Chapter 29: Cholesterol Metabolism Flashcards
1
Q
Circulating levels of cholesterol are a balance between
A
- What is consumed in diet
- What is made in the body
2
Q
Consumption of less cholesterol causes the body to
A
- Produce more
- Makes it difficult to reduce cholesterol by dietary means alone
3
Q
Cholesterol is ubiquitous in
A
- Animal cells
4
Q
Cholesterol solubility
A
- Considered amphipathic
- Weakly soluble in water
5
Q
Cholesterol is linked with
A
- Cardiovascular disease
6
Q
Cholesterol is often found stored in cell or
A
- Transported around the body
7
Q
Cholesterol esters
A
- Hydropobic
- Much less polar fatty acids
- Transport cholesterol
8
Q
The more hydrophobic cholesterol esters are transported in
A
- The core of a lipoprotein
- FA is attached
9
Q
Cholesterol is transported in
A
- The outer phospholipid coat of lipoproteins
- (Phospholipid monolayer on the outside)
10
Q
All carbon atoms of the cholesterol molecule are derived from
A
- Acetate
11
Q
Rings of the cholesterol molecule are attached to a
A
- Branched hydrocarbon chain
12
Q
Carbons of the cholesterol molecule come from acetate via
A
- Acetyl-SCoA
13
Q
Cholesterol molecule structure is characterized as
A
- Weakly amphipathic
- Hydrophobic
14
Q
Cholesterol esters are very
A
- Hydrophobic
15
Q
Cholesterol has the following functions
A
- Precursors of bile acids
- Membrane stabilization
- Precursor of steroid hormones
- Cholecalciferol (vitamin D3)
- NOT an energy substrate
16
Q
Cholesterol is not broken down, but
A
- Converted to bile acids and secreted from the body
- NOT an energy substrate (no ATP production from breakdown)
17
Q
Cholesterol derivatives are precursors to active
A
- Vitamin D
- Means we can make vitamin D in the body
18
Q
We can make vitamin D in the body by
A
- Exposing the skin to sunlight
19
Q
Enzymes for cholesterol biopsyntehsis are located in
A
- Cytosol
- ER
20
Q
Enzymes for cholesterol biosyntehsis
A
- Produced in most tissues
- NADPH-dependent (NADPH from the PPP)
21
Q
PAtheay of cholesterol biosyntehsis overall
A
- Acetoacetyl-SCoA formation in cytoplasm
- HMG-SCoA production (also found in ketogenesis)
- Production of mevalonic acid (committed step)
22
Q
Acetoacetyl-SCoA formation in cytoplasm
A
- Acetyl-SCoA must exit mitochondris
- Two acetyl-SCoA molecules condensue to form acetoacetyl-SCoA
- Acetyl-SCoA transferase
23
Q
HMG-SCoA production (also found in ketogenesis) is catalyzed by
A
- Cytosolic HMG-SCoA synthase
24
Q
Production of mevalonic acid (committed step) is catalyzed by
A
- HMG-SCoA reductase
25
First intermediate that is unique to the pathway of cholesterol biosynthesis
- Mevalonic acid
26
Condensation of a third molecules of acetyl-SCoA with acetoaetyl-SCoA to form
-
27
The rate limiting step of cholesterol biosynthesis is catalyzed by
- HMG-CoA reductase
- Irreversible
- Far from equilibrium
28
HMG-SCoA is reduced to
- Mevalonic acid in an irreversible reaction
- NADPH requirement
- Key step in cholesterol biosynthesis
29
Insulin _____ HMG-SCoA activity
- Insulin promotes its activity
30
HMG-SCoA is _____ when active
- Dephosphoprylated
| - Connected with biosynthesis in the presence of insulin
31
Mevalonic acid is phosphorylated and decarboxylated to
- Isopentenyl pyrophosphate
32
Isopentenyl pyrophosphate is formed by
- Phosphorylation and decarboxylation of mevalonic acid
33
Isopentenyl pyrophopciate is a
- 5C isporene unit
34
Two 5C isoprene units condense to form
- 10C geranyl pyrophosphate
35
A third 5c isoprene is added, forming
- 15C unit
| - Farnesyl pyrophosphate
36
Finally, 2 farnesyl groups condense to form
- 30C linear compound
- Squalene
- Reaction is catalyzed by squalene synthase
37
Squalene is converted to
- Cholesterol
