Lipid, Cholesterol and Bile Acid Synthesis Flashcards
Contains 1/2 Week 6 Material (155 cards)
1
Q
What is the most fundamental structure of lipids?
A
Fatty Acids
2
Q
Which kinds of fatty acids have double bonds?
A
Unsaturated
3
Q
What is the nomenclature for unsaturated fatty acids?
A
Total# of carbons : (# of double bonds) △ ^ (# carbon where double bond starts INCLUDING C from carboxyl carbon)
If the fatty acid is poly-unsaturated, we add commas to indicate the starting point of additional double bonds.
4
Q
What is an omega carbon?
A
The last carbon in the chain
5
Q
How can we use omega carbons to describe fatty acid nomenclature?
A
Omega________
_____ will be number of carbons from omega carbon that starts the double bond closest to the terminal carbon
Include omega carbon when countin
6
Q
What are the three essential fatty acids?
A
- Linoleic Acid (Omega-6)
- Alpha- linoleic acid (Omega 3)
- Arachidonic Acid (Omega 6)
7
Q
What happens if you lack the three essential fatty acids?
A
- Skin and kidney damage
- Cataracts
- Increased membrane permeability of water
8
Q
All double bonds in naturally occurring polyunsaturated fatty acids are in _____ configuration.
A
cis
9
Q
Arachidonic Acid is a major precursor of _______.
What are they?
How many carbons?
A
Eicosanoids
Prostaglandins, thromboxane, leukotrienes are 20 carbon fatty acids and powerful physiological regulators
10
Q
How does arachidonic acid play a role in our bodies?
A
Arachidonic acid is ingested from the diet and combines with a phospholipid to enter the cell membrane of a tissue cell.
Phospholipase A2 will cleave the ester bond in the second fatty acyl chain to release AA from the cell membrane into the cytosol of the cell. AA is now able to become
- Epoxides
- Leukotrines
- Thrombonxane
- Prostaglandins
which are all 20 carbon fatty acids called Eicosanoids
11
Q
Eicosanoids come from _________. Examples include __________ and their function is to _______.
A
Arachidonic Acid
- Epoxides
- Leukotrines
- Thrombonxane
- Prostaglandins
Regulate BP
Muscle Contraction
Bronchodilation and constriction
Water/Sodium Excretion
Inflammatory Response
12
Q
Thromboxine is responsible for stopping ______.
A
Bleeding
13
Q
Prostaglandins and Thromboxane have precursors of ________ and ________.
A
Arachidonic Acid and Linoeic Acid
(Eicosanoids have precursors of the ^^)
14
Q
Essential fatty acids come from ______.
A
Our diet
15
Q
Where can you find trans-fatty acids?
A
Food products, especially processed ones and baked goods!
16
Q
Trans-fats occur naturally.
True or false?
A
FALSE
It is made by food corporation.
17
Q
How much trans-fat does an Oreo have?
A
2.5g
18
Q
How are trans-fatty acids made?
A
Transfer acids are formed during hydrogenation a process that solidifies liquid vegetable oil by adding hydrogen atoms to the double bonds of unsaturated fatty acids.
19
Q
What is hydrogenation?
A
The addition of hydrogen. In the case of fatty acids hydrogenation is the process that takes cis-unsaturated fatty acids and makes them trans- fats
20
Q
Linoieic Acid when hydrogenated becomes _________ which has _____ double-bond.
A
Elaidic Acid
Trans-double bond
21
Q
What types of unsaturated fatty acids make membrane packing loose ?
What types of unsaturated fatty acids make membrane packing tight?
A
Cis-fatty acids
Trans-fatty acids
22
Q
What occurs in cis-unsaturated fatty acid stacking that causes it to pack _____ ?
A
loosely
the cis-configuration of the double bond causes a 120 degree kink in the chain creating spaces between chains that creates the membrane fluidity.
23
Q
Why is it important for our membrane to be able to pack loosely?
