Lecture 4- Lipids To Cholesterol Flashcards
(153 cards)
1
Q
What organic molecule in the body contains the largest source of energy?
A
Lipids
2
Q
Where does the digestion of lipids begin? what catalyzes it? And what are the primary targets?
A
Begins in the stomach
Lipase
Targets Triacylglycerols (TAGs)
3
Q
Where does the emulsification of dietary lipids take place?
A
Duodenum (small intestine)
4
Q
What does emulsification of dietary lipids achieve? And what does the emulsifying?
A
It increases the surface area of the hydrophobic lipid droplets so that the digestive enzymes can act effectively.
Bile salts do it
5
Q
What degrades dietary lipids?
A
Pancreatic enzymes
6
Q
What degrades TAG (triacylglyceride)?
A
Pancreatic lipase
7
Q
What degrades cholesterol esters?
A
Cholesteryl esterase
8
Q
What degrades phospholipids?
A
Phospholipase A2
Lysophospholipase
9
Q
Why are TAGs unable to efficiently be taken up by the mucosal cells of the intestinal villi?
A
TAGs are too large
10
Q
What acts on TAGs to make them smaller, what is being removed and what is the end product?
A
Pancreatic lipase
Removes the fatty acids (FAs) from C1 and C3
Forms 2-monoacylglycerol
11
Q
What form are most dietary cholesterol present in?
A
Free form (nonesterified)
12
Q
What enzyme hydrolyzes cholesterol esters, what factor affects the enzyme, and what is the final product?
A
Cholesteryl esterase hydrolyzes the ester bond and releases a fatty acid.
It’s activity is greatly increased in the presence of bile salts.
Cholesterol is the final product
13
Q
What type of backbone do phospholipids have?
A
Glycerol backbone
14
Q
What enzyme removes a FA from the C2 of a phospholipid?
A
Phospholipase A2
15
Q
What enzyme removes a FA from C1 of a phospholipid?
A
Lysophospholipase
16
Q
What is the product when phospholipase A2 acts on a phospholipid?
A
A lysophospholipid
17
Q
What is the product when lysophospholipase acts on a lysophospholipid?
A
Glycerophosphoryl base
18
Q
What are two hormones produced by gut cells that aid in lipid digestion and what are their responses?
A
Cholecystokinin (CCK)- causes pancreas to secrete pancreatic enzymes, gall-bladder to secrete bile, and makes the stomach feel fuller longer
Secretin- causes the pancreas to secrete bicarbonate
19
Q
What is the name of an intestinal mucosal cell?
A
Enterocyte
20
Q
What forms mixed micelles and what are they?
A
Lipids, bile salts and fat soluble vitamins
Disk shaped clusters of amphipathic lipids that coalesce with their hydrophobic groups on the inside
21
Q
Where is the primary site for lipid absorption?
A
The brush border membrane of the enterocytes
22
Q
Where are the absorbed lipids in enterocytes resynthesized back to complex lipids (original forms)?
A
Endoplasmic reticulum of the enterocytes
23
Q
What can lipid malabsorption result in?
A
Steatorrhea- lipid in feces
Caused by disturbances in lipid digestion and/or absorption
24
Q
Chylomicron
A
A lipid droplet composed of an aggregate of resynthesized
TAGs and
cholesteryl esters, surrounded by phospholipids
Unesterified cholesterol, and
Apolipoprotein
25
How and where are chylomicrons released from enterocytes?
Released by exocytosis into the lacteals (lymphatic vessels originating in the villi of the small intestine)
26
What is the path of chylomicrons and its component parts?
Exits the enterocyte and enters into the lymph, then enters blood via the thoracic duct into the sublavian vein, TAGs are drawn off my muscle and fat cells, chylomicron remnants are removed from the blood by the liver.
(Don't enter blood directly cuz too large)
27
TAGs contained in chylomicrons are broken down primarily where and by what?
