
Q
Respiratory distress syndrome is caused by inability of the lung to produce ……..
A
dipalmitoylphosphatidylcholine, the active component of the surfactant.
- Symptoms include acidosis, hypoxia
- Tx is with glucocorticoids to induce the surfactant production and development of the lungs
25
Ceramide is composed of ......
sphingosine, which is a long chain of amino alcohol with a saturated fatty acid linked to the amino group
see p.325
26
Sphingolipids and glycolipids contain ...... as a structural component.
ceramide
27
What is the difference between cis and trans fats?
In trans configuration, the carbon chain extends from opposite side of double bond straightly. While in cis, the carbon chain extends from the same side of the double bond, rendering a bent molecule
28
The main vehicle for transporting lipids is .........
lipoproteins
29
Lipoproteins consist of ........ and a .......
1. hydrophilic shell: made of proteins, phospholipids, unesterfied cholesterol
2. Hydrophobic core: made of cholesterol ester, triacylglycerol and neutral lipids
* Lipoproteins are bound to a protein moiety (apoprotein)
30
The different classes of lipoproteins can be separated by what method?
electrophoresis (size and charge) or centrifugation (on basis of density)
31
Define the chylomicrons and state its function and where it is synthesized
they are the largest and the least dense lipoproteins, and don't migrate in electric field (neutral)
Synthesis occurs in the smooth ER of intestinal cells.
They transport TAG and cholesterol esters from intestine to different parts of the body
32
Define VLDL and state its function and where it is syntesized
like chylomicrons. Synthesized by the liver and transport TAG and cholesterol esters to adipose tissue.
* Lipoprotein lipase degrades VLDL to smaller molecules of lower density which can be internalized by the liver
33
Define LDLs and state its function
Generated by the action of Lipoprotein lipase on IDL. The major function is to transport cholesterol to extrahepatic tissues where it is taken by endocytosis (macrophage)
34
Define HDLs and state where it is synthesized
Synthesized by the liver, and composed of %50 protein with its core region empty
* It collects cholesterol from the body and return it to the liver
35
What are the functions of HDL?
1. Remove cholesterol from the cells, esterify it to cholesterol esters and move it back to the liver
2. Circulating reservoir for apolipoproteins
36
Fatty acids released from adipose tissues to skeletal and cardiac muscles and the liver are carried by ......
albumin
| * They undergo beta-oxidation for energy
37
Fatty acid metabolism is controlled largely by the ........ ratio
insulin/glucagon
* High ratio: favors lipid synthesis and storage
* Low ratio: mobilization and beta oxidation
38
Excessive oxidation of fatty acids leads to accumulation of ......... , which is converted to soluble ....... to provide energy for other tissues
AcetylCoA, ketone bodies
39
The requirements for fatty acid synthesis are
NADPH, AcetylCoA, bicarbonate, ATP, biotin
40
Fatty acid synthesis is the reversal of beta oxidation except .... and .....
the difference in enzymes and reaction location
* Beta oxidation: in the mitochondria
* Fatty acid synthesis: cytosol
41
Before fatty acid synthesis occur, Acetyl-CoA must be moved to the cytosol by .....
citrate shuttle
| * the mitochondrial membrane is impermeable to AcetylCoA
42
In the mitochondria, citrate is formed by ..... and .....
AcetylCoA and oxaloacetate
43
Citrate shuttle is cleaved in the cytosol by the enzyme ....... yielding ...... and .......
1. citrate lyase
2. oxaloacetate and AcetylCoA
* in the cytosol, oxaloacetate is converted to malate, then to pyruvate (catalyzed by malate decarboxylase). Only then it can return into the mitochondria
44
NADPH is produced mainly form the HMP, and to a lesser degree from ......
citrate shuttle
45
The first reaction in fatty acid synthesis is the conversion of acetyl-CoA into ........ which is catalyzed by .........