A
Membrane fluidity allows for entrance of molecules into the cell (aka plasma membrane)
24
Q
Trans fatty acids increase __________
Trans fatty acids decrease ___________
They can lead to ______
A
LDL
Triacylglycerol
Platelet Aggregation
HDL
Growth retardation in newborns
25
Fish oil is rich in _______ fatty acids which can decrease ___________.
Cis Omega-3 polyunsaturated fatty acids
Cardiovascular mortality
26
What other food item can contain lots of Omega-3?
Eggs
(Probably modified tho)
27
What is the structure of a triacylglycerol?
Carbon with 1 Hydrogen + 3 Variable hydrocarbon chains with a variable number of carbons and double bonds
28
Where are triacylglycerols stored?
Adipose Tissue
29
What acylglcerols are abundant in mammal cell membranes?
Phosphosacylglycerol
Sphingolipids
Cholesterol
30
Phosphosacylglycerols is also called ___________.
Describe the structure
Glycerophospholipids
Glycerol Backbone
C1- Fatty Acid
C2- Fatty Acid
C3-Phosphate moiety + Head group
31
Phosphatic acid is ________ with _________ on the C3 of the ______.
Phosphoacylglycerol with one phosphate acid on the C3 of glycerol
32
If a choline moeity group is attached to the _______ on the C3 of acylglycerol, what is the compound called
Phosphatidylcholine
33
At ph=7, the amine group of Phosphatidylcholine is _________, the phosphate is _______.
Net charge is :
What is another name?
Postitive
Negative
0
Lecithin
34
The ________ attached to the C3 carbon of glycerol is ________ and will face the _______ of a compound.
Phosphate + head group
Polar
Outside (facing water)
35
What charges will exist on the SURFACE of cell membrane and why?
Neutral or Negative
Think about Phosphatidylcholine and Phosphatidic Acid
Phosphates are negatively charged = -
Phosphate + The addition of a polar head group = Neutral
36
Phosphatidylinositol 4,5 - bisphosphate (PIP2) carries what charge?
Why is it important?
Negative or no charge
It is a degradation product that serves as important signaling molecules.
Phosphoacylglycerol
37
If a lipid only has one fatty acid chain, what is it called?
Lysolecithin or Lyso-PC
38
Lyso means ________.
One fatty acid chain on the glycerol molecule
39
Phosphoacylglycerols are important for _________
1. Cell membrane Structure
2. Signal Transduction
3. Metabolic Pathway
4. Membrane fluidity and lateral organization
5. Cell membrane function
6. Lung Surfectants
40
What makes lung surfectants?
Phosphoacylglycerols
41
All sphingolipids are derived from ________.
What is the backbone of sphingolipids?
Ceramide
An 18-carbon structure made of sphingosine + fatty acyl chain
Ceramide is the compound when the amino group of sphingosine is linked to an acyl chain
42
Sphingosine is a major/minor part of _______.
What is on C1 ,C2 and C3 of the ceramide
Major part of ceramide- it IS the backbone
C1- OH or some variable group
C2- Amino group with hydrocarbon chain
C3- OH with long hydrocarbon chain
43
Sphingomyelins can be split into two groups. What are they?
Sphingomyelin and Sphingoglycolipid
44
All sphingolipids come from _________.
The first carbon of ceramide is attached to a _________.
What happens if that group is replaced with
1. Phosphorylcholine
2.Galactose
3.Oligosaccharide
Ceramide
-OH
1. Sphingomyelin
2. Galactocerebroside
3. Ganglioside
45
How are sphingomyelins made?
Sphingomyelin is a type of sphingo___
Addition of phosphorylcholine to C1 of ceramide
Sphingolipid
46
What are the similarities between Sphingolipids and Phosphoacylglycerols?
1. Polar moiety on first Carbon
2. Second Carbon has long hydrocarbon chain
3. Long hydrocarbon chain on 3rd carbon.
ASKKKK
47
In phosphoacylglycerols, fatty acids are attached to glycerol via _____ linkages, whereas in sphingolipids, a fatty acid is attached to sphingosine via an ____ linkage
ester
amide
48
Sphingolipids are key components of _______ and regulators in ________.
What are two key sphingolipid metabolites ?