| - Squalene > Lanosterol > cholesterol
38
Squalene is transformed by
- Series of ring closure steps
- Oxidized to the sterol (Lanosterol)
- Which is converted to cholesterol in 19 steps
39
End product inhibition of HMG CoA reductase by
- Endogenously produced and by dietary cholesterol
| - End product feeds back and inhibits this enzyme
40
Proteasome degradation of the enzyme is stimulated by
- Cholesterol
| - (Rate of HMG CoA reductase degradation)
41
Reversible covalent phosphorylation of HMG CoA reductase
- Inhibition by phosphorylation by AMP-activated protein kinase
- Favored by glucagon and epinephrine
- Active in the dephosphorylated state
42
Regulation of cholesterol biosynthesis (HMG-SCoA reductase) involves
- Dietary cholesterol
- Bile acids
- Hormones
- Drugs
43
Regulation of cholesterol biosynthesis by HMG-SCoA reductase is inhibited/activated by
- Inhibited by phosphorylation
| - Activated by dephosphorylation
44
Dietary cholesterol returning to the liver reduces the activity of
- HMG-SCoA reductase enzyme
45
HMG-SCoA reductase is a massive target for
- Statins
46
The statins
- Resemble HMG-CoA
| - Competitive inhibitors of HMG-CoA reductase
47
In the hepatocyte, cholesterol is converted to
- Bile acids
48
Bile acids are polar derivatives that represent
- The sole end product of cholesterol metabolism
49
Two phases of the synthesis of bile acids
- Hydroxylation
| - Conjugation of cholesterol with amino acids
50
Overall goal of bile acid synthesis
- To increase the solubility of bile acids so they can be secreted out of the body
- Done by adding hydroxyl groups and attaching amino acids (making bile acid conjugates)
51
Bile acids are _____ water-soluble than cholesterol
- More water-soluble
| - Something becomes more polar, it becomes more water-soluble
52
Attaching amino acids during bile acid synthesis makes
- Bile acid conjugates
| - Conjugates are much more water soluble than original biel acid
53
Choelsterol exretion requires the formation of
- Primary bile acids
| - Ch
54
Conjugation occurs in
- The liver
| - Prior to secretion into the biliary canaliculus
55
Taurine conjugate
- Taurocholic acid
56
Glycine conjugate
-
57
Bacterial metabolism
- Process by which secondary bile acids are formed
| - Formed from primary bile acids
58
Essentially, bacterial metabolism is considered
- Dehydroxylation
59
Bile acids are the only significant
- Excretion product of cholesterol
| - Aid cholesterol solubility
60
Bile acid sequestrants
- Colestipol (Colestid)
| - Cholestyramine (Questran)
61
Bile acid sequestrants are used in the treatment of
- Hypercholesterolemia
62
Anionic resin-bile acid conjugates
- Excreted in the feces
| - Serum cholesterol levels are reduced since existing cholesterol is diverted into the replacement of these bile acids
63
Bile acid sequestrants cause liver cells to express
- More LDL receptor proteins
| - Further reduces circulating LDL-cholesterol levels
64
Generally, bile acid sequestrant drugs are extremely
-
65
Substances secreted into the bile (enterohepatic circulation of bile acids) are first stored in
- Gall bladder
| - Then released into the intestine
66
After being released into the intestine, the substances secreted into the bile are then
- Reabsorbed into the intestine
| - Then returned to the liver via the portal circulation
67
Colestipol is a bile acid sequestrant effective in
- Reducing circulating cholesterol levels
68
Bile acid sequestrants have a complimentary charge that allows
- Binding to bile acids
| - Prevention of recycling of bile acid(avoiding return to the liver)
69
With bile acid sequestrants, the liver directs cholesterol that is not recycled to
- Bile acid formation
| - Much better option for cardiovascular risk