1. malonyl-CoA
2. Acetyl-CoA carboxylase
* This reaction requires biotin and bicarbonate and one ATP. It is the rate limiting step
46
Define malonyl-CoA
A three carbon compound, which will serve as donor of 2 carbon units in the elongation of the fatty acid chain
47
Define fatty acid synthase, and describe its action
Multienzyme complex in fatty acid synthesis. It lengthens the fatty acyl-CoA by the addition of two carbon units to the carboxyl end. After that the product is reduced to a fully saturated acyl group
At the end of each cycle, the product is transferred onto the synthase enzyme so that the acyl carrier protein can be recharged with another malonyl and new cycle begin
* Summary of the reactions: condensation, reduction, dehydration, reduction
* CoA is pantothenic acid (vit. B 5)
48
In fatty acid synthesis, each addition of 2 carbon molecules uses ...... . And all reactions occur while the intermediate are covalently bonded by a ....... to acyl carrier protein
NADPH, thioester linkage
see p.329
49
Why elongation of fatty acid chain synthesized stops at C16 (palmitoyl-CoA)?
It needs special microsomes present in the SER to elongate past C16
50
Synthesis of palmitoyl-CoA requires ....... ATP and ...... NADPH
7 ATP, 14 NADPH
51
Elongation of palmitoyl-CoA can occur in the mitochondria. T/F
True..
| * Acetyl-CoA can be used for the elongation instead of malonyl-CoA.
52
How is the fatty acid synthesis process regulated?
By the control of the rate limiting step.
Acetyl-CoA carboxylase is activated by insulin, high carbohydrate and low fat diet.
It is inhibited by glucagon, high fat diet and fatty acids.
53
Acetyl-CoA carboxylase is activated by ..... and inactivated by .........
1. insulin dependent dephosphorylation
| 2. cAMP dependent phosphorylation
54
........ is responsible for the synthesis of both Acetyl-CoA carboxylase and fatty acid synthase complex
insulin
55
Beta oxidation of fatty acids occur in ........ and .......
mitochondria and peroxisomes
| * peroxisomes use different enzymes for oxidation of fatty acids
56
The uptake and oxidation of fatty acids involve 3 steps. What are they?
1. Activation: Traps fatty acids inside the cell. requires fatty acyl-CoA synthetase (thiolase) and one ATP. This forms a thioester linkage with CoA-SH
2. Transfer of the fatty acid into the mitochondria
3. Beta oxidation of fatty acids
57
Describe the 3 steps for the fatty acid transport into the mitochondria
1. Carnitine-acyl transferase-I (CAT-I): associated with the outer surface of the inner membrane. Transfers the fatty acid from fatty acyl-CoA to form fatty acyl-carnitine
2. Carnitine translocase: transports the fatty acyl-carnitine into the matrix and returns the carnitine.
3. Carnitine-acyl transferase-II (CAT-II): reforms fatty acyl-CoA inside the matrix
58
Why is the fatty acid degradation pathway is called beta oxidation?
because the two oxidation steps involve the beta carbon
59
Each cycle of fatty acid beta oxidation involves ....... steps and generates one ....., ...... and ......
1. four
| 2. FADH2, Acetyl-CoA, NADH
60
Beta Oxidation of fatty acids involves the removal of .....
2 carbon fragments from the carboxyl end
61
Describe the steps of beta oxidation of fatty acids
1. Dehydrogenation: forms a double bond between alpha and beta carbons and generates FADH2
2. Hydration: of the double bond to form beta-hydroxyacyl-CoA
3. Dehydrogenation: with NAD+ to generate beta-ketoacyl-CoA and NADH
4. thiolytic cleavage: by the addition of CoA-SH to the beta carbon and release of acetyl-CoA to complete the cycle.
62
Describe the fate of odd number fatty acids in beta oxidation
In the final thiolytic cleavage cycle, one molecule of propionyl-CoA is released from the omega end of the fatty acid.
Propionyl-CoA is carboxylated to methymalonyl-CoA and then converted to succinyl-CoA to enter the TCA cycle.
63
How is beta oxidation works for unsaturatd fatty acids?
an isomerase enzyme converts all cis bonds in natural fat to trans configuration, because the hydratase enzyme in beta oxidation works only on trans bonds.
64
Complete beta oxidation of palmitic acid (C16) produces ........
8 molecule of acetyl-CoA, 7 NADH, 7 FADH2
65
Define RQ (respiratory quotient)
Is the mols of CO2 produced to mols of O2 consumed.
* It is 1 for glucose oxidation in glycolysis and TCA cycle
* It is 0.7 for beta oxidation
66
The net yield of ATP from complete oxidation of palmitic acid is .....