Cell membranes;particulary nerve cell membrane
regulators in cell death/survival, toxin binding, cell-cell recognition
S1P
Ceraminde
49
What is S1P?
SphingoSINE 1- Phosphate that develops from sphingolipid degradation
Stimulates cell proliferation and survival, regulates cell motility and cytoskeletal reorganization
50
What is ceramide?
Apoptosis regulator
When sphingolipid is degrades, they regenerate ceramide.
51
Cholesterol is non-soluble in water and therefore _____. It's signature feature is a ________.
Can humans degrade this structure?
non-polar
Tetracycline Ring
NO
52
Free cholesterol can be converted to ________.
Cholesterol esters
53
Cholesterol is a major component of cell membrane and is embedded into the membrane.
True or False
FALSE
Located INSIDE cell as part of oily droplets or located in blood lipoprotein particles
54
Cholesterol can insert itself into the _________ formed by ________.
Bilayer
Sphingolipids and phosphoacylglycerols
55
Can cholesteryl esters enter the cell membrane?
NO
They aggregate with triacylglycerols to transfer themselves into the cell membrane.
56
What is the component in cell membranes that keeps it stable?
Cholesterol
57
What makes up the hydrophilic head of phosphoacyl glycerols?
Phosphate + Moiety on Carbon 3
58
Integral proteins insert themselves ___________ the membrane while peripheral proteins ________ the membrane.
All the way through
Half-way
59
Most dietary lipids are _______.
Triacylglycerols
60
Dietary TGs are digested by _________ produced by glands in the _________ and _______.
When they reach the _____, they can be digested by _______.
Both of these substances have pH of _______.
What do TG's break down into?
Lingual Lipase, Tongue and Soft Palate
Stomach, Gastric Lipase
4-5
Fatty acids and DIacylglycerol
61
Lingual lipase and gastric lipase prefer to hydrolyze what kind of triacylglycerols?
Why is this important for BABIES?
short-chain and medium-chain ( less than 12 carbons on acyl chains)
SCTGs and MFTGs are abundant in milk
62
Major part of digestion occurs in the _________.
What does digestion of lipids (TGs) require along with ______and _______ ?
Lumen of Small Intestine
Lingual and Gastric
1. Bile Salts
2. Pancreatic Lipase
3. Co-Lipase
4. Bicarbonate (HCO3-)
**These are after breakdown by lingual and gastric lipase**
63
Bile acid is produced from _________ in the _______ and thus has a _________.
Cholesterol in the liver
Tetracycline Ring
64
Bile can exist at two different forms. What are they and when do they exists?
Bile Acid which is the protonated form COOH
Bile Salt which is the anionic deprotonated form COO-
65
Which form of bile exhibits detergent properties and why?
Anionic Form (COO-) BILE SALT
66
Which bile form is most abundant at neutral body ph?
Anionic Bile Salt
67
Digestion uses bile _____.
SALT
Anionic
Deprotonated COO-
68
Emulsion particles are ______, about _____ micrometers.
Mixed micelles are _____, about ______micrometers
Large , 1-20 micrometers
Small, 4-7 micrometers
69
Cholesterol will be present on the _______ of the emulsion droplet while cholesterol esters will be present _______.
Outside
Inside
70
TAGs will be present __________ emulsion droplet
inside
71
Monoacylglycerols will be present ________ emulsion droplet
Outside
72
When bile enters the small intestine, bile salts break down ___________into_________ through a process called emulsification.
When bile enters the small intestine, bile salts break down large fat globules into smaller micelles through a process called emulsification.
73
Pancreatic lipase is attracted and anchored to the ________ by _______.
Emulsion particles by CO-lipase
74
Pancreatic lipase cleaves the _______ bond of the TAG to remove a ________ creating a ______. This process occurs once more until ___________ is made.
Ester bond
Fatty acid to create a diacylglycerol
This process continues to until a 2-monoacylglycerol is made.
75
The final product after pancreatic lipase hydrolyzes the ester bonds of triacylglycerol is _________.
2- Monoglycerol
76
Bile salts create __________ that are recognized by _______ and broken down by _________.
emulsion particles that are recognized by co-lipases and are broken down by lipases.