In skeletal muscle and adipose tissue by
| Lipoprotein lipase
28
Explain fatty acids
Produce energy
| Resynthesized to TAGs which are stored until FAs are needed
29
Explain glycerol use in the body
Used almost exclusively by liver to produce glycerol-3-phosphate which can enter glycolysis or gluconeogenesis by oxidation to DHAP
30
Explain what happens to remaining chylomicron components
Taken up by liver and hydrolyzed to their component parts
| Some can be recycled by the body
31
Fatty acid forms found in the body
Free fatty acids
| Fatty acyl esters in TAGs
32
What tissues can particularly oxidize fatty acids to produce energy?
Liver
| Muscle
33
Note which carbon in a fatty acid chain is the alpha carbon
C2, not the 1st carbon in the carboxyl group
34
What does a fatty acid consist of?
A hydrophobic hydrocarbon chain with a terminal hydrophilic carboxyl group
* amphipathic molecule
35
At pH of 7, is the hydrophilic carboxyl group of a fatty acid ionized or not ionized?
Ionized
36
What form are the majority of fatty acids in when found in plasma?
90%+ are fatty acid esters (primarily TAG, cholesteryl ester and phospholipid)
37
Unesterified (free) fatty acids are transported in the circulatory system in association with what?
Albumin (water soluble protein)
38
How long are fatty acids?
Typically between 12 and 20, but could be longer
39
How are fatty acids numbered?
Starting with the carboxylate end
40
Saturated vs unsaturated fatty acid
```
Saturated = no double bonds (completely reduced)
Unsaturated = at least 1 double bond
```
41
The double bonds in fatty acids are most commonly (cis/trans)? And which type packs tighter? And which type causes a "kink"?
Cis is more common
Trans pack tighter
Cis cause a kink
42
Which fatty acids have a lower melting point, cis or trans?
Cis have lower melting point
43
What happens to the melting point as the hydrocarbon chain lengthens?
Melting point increases
44
Multiple double bonds in a fatty acid exhibit what type of spacing?
Spaced at 3-carbon intervals
45
Arachidonic acid
20:4 (5,8,11,14)
Explain what it means
20 carbons long
| 4 C=C between C5-6, C8-9, C11-12, C14-15
46
```
Another way to write
18:2 (9,12) and general class name
```
18:2w-6
Omega-6 fatty acid
w = omega
47
What are the essential fatty acids?
Linoleic acid
| a-linolenic acid (extra dbl bond)
48
What are lipids?
Heterogenous group of hydrophobic organic molecules
49
What are linoleic acid and its derivatives referred to as?
Omega-6 fatty acids
50
What are a-linolenic acid and its derivatives referred to as?
Omega-3 fatty acids
51
What happens to carbohydrates and proteins obtained from the diet that are in excess of the body's needs?
Converted to fatty acids and stored as triacylglycerols
52
In adults, where does fatty acid synthesis occur?
Liver (mainly)
Lactating mammary glands
Adipose tissue (to a lesser extent)
53
Where does fatty acid synthesis synthesis occur?
Cytosol
54
During fatty acid synthesis, where do the carbons come from that are incorporated into the growing fatty acid chain?
Carbons from acetyl- CoA
| by using ATP and NADPH
55
How are fatty acids synthesized?
By the repetitive addition of two-carbon units to the growing end of the hydrocarbon chain
56
How is acetyl-CoA in the mitochondrion transported to the cytosol?
Acetyl-CoA binds to oxaloacetate via citrate synthase to form citrate which crosses the membrane and is then reconverted to oxaloacetate and acetyl-CoA
57
During fatty acid synthesis, what two products are acetyl-CoA converted to and by what enzymes?
To acetyl-ACP (acyl carrier protein) by transacylase
| To malonyl-CoA by acetyl-CoA carboxylase
58
What is acetyl-ACP converted to and by what enzyme?
To acetyl-synthase by
| Transacylase
59
What is malonyl-CoA converted to and by what enzyme?
Malonyl-ACP by
| Malonyl transacylase
60
What is the first 4 carbon unit formed during fatty acid synthesis?
Acetoacetyl-ACP
61
Final product in fatty acid synthesis and what enzyme releases it?