129 ATP
67
How is the beta oxidation of fatty acids regulated??
By controlling the rate of transfer of the fatty acids into the mitochondria. CAT-I is inhibited by malonyl-CoA (first product of synthesis).
The rate of oxidation is also controlled by the rate of release of fatty acids from adipose tissue.
see p. 332
68
The two major ketone bodies are ...... and ......
beta-hydroxybutyric acid, acetoacetic acid
69
Ketone synthesis is inhibited when ...... is available
glucose
70
Ketosis is the overproduction of ketones as a result of ........ .
high glucagon/insulin ratio and low carbohydrate
| * The pH of plasma is lowered and the bicarbonate level is decreased
71
Ketone bodies are synthesized in the ...... when .......
1. liver mitochondria
| 2. glucose level is low and acetyl-CoA is abundant due to fatty acid break down
72
Ketones are formed from condensation of .......
3 acetyl-CoA molecules
* first, two are condensed to form acetoacetyl-CoA
* The third is added to acetoacetyl-CoA to form HMG-CoA (beta hydroxy-beta methylglutaryl-CoA), catalyzed by HMG-CoA synthase (rate limiting step)
* HMG-CoA is cleaved into acetyl-CoA and acetoacetate
* acetoacetate is reduced to beta-hydroxybutyrate (most common ketone)
73
Beta hydroxybutyrate is oxidized back to ...... after the uptake by cells
acetoacetate
| * Ketone bodies are both synthesized & metabolized in the mitochondria
74
Why the liver can not metabolize ketone bodies?
because it lacks the transferase enzyme
* This enzyme transfers CoA-SH from succinyl-CoA to acetoacetate to form acetoacetyl-CoA
* Thiolase cleaves acetoacetyl-CoA into two molecules of acetyl-CoA
see p.333
75
Synthesis and degradation of triacylglycerol involves the formation and hydrolysis of ....... between fatty acids and .....
1. ester bonds
| 2. glycerol back bone
76
Factors that promote lipolysis are ...... , lipogenesis are ......
1. Lipolysis: low insulin/glucagon ratio, fasting, exercise
| 2. Lipogenesis: High insulin/glucagon ratio, high carb diet
77
Glycerol phosphate can be obtained by the reduction of .......
DHAP
78
In fatty acid synthesis, fatty acids are transferred from fatty acyl-CoA to glycerol backbone by ....
transferase enzyme
* Addition of two fatty acids to glycerol forms diacylglycerol (after the removal of the phosphate from the glycerol phosphate)
* A third fatty acid is added to diacylglycerol to form triacylglycerol
see p. 333
79
Triacylglycerol hydrolysis involves different .... enzymes which differ in their specificity. What are these types?
* lipases
1. Hormone sensitive lipase: in adipose tissue. Hydrolysis the first fatty acid from triacylglycerol and is the rate limiting step
2. Pancreatic lipase: hydrolysis dietary fats. Removing 2 fatty acids from position 1 & 3 and leaving 2-monoglyceride
3. Lipoprotein lipase (LpL): in adipose and muscular tissue. It hydrolysis chylomicrons and VLDL into fatty acids and glycerol.
80
Adipose tissue can not utilize glycerol for energy because .......
they lack the enzyme glycerol kinase
* glycerol kinase converts glycerol into glycerol-3-phosphate.
* glycerol-3-phosphate is oxidized to DHAP. This in turn can be isomerized into G-3-P
81
Remnants of chylomicrons and VLDL from LpL activity are .......
high in cholesterol (IDL). They are removed by the liver for bile acids production
82
What are the major sites for cholesterol synthesis?
Liver, ovaries, testes and adrenal cortex
83
What are the substrates for cholesterol synthesis?
Acetyl-CoA, ATP, NADPH and O2
* The enzymes for the synthesis are extramitochondrial.
* 18 Acetyl-CoA+18ATP+18NADPH + 4O2 (gives) cholesterol(C27)+18NADP+18ADP+18Pi+9CO2
84
The rate limiting step in cholesterol synthesis is .........
the formation of mevalonic acid
* 3 molecules of acetyl-CoA are condensed to form HMG-CoA
* HMG-CoA is reduced with 2 NADPH to mevalonic acid (C6). The reaction is catalyzed by HMG-CoA reductase
85
The synthesis of HMG-CoA for cholesterol differs from that in ketone bodies in .....