77
What does HCO3- do?
Bicarbonate reduces the pH of the small intestine and increases anionic species. This promotes lipid digestion and absorption by increasing enzyme activity.
78
What are the final degradation products of lipid metabolism and where are they located?
Fatty Acid and 2-Monoacylglycerol in lumen of small intestine.
79
How do the products of dietary TG's get to the rest of the body from the small intestine lumen?
1. Dietary TGs have been hydrolyzed to 2-monoacylglycerol and fatty acids
2. Mixed micelles formed by many lipid soluble materials including FA, 2-MG and Bile salts are taken up by intestinal epithelium via endocytosis.
3. TG's are re-synthesized in intestinal epithelial cells and combine with other lipid-soluble materials and apo-proteins to form chylomicrons.
4. Chylomicrons are lipoprotein molecules released into lymph and eventually to blood for other organs to take up.
80
What are cholymicrons?
The name for the lipoprotein resynthesized TAGs that have been transported from the intestinal epithelial cells to lymph for transport to the blood.
81
Lipid Malabsorption can be caused by __________
deficiency in pancreatic lipase or bile acid
Steatorrhea or lipid accumulation in feces could occur
LOSS of important fuels, weight loss and vitamin loss, fatty acid deficiency
82
What are the 4 fat-soluble vitamins?
ADEK
83
What is the major organ that synthesizes fatty acids?
Liver
84
What is the most abundant fatty acid in the body?
Palmitate
85
Describe the general flow from glucose to fatty acids.
Glucose goes through glycolysis and pyruvate dehydrogenase to made Aceytl CoA.
Aceytl CoA will go into fatty acid synthesis to generate a LCFA, such as palmitate, which can be made to Fatty Acid CoA.
This Fatty Acid CoA will combine with glycerol 3 phosphate to make a TAG.
TAG will combine with other lipids to make VLFCA and enter the blood.
86
Starting material for fatty acids is ______ which contains ______ carbons.
Acetyl-CoA
2
87
Palmitate has _____carbons.
16
88
Fatty acid synthesis from carbohydrates starts with the _____________.
Conversion of glucose to mitochondrial Acetyl-CoA.
In order for Acetyl-CoA to be produced from pyruvate. The pyruvate dehydrogenase enzyme is required.
89
_________ is present only in the _______ and is required to catalyze the conversion of ____________ into Acetyl-CoA.
The reaction as a _________ delta G and is __________.
Pyruvate dehydrogenase is present only in the mitochondria and is required to catalyze the conversion of pyruvate to acetyl-CoA.
Negative delta G and is irreversible
90
Pyruvate dehydrogenation in the mitochondria is reversible. True or False.
FALSE
91
Acetyl CoA is very ______ and has ________ charges at neutral pH.
It cannot pass through the ___________.
What happens next?
large, 4 negative
mitochondrial membrane
Pyruvate carboxylase converts pyruvate to oxaloacetate. This combines with Acetyl CoA to make citrate which is transported to the cytosol via tricarboxylate translocation.
Citrate will break down into OAA and AcetylCoA
92
Pyruvate has been dehydrogenated in the ______________ by ________ to ____________.
____________ cannot exit the ___________membrane
_________ will turn ________ into __________. _______ will combine with _________ to make _________.
___________ will leave the __________ via ___________ and break off into _______.
mitochondria, pyruvate dehydrogenase to Acetyl CoA
Acetyl CoA cannot exit the mitochondrial membrane
Pyruvate carboxylase will turn Pyruvate into oxaloacetate. OAA will combine with AcetylCoA to make Citrate
Citrate will leave the mitochondrial membrane via tricarboxylate translocase to enter the cytosol and break off into the OAA and AcetylCoA
93
What two compounds are required to synthesize long-chain fatty acids?
NADPH and Acetyl CoA
94
What generates NADPH necessary for the synthesis of long-chain fatty acids?
The Malic Enzyme Pathway and The Pentose-Phosphate Pathway
95
When NADPH is high, what rate-limiting enzyme of the pentose phosphate pathway is regulated?