Palmitate
| Released by FAS (fatty acid synthase)
62
Making a fatty acid is a reductive/oxidative pathway?
Reductive
63
Where does the NADPH found in fatty acid synthesis come from?
Pentose phosphate pathway
64
Palmitate, when further elongated, happens where, by what, and what is it then called?
Happens in the smooth ER
Malonyl CoA is the 2 carbon donor and NADPH supplies the electrons
Palmitic acid
65
Where does desaturation of FAs occur and what does it?
In the smooth ER
By desaturases
(Adds cis double bonds)
66
During desaturation, where is the first double bond typically placed?
Between carbons 9 and 10
67
Can mammals introduce a C=C bond beyond carbon 9?
No
68
How are fatty acids connected to glycerol?
Via ester bonds
69
How is acylglycerol classified as a fat or an oil?
Fat is solid at room temp
| Oil is liquid at room temp
70
What type are the 3 fatty acids esterified to a glycerol molecule? (Saturated vs unsaturated)
C1- typically saturated
C2- typically unsaturated
C3- can be either
71
Can TAGs form stable micelles?
No, they are only slightly soluble in water
72
What happens to TAGs within adipocytes?
They coalesce to form oily droplets that are nearly anhydrous
*major energy reserve for body
73
What is the initial acceptor of fatty acids during TAG synthesis?
Glycerol phosphate
74
What must happen to a fatty acid before it can participate in metabolic processes?
Be converted to its active form (attached to CoA)
75
What catalyzes the activation of fatty acids?
Fatty acyl CoA synthetases (thiokinases)
76
End product of glycerol phosphate and fatty acyl CoA is what? Main enzyme involved in the pathway?
TAG
| Acyltransferase
77
What is the fate of TAG in adipose tissue and in the liver?
Adipose tissue- stored in a nearly anhydrous form as fat droplets in the cytosol of cells
Liver- little is stored here. Most are exported, packaged with VLDL
78
What is the body's major fuel storage reserve?
Fatty acids stored in adipose tissue in the form of TAG
79
What are the yields from complete oxidation of fats, carbohydrates and proteins to CO2 and H2O?
Fats- 9 kcal/gram
Carbohydrates- 4 kcal/gram
Proteins- 4 kcal/gram
80
What is required for the mobilization of stored fat?
Hydrolytic release of fatty acids and glycerol from their tag form, initiated by hormone-sensitive lipase
81
What does hormone-sensitive lipase do?
Removes a fatty acid from carbon 1 and/or carbon 3 of the TAG
82
What is the major pathway for catabolism of fatty acids?
b-oxidation
83
What is b-oxidation and where does it occur?
Two-carbon fragments are successively removed from the carboxyl end of the fatty acyl CoA, producing acetyl CoA
Occurs in mitochondria
84
If a fatty acid chain is longer than 12 Carbons, what is its method for entrance into the mitochondria?
Carnitine shuttle
85
Explain carnitine shuttle
Fatty acyl CoA enters intermembrane space. Carnitine binds to fatty acid and releases CoA via carnitine palmitoyltransferase I.
Passes into mitochondria then carnitine palmitoyltransferase II adds CoA back on and releases carnitine
86
Describe b-oxidation with odd number of carbons
Proceeds normally until 3 carbons left (Propionyl CoA)
| This is metabolized to Succinyl CoA which can then enter the krebs cycle directly
87
What provides more energy, saturated or unsaturated fats?
Saturated
88
What happens to extra long fatty acids (22+ Cs)?
Preliminary b-oxidation in peroxisomes, then normal pathway to carnitine shuttle
89
Result of excess acetyl-CoA in the liver mitochondria (products), and what causes this?
```
Acetoacetate
Acetone
3-hydroxybutyrate
-From high lipid intake and low carbohydrate intake (not enough oxaloacetate)
-starvation
-*diabetes
```
90
Ketonemia vs ketouria
Ketonemia- in blood
Ketouria- in urine
When the rate of formation of ketone bodies exceeds the rate of their use, their levels begin to rise in...