1. requires different enzymes
| 2. cytosolic HMG-CoA pool for cholesterol synthesis is not mixed with the mitochondrial pool used for ketones
86
In the second stage of cholesterol synthesis, mevalonic acid is converted into .....
activated isoprene units (C5) that are designed to condense with each other
87
What are the two types of activated isoprene ?
Isopentenylpyrophosphate (IPP) and dimethylallylpyrophosphate (DPP)
* the synthesis of activated isoprene requires 3 ATP
88
In the third stage of cholesterol synthesis, ....... which is a C30 compound is formed
squalene
* it is formed from condensation of 6 activated isoprene units
* IPP + DPP (gives) geranyl pyrophosphate (C10)
* Geranyl pyrophosphate + IPP (gives) farnesyl pyrophosphate (C15)
* two farnesyl is condensed to form squalene
see p.335
89
The fourth stage of cholesterol synthesis involves the cyclization of squalene to form .......
lanosterol
| * Lanosterol is converted by a series of reactions into cholesterol
90
%70 of the cholesterol found in humans is .......
cholesterol esters
91
What is the function of pancreatic cholesterol esterase?
Hydrolyzes the dietary cholesterol esters in the intestine.
| * Re-esterification occurs upon diffusion into the cells, but before incorporation into the chylomicrons
92
Intracellular cholesterol esterase is found in ......
all tissue, but most prominent in the liver
93
What are the two enzymes involved in cholesterol esters synthesis?
1. Lecithin cholesterol acyltransferase (LCAT): removes cholesterol from plasma and package it in HDL
2. Acyl cholesterol acyltransferase (ACAT): found inside the cells. Aids in storage of cholesterol
94
Diets high in fat and carbohydrates stimulate ...... enzyme, which lead to increase cholesterol synthesis
HMG-CoA reductase.
| * Synthesis of cholesterol is stimulated by insulin and thyroxine by increasing HMG-CoA activity
95
To inhibit HMG-CoA reductase activity, we need to limit the availability of ........ and ........
acetyl-CoA and NADPH (fasting)
| * Glucagon inhibits HMG-CoA reductase activity
96
Cholesterol is constantly recycled between the liver and other tissues. T/F
True
97
Each of the four reactions of bile acid synthesis makes them more ......
amphipathic and more suitable for lipid emulsification
98
Bile acids are the major excreted form of ......
cholesterol
99
Summarize the four reactions for bile acid synthesis
1. side chain cleavage releasing three carbon atoms and forming C24 carboxylic acid compound
2. Conjugation: of side chain carboxyl with glycin or taruin to ensure complete ionization at physiologic pH
3. Reduction of double bond in the ring system with NADH
4. Hydroxylation at carbon 7 and 12 with both O2 and NADPH
100
What does the term bile salt mean?
mean that the side chain is associated with a counter ion
101
The rate limiting step in steroid hormone synthesis is ......... by .........
cleavage of cholesterol side chain to generate pregnenolone (C21) by the enzyme 20-22 desmolase
102
The activity of Desmolase is located in the ..........
mitochondria
* responsible for side chain cleavage of cholesterol in steroid synthesis
* Its activity is increased by hormones
103
Pregnenolone is converted to progesterone by action of ........
3-beta-hydroxysteroid dehydrogenase
| * Both pregnenolone and progesterone are C21 intermediates in steroid synthesis
104
What is the hormone that control the synthesis of each of the following steroids:
1. glucocorticoids
2. mineralocorticoids
3. androgens and estrogens
1. ACTH
2. angiotensin II
3. LH
* Each of these hormones increase desmolase activity
105
In the adrenal cortex, cortisol synthesis requires the hydroxylation of ........., while aldosterone synthesis requires the hydroxylation of .........