Glucose 6 Phosphate Dehydrogenase
96
What is the rate-limiting enzyme in the pentose phosphate pathway?
Glucose 6-Phosphate dehydrogenase
which converts Glucose 6-Phosphate to 6-Phosphoglucono-lactone
NADP+ is converted to NADPH
97
NADPH is mainly for ___________
NADH is mainly for _________.
Reductive biosynthesis such as synthesis of cholesterol and fatty acids
ATP generation
98
Remember in fatty acid transport, __________ inhibits the __________ that is required to shuttle fatty acids across the mitochondrial membrane.
Why is this important?
Malonyl CoA, Carnitine
Fatty acid synthesis and beta-oxidation both occur in the mitochondria! When one is occuring we don't want the other to happen! So the production of Malonyl CoA inhibits fatty acids from entering the mitochondria for breakdown when synthesis is needed instead.
99
What is the rate-limiting step in fatty acid synthesis?
Where does it occur?
Carboxylation of Acetyl-CoA to form Malonyl CoA by Acetyl CoA Carboxylase
100
What is the most important enzyme in fatty acid synthesis ?
What does it do ?
Acetyl CoA Carboxylase
Add a CO2 to Acetyl CoA to create Malonyl CoA
101
What key component is required for the carboxylation of Acetyl CoA to Malonyl CoA via ________ ?
Describe the interaction
Acetyl CoA Carboxylase
Biotin is required!
The lysine residue of Acetyl CoA Carboxylase will covalently link to the carboxyl group of biotin to make Enz-biotin complex
The nitrogen on the cyclic portion of biotin becomes very reactive and will bind a CO2 to make an enzyme intermediate that is very unstable that has a HIGH tendency to loose the CO2 to a substrate such as ACoA.
102
Why is biotin key?
Biotin incorporates with Acetyl CoA Carboxylase to make Malonyl CoA by serving as a CO2 carrier for Acetyl CoA.
103
The fatty acid synthase complex contains monomers made of __________ in the polypeptide chain.
These monomers are arranged as a ________.
8 components
7 enzymes + Acyl Carrier Protein
HOMODIMER. There are 2 monomers that are exactly the same.
104
Describe the monomers of the fatty acid synthase complex and how they form a homodimer.
Monomer 1 and 2
Cysteine with SH --------- SH- PPT
7 enzymes
Phosphopanthertheine with SH ---------SH Cysteine
The SH of the Cysteine residue on Monomor 1 and the SH of the Phosphopantherteine residue on Monomer 2 will align and form bonds.
105
Where are the elongation centers in the fatty acid synthase complex?
Where the Monomer residues align in the homodimer.
At the SH-SH bonds!
106
Why is the SH group on phosphopantetheine important ?
PPT is attached to the Acyl Carrier Protein. PPT is covalently linked to a serine residue to the acyl carrier protein segment of the enzyme.
The SH group on phosphopantethiene covalently binds with malonyl-CoA to form a thioester during fatty acid synthesis.
107
The SH group on phosphopantethiene, which is associated with a ______ residue on ________, covalently binds with ________ to form a _______ during fatty acid synthesis.
The SH group on phosphopantethiene , which is associated with a serine residue on ACP, covalently binds with malonyl-CoA to form a thioester during fatty acid synthesis.
108
The cysteine residue with ____ is associated with ______ on the opposite end from __________.
Ketoacyl synthethase
SH
Phosphopanethine +ACP complex
109
Describes the steps of fatty acid synthesis now that we have formed the fatty acid synthase complex
1. Acetyl CoA will bind to the SH on the PPT+ACP complex. It can shift over to the Cystein-Ketoacyl synthetase complex as well.
2. Malonyl CoA formed from Acetyl CoA by acetyl CoA carboxylase will attach the SH group on the PPT+ACP complex (it is empty now that the Acetyl CoA group has shifted to the other elongation site)
3. Acetyl Co-A and Malonyl Co-A combine and undergo a decarboxylation reaction.
4. NADPH is oxidized twice to complete an elongation cycle which pushes the reduction of the compound until the wanted fatty acid is formed.