*seen in uncontrolled type 1 diabetes
91
What is a symptom of diabetic ketoacidosis?
Fruity odor of the breath (acetone)
92
Phospholipid composition
Composed of an alcohol that is attached by a phosphodiester bridge to either diacyglycerol or sphingosine
93
What are the two classes of phospholipids?
Glycerophospholipids/ phosphoglycerides
| Sphingophospholipid
94
All glycerophospholipids are derivatives of?
Phosphatidic acid
| Just a phosphate group as the head
95
Glycerophospholipids are formed from...?
Phosphatidic acid and an alcohol (from serine, ethanolamine or choline
96
What is cardiolipin and where is it found?
2 molecules of phosphatidic acid (PA) esterified through their phosphate groups to a glycerol.
In bacteria and eukaryotes
In eukaryotes, exclusive to inner mitochondrial membrane, seems to be required by the ETC
It is antigenic
97
What is a plasmalogen and where found?
When the fatty acid at carbon 1 of a glycerophospholipid is replaced by an unsaturated alkyl group attached via an ether (rather than ester) linkage to the glycerol backbone.
Abundant in nerve tissue
98
What is the composition of a platelet activating factor (PAF), and what does it do?
plasmalogen + an acetyl residue (rather than a fatty acid) at carbon 2 to the core glycerol molecule.
Triggers potent thrombotic and acute inflammatory events
99
What is an important constituent of the myelin nerve fibers?
Sphingomyelin
100
what is the backbone of sphingomyelin?
sphingosine (an amino alcohol, rather than glycerol)
101
A long chain fatty acid is attached to the amino group of sphingosine through an amide linkage, producing ___?
a ceramide
102
What is the alcohol group esterified to sphingosine to produce sphingomyelin?
phosphorycholine
103
Where are most phospholipids synthesized?
smooth ER
104
After the smooth ER, where do most phospholipids end up?
transported to the Golgi apparatus and then to membranes of organelles of the plasma membrane, or are secreted from the cell by exocytosis
105
What are the two most abundant phospholipids in eukaryotic cells?
Phosphatidylethanolamine
| Phosphatidylcholine
106
is sphingomyelin a major structural lipid in the membranes?
Yes
107
What enzyme hydrolyzes the phosphodiester bonds of phosphoglycerides?
phospholipases
| release molecules that can serve as 2nd messengers, ex IP3 and DAG
108
What enzymes degrades sphingomyelin, and where does it cut?
sphingomyelinase
It hydrolytic ally removes phosphorylcholine, leaving a ceramide
Ceramidase cleaves the fatty acid from the nitrogen, leaving sphingosine
109
What do glycolipids contain?
both carbohydrate and lipid components. Derivatives of ceramides in which a long chain fatty acid is attached to the amino alcohol sphingosine (glycosphingolipids)
110
Where are glycolipids primarily found?
nerve tissue
111
The carbohydrate portion of glycolipids are unique in that they are___?
antigenic
112
How do glycosphingolipids differ in structure than sphingomyelin?
They do not contain phosphate, and the polar head function is provided by a monosaccharide or oligosaccharide attached directly to the ceramide by an O-glycosidic bond (sugar)
113
What are the two main types of glycosphingolipids?
Neutral (glucose or galactose)
| Acidic
114
What are the simplest neutral glycosphingolipids?
cerebrosides
115
In acidic glycosphingolipids, what is providing the negative charge at physiological pH?
by N-acetylneuraminic acid (NANA) in gangliosides
| by Sulfate groups in sulfatides
116
Where and how does the synthesis of glycosphingolipids occur?
In the Golgi by
| sequential addition of glycosyl monomers transferred from UDP-sugar donors to the acceptor molecule
117
What are the enzymes involved in the synthesis of glycosphingolipids?
glycosyl transferases
118
"cerebroside" vs "globo"
```
cerebroside = 1 sugar
globo = 2+ sugars
```
119
Prostaglandins, and the related compounds thromboxanes and leukotrienes are collectively known as ___? Their origin is from...?