11,17,21 carbons
| 11,18,21 carbons
106
Cleavage of the steroid nucleus side chain by the enzyme 17-20 desmolase produce .........
androgen C19
107
5-alpha-reductase enzyme reduces the double bond in ........ to form .......
testosterone, DHT
| * This enzyme is available in all tissues utilizing DHT
108
What is the function of the aromatase enzyme?
removes the methyl group connecting the A and B rings on the steroid nucleus and makes the A ring aromatic
* Aromatase presents in all tissues converting androgen to estrogen
109
What are the substrates required for the synthesis of phophatidylethanolamine in phospholipids?
ethanolamine and diacylglycerol
* ethanolamine is first phosphorylated with ATP, to form ethanolamine-P
* Then it is condensed with cytidine-p-p-p to form cytidine-5-diphosphate-ethanolamine
* The transfer of P-ethanolamine from CDP-ethanolamine to the free hydroxyl of diacylglycerol to form phosphatidylethanolamine
* It is a nerve tissue component
see p.338
110
Decarboxylation of phosphatidylserine results in ..........
phosphatidylethanolamine
111
Methylation of phosphatidylethanolamine with 3 molecules of S-adenosylmethionine (SAM) results in the formation of ........
phosphatidylcholine (lecithin)
* It is a plasma membrane component
* Important for sufactant formation
* Necessary for the formation of acetylcholine (neurotransmitter)
* Important for the release of VLDL from the liver.
see p. 339
112
All sphingolipids are considered glycolipids except .........
sphingomyelin
| * they are considered glycolipids due to presence of carbohydrate.
113
The first step in the synthesis of sphingolipids is ...........
formation of ceramide core
114
The ceramide core of sphingolipids is formed by ....., ...... & .....
palmitoyl CoA, serine, long chain fatty acyl CoA
115
Sphingomyelin is formed by transfer of ....... from ...... to ceramide. It is found in .......
phosphocholine, UDP-choline
| Found in membranes of CNS
116
Cerebroside contain .... & ...... .
glucose, galactose
117
Sulfatides are formed by addition of ....... to ......., in a reaction that requires .....,..... & ......
sulphate to galactosecerebroside
| UDP-glucose, UDP-galactose & PAPS
118
Globosides are found in ...... . Formed by addition of ..... , ...... or ...... to ceramide
RBC
| glucose, galactose or N-acetylgalactoseamine
119
Gangliosides are found in ........... . They contain .........
```
ganglion cells of the CNS
neuraminic acid (form of sialic acid)
```
120
Prostaglandin is a ....... carbon fatty acid, containing a 5 membered ring. PGI2 (prostacycline) is a major prostaglandin, synthesized by ..... with the function ......
20
| endothelial cells. vasodilatation of arteries and antiplatelet aggregation
121
Thromboxane is a ....... carbon fatty acid, containing a ....... ring. Thromboxane A2 is the most common, synthesized by platelets to antagonize the action of ......
20, 6 membered ring
| PGI2 (which leads to vasoconstriction and platelet aggregation)
122
Leukotrienes have ...... ring. SRS-A is a major leukotriens with the function of ...... & .....
no rings
SRS-A (slow reacting substance of anaphylaxis) is a mix of leukotriens that have a potent vasoconstriction effect
* Leukotrienes also play a role in chemotaxis
123
Arachidonic acid is stored in ..........
membrane phospholipid where it is esterfied to carbon-2 of the glycerol back bone.
* Released from phospholipid by phospholipase A2
124
Phospholipase A2 release is inhibited by ......
glucocorticoids
| * cortisol inhibits immune & anaphylactic reactions by this method
125
Cyclooxgenase catalyzes .....
conversion of arachidonic acid to prostoglandins and thromboxanes
* Irreversibly inhibited by NSAIDs (by acetylation of serine)
126
Lipooxgenase catalyzes the reaction ......
that converts arachidonic acid to leukotrienes
127
Describe the phosphatidylinositol pathway
Diacylglycerol is activated to CDP-diacyglycerol. DAG-phosphate is then transferred from CDP-DAG to the hydroxyl in of inositol
128
All classes of sphingolipids & glycolipids are synthesized by .....
Transfer of groups from their activated carrier to a hydroxyl on terminal carbon in ceramide
129
Hormone sensitive lipase must be ..... in the cell by protein kinase A before it becomes active
phosphorylated
130
Acetoacetate is a ...... carbon keto acid
4 carbon
| * It decomposes to acetone (3 carbon) & CO2
131
The most common fatty acid found esterified to cholesterol is .....
Oleic acid