110
How many carbons is the molecule that yields after 1 round of elongation by fatty acid synthase?
1. Acetyl-CoA add 2 Carbons
2. Malonyl Co-A adds 3 Carbons
3. The decarboxylation when Acetyl CoA and Malonyl CoA combine results in a loss of one Carbon Dioxide
Final : 4 Carbon molecule
111
How much NAPH is used in one cycle of fatty acid elongation?
2!
NADPH is OXIDIzed and serve as a reducing agen
2. Carbonyl to hydroxyl
4. Reduce double bond to single bond
112
In the first chain elongation cycle
Malonyl CoA provides ______ carbon units.
NADPH serves as ______.
2 carbon units
Reducing Agent (NADPH itself gets oxidized)
113
What happens in the second elongation cycle?
Exactly same thing as first!
114
How do we release fatty acid from the fatty acid synthase complex?
Thioesterase cleaves the thioester bond between the fatty acid and the synthetase complex.
115
Can the body synthesize fatty acids with a chain length shorter than 16Cs?
Yes!
Thioesterase can cleave the fatty acid chain at different points during the synthesis cycle but prefers to have 16 carbonds as palmitate.
116
Can we synthesize fatty acyl chains LONGER than 16 carbons?
Yes!
Convert palmitate to Palmitoyl CoA.
Use Malonyl CoA to insert 2 carbons into the chain and use NADPH
117
How does the body synthesize fatty acids containing double bonds?
There system of 3 proteins embedded in the Endoplasmic Reticular Membrane that adds electrons to single carbon-carbon bonds to make it a double carbon-carbon bond.
118
We know that the ER membrane has a system that can turn saturated fatty acids into a monounsaturated fatty acids by adding double bonds via ___________. How can we generate polyunsaturated fatty acids?
fatty acyl CoA desaturase
different kinds of desaturases
119
Humans lack enzymes to introduce double bonds between ________ and ________.
What can add double bonds at these points?
Carbon 10 and the terminal carbon
PLANTS
120
Why are essential fatty acids important?
Linoleic, Alpha-linoleic and Arachidonic acid are all fatty acids which have double bonds past the 10 carbon.
Humans cannot synthesize double bonds between C10 and the terminal carbon so we need to eat these fatty acids instead.
121
Free fatty acids are safe for our cells. True or False?
False!
We need to covert Free Fatty Acid to Fatty Acid CoA. This also makes the compound high energy?
122
Free fatty acids get converted to _________ and react with ________ to form __________.
These combine with other lipids and proteins to form _________.
Fatty acyl CoA and react with Glycerol-3-P to form triacyl glycerols.
These combine with other lipids and proteins to form VLDLs.
123
Triclosan is found in ________.
Why is it important?
Toothpaste, Laundry Soap, Cosmetics, Mouthwash, Antimicrobial Soap
Kills bacteria and yeast by inhibiting an Acyl Carrier Protein Reductase which is necessary for fatty acid synthesis in germs.
124
Triclosan can cause _________ resistance.
Antibacterial
125
What is a triclosan alternative?
Stannous Flouride
126
Acetyl CoA carboxylase is active in the ________ state catalyzed by ___________.
Therefore, fatty acid synthesis is active in the _______.
dephosphorylated, insulin-stimulated phosphatase
fed state
127
Low energy levels cause ________ to be rendered inactive via _________ by _______.
Acetyl CoA Decarboxylase to be rendered inactive via phosphorylation by AMP-activated protein kinase.
128
When insulin is high, _________ is active which allows __________ of __________.
Phosphatase, phosphorylation of Acetyl CoA Carboxylase
129
Which enzymes are induced after a high-carb diet?
1. Pyruvate Dehydrogenase
2. Acetyl CoA Carboxylase
3. Fatty Acid Synthase
4. Citrate Lyase
5. G-6-P Dehydrogenase (Pentose Phosphate Path)
130
Cholesterol synthesis occurs in the _________ particularly on the ___________ of the __________.