Eicosanoids
| origin from polyunsaturated fatty acids with 20 carbons
120
Main body responses from Eicosanoids?
inflammatory response
| hypersensitivity
121
What is the dietary precursor of prostaglandins and thromboxanes?
linoleic acid (w-6 fatty acid)
122
Where are eiconosides derived from?
```
Either arachidonic acid or
eicosapentaenoic acid (EPA)
```
123
What is the first step in the synthesis of prostaglandins?
The oxidative cyclization of free arachidonic acid to yield PGH2 by COX-1 (constitutive) and COX-2 (nonconstitutive)
124
What can inhibit prostaglandin synthesis?
cortisol
| aspirin
125
Leukotrienes (mediators of allergic response and inflammation) can be synthesized from AAs by what enzyme?
lipoxygenases
126
What is a cholesterol and what are two main functions?
a steroid alcohol
1. structural component of membranes, modulating fluidity
2. precursor of bile acids, steroid hormones and vitamin D
127
What organ plays a central role in cholesterol regulation?
Liver
128
Very little cholesterol results in what type of membrane?
less fluid
129
Where does cholesterol enter the liver from?
- Diet
- Cholesterol synthesized de novo by the liver
- extrahepatic tissues
130
What is cholesterol eliminated from the liver as?
-unmodified cholesterol in the bile
-converted to bile salts that are secreted into the intestinal lumen
secreted as VLDL
131
What parts of the body are the largest contributors of cholesterol synthesis?
Liver
Intestine
Adrenal cortex
Reproductive tissues
132
What are the three main phases of cholesterol synthesis?
Conversion of acetyl CoA to HMG-CoA
Conversion of HMG-CoA to squalene
Conversion of squalene to cholesterol
133
What is the key step in cholesterol synthesis? What is the enzyme involved? and what is the rate limiting product?
Conversion of HMG-CoA to squalene (step 2)
HMG-CoA reductase
Mevalonate
134
What is the relationship between cholesterol and HMG-CoA reductase?
cholesterol inhibits the reductase and catalyzes its breakdown
135
What is unique about the rings structure of cholesterol and how it is metabolized in humans?
It cannot be metabolized to CO2 and water in humans
136
How is the intact sterol nucleus, in cholesterol, eliminated from the body?
It is converted to bile acids and bile salts in the liver
137
Where is bile stored?
gall bladder
138
What is the path of cholesterol to bile salt?
cholesterol --> bile acid --> bile salt
139
cholic acid is an example of what?
a bile acid
140
What happens to bile acids before they leave the liver, and what does it do to their chemical property?
they are conjugated to a molecule of either glycine or taurine. This makes them more soluble
141
What does bile contain?
bile salts, cholesterol, phospholipids, bile pigment (bilirubin and biliverdin)
142
Where is yellow-green bile produced and stored?
produced in hepatocytes
| stored in gall bladder
143
Bile aids in absorption? Y/N
Yes
144
4 examples of lipoprotiens
Chylomicrons
VLDL
LDL
HDL
145
What do LDLs do?
deposit cholesterol in the arteries
146
What do HDLs do?
transport cholesterol to the liver for conversion to bile acids and for disposal
147
What is the precursor for all classes of steroid hormones?
cholesterol
148
How are cholesterol hormones transported to their target organs?
via the blood (they must be complexed with a plasma protein because of their hydrophobicity)
149
T/F: Chylomicrons deliver endogenous triacylglycerol to peripheral tissues.
False; they deliver EXOGENOUS (made outside of the body)
150
Dihydroxyacetone phosphate can be converted to glycerol phosphate in the liver by the enzyme___?
Glycerol phosphate dehydrogenase
151
Important vitamin for FAD?
B2; riboflavin
152
```
A ganglioside may contain all of the following except;
A: a ceramide structure
B: glucose or galactos
C: phosphate
D: one or more sialic acid
E: sphingosine
```
C: phosphate
153
What is needed to derive thromboxane?
linoleic acid