Which organs?
cytosol, cytoplasmic face of the Endoplasmic Reticulum
Liver and Intestinal Cells
131
What is the rate limiting step in cholesterol synthesis?
What is the rate limiting enzyme in cholesterol synthesis?
1. HMG-CoA to mevalonate is the rate limiting STEP
2. Its enzyme, HMG-CoA reductase is the rate limiting enzyme
132
HMG-CoA reductase is associated with _______.
Cholesterol synthesis
133
The _______ domain of HMG-CoA faces the _________ while the rest of the molecule is embedded in _________.
N-terminal , cytoplasm
Endoplasmic Reticulum Membrane
134
What is the first step of cholesterol synthesis?
Acetyl CoA is converted to AcAcCoA
AcAcCoa is converted to HMG Co-A via HMG Co-A synthase
HMG Co-A is converted to Mevalonate via HMG Co-A reductase. NADPH is also oxidized to NADP+
135
What are the products of the first step of cholesterol synthesis?
1. NADP+
2. Mevalonate
136
HMG Co-A synthase is found in the _________.
ER membrane with N-terminus facing cytoplasm
137
What is the second step of cholesterol synthesis?
Formation of activated isoprene units
Condensation of SIX 5-carbon isoprenes from the 30-square squalene
Isoprenes are made from mevalonate
(Mevalonate to 30 square squalene)
138
What is stage three of cholesterol synthesis?
30 carbon squalene to cholesterol involving another oxidation of NADPH.
139
What are the generic steps of cholesterol synthesis?
1. Acetyl CoA to Mevalonate via HMG CoA reductase and NADPH oxidation
2. Mevalonate to 30-carbon squalene
3. Conversion of squalene to cholesterol.
140
HMG Co-A Reductase Regulation
How is transcriptional control done?
There are two key proteins
1. SREBPs - Sterol Regulatory Element Binding Proteins
2. SCAP - SREBP cleavage activating protein
When cholesterol is high, these proteins will transfer to the golgi membrane. The DNA binding domain of SREBP will be cleaved after exposure to two proteases in golgi. This promotes transcription of HMG CoA reductase.
141
When cholesterol content in cell is high, how is transcription of HMG CoA affected?
HMG CoA reductase will be degraded
142
How does insulin affect cholesterol synthesis?
Insulin will remove a phosphate group from HMG-CoA reductase to render it inactive.
Remember if we have insulin, we have been FED!
143
Where is cholesterol synthesized?
Liver
144
Bile Salt synthesis occurs only in the ______.
Liver
145
What is the rate limiting enzyme of bile salt synthesis from cholesterol?
7alpha- hydroxylase
145
What are the two bile acids made in the liver?
Chenodeoxycholic Acid
Cholic Acid
146
Bile acid can conjugate _______ and ______ to reduce the ________. This makes them ________.
Taurine and Glycine
pKA
better emulsifying agents
147
Conjugated bile acids are important for __________. They are stored in the ______ and secreted into the _______ to aid in _________.
Serving as good emulsifying agents due to their low pkA
They are stored in the gallbladder and secreted into the intesting to aid in digestion
148
Bacteria in the _________ does what to bile salts?
Large Intestine
Deconjugate
Dehydroxylate
As a result, bile acid may become so non-polar that it cannot enter back to the liver. Instead they are excreted by the body.
149
What is a common secondary bile salt?
What is a secondary bile salt?
These are bile salts that bacteria have deconjugated or dehydroxylated rendering them too non-polar to enter the liver.
Lithocholic Acid
150
Conjugated bile acids are ________.
Primary Bile Acids
151
Why is it important to have secondary bile acids?
They help remove cholesterol from our bodies!
152
Lipid degradation is particularly important for ___________ which are derived from condensation of ________ and ______.
Sphingolipids
Palmitoyl CoA and Serine
153
Niemann-Pick Disease
What is the key enzyme?
Patients are unable to digest sphingolipids causing a buildup of fats.
Sphingomyelinase is the key enzyme.
154
What diseases can be caused by the lack of ability to digest sphingolipids?
1. Tay-Sachs
2. Gauchers
3. Neimann Pick
