Lipid Metabolism I Flashcards
1
Q
Fatty acids are stored as
A
Triacylglycerols (TAGS) in adipose Tissue
2
Q
Triacylgycerols (TAG) are highly concentrated stores of metabolic energy because they are
A
reduced and anhydrous
3
Q
TAGs are uncharged _____ of fatty acids with glycerol
A
esters
4
Q
TAGs are the building blocks for
A
phospholipids and glycolipids
5
Q
TAGs present in diet must be
A
broken down to fatty acids for absorption
6
Q
_____ fuel long migration flights of birds, such as the American golden plover
A
Triacyglycerols
7
Q
Intestinal enzymes called ______, secreted by the _____, degrade triaglycerols to free fatty acids and monoacylglycerol
A
Lipases, pancreas
8
Q
____ and _____ present in tongue and stomach, respectively, digest short and medium chain Fatty acids in TAGs (
A
Lingual, gastric lipase
9
Q
The breakdown of lipids depends on
A
length of fatty acids in the TAG
10
Q
Because lipids are not water soluble what must be done before lipase can digest the fatty acid
A
-Bile salts emulsify the lipids in the small intestine
- This allows the ester bonds of each lipid to orient toward the bile salt and be more open to lipase digestion
(note that colipase must bind the lipase to the particle to permit lipid degradation)
11
Q
What is emulsification
A
suspension into small particles in the aqueous environment
12
Q
Biles salts are ______ (have hydrophobic and hydrophilic components)
A
amphipathic
13
Q
Contraction of _____ to release bile salts and other pancreatic enzymes is stimulated by the gut hormone cholecystokinin
A
gallbladder
14
Q
Contraction of gallbladder to release bile salts and other pancreatic enzymes is stimulated by the gut hormone
A
Cholecystokinin
15
Q
Bile salts are synthesized from _____ in the ____-
A
cholesterol in the liver
16
Q
Emulsification of lipids greatly
A
increases the surface area of fats
17
Q
_____ is released in response to acidic material
A
secretin
18
Q
What is steatorrhea
A
production of bile salts is inadequate due to liver disease, large amount of fats (as much as 30g a day) are excreted in feces
19
Q
The release of secretin stimulates the release of
A
bicarbonate which increases the pH to 6, optimal for intestinal enzymes
20
Q
What is the optimal pH for intestinal enzymes
A
6
21
Q
Pancreatic lipase digests all lengths of FA. forms ____ and _____
A
Free fatty acids and 2-monoacylglycerol (2-MAG)
22
Q
The pancreas produces ____ which removes FA form cholesterol esters
A
esterase
23
Q
Esterase removes FA from
A
cholesterol esters
24
Q
Pancreas produces _____ which removes FA from phospholipids
A
phospholipase A2
25
Phospholipase A2 removes FA form
phospholipids
26
The use of fatty acids as fuel requires how many staging processes and what are they
3
First must be mobilized- TAGs are degraded to fatty acids and glycerol, which are released form the adipose tissue and transported to the energy-requiring tissues
second must be activated an transported into mitochondria for degradation
third- the fatty acids are broken down in a step-by-step fashion into acetyl CoA, which is then processed in the TCA
27
Short and medium chain FA (C4-C12) are absorbed into
intestinal epithelial cells
28
Short and medium chain FA (C4-C12) that are absorbed into intestinal epithelial cells enter straight into _____ and are transported into the ____ bound to serum ____
Portal blood, Liver, Albumin
29
Long chain FAs (13C-21C) and 2-MAGs are packed into _____ and emulsified by
micelles, bile salts before being absorbed into the walls of the small intestine
30
Lipids such as cholesterol, lyso PLs and fat soluble vitamins follow routes similar to
long chain FAs and 2-MAGs
31
Lipids are absorbed across ____, bile salts are left in the ____
microvilli, gut
32
once FA and MAGs are inside the intestinal cells they are condensed to form _____ (in smooth ER)
TAG
33
Once reassembled into TAG in the smooth ER of the intestinal cells lipids are packaged into
Chylomicrons
34
Chylomicrons are
lipoprotein transport particles: that contain Proteins (Apoprotein B48) and TAGs, fat-soluble vitamins, phospholipids, and cholesterol.
35
What is the main protein component of chylomicrons
Apoliprotein B-48
36
Protein constituents of lipoprotein particles are called
apolipoproteins
37
Chylomicrons are released into the
lymph system and then into the blood
38
in the resynthesis of TAGs in intestinal cells the first step is
The activation of Fatty acids
FA + ATP ------> FA-AMP + (CoASH) -----> FACoA + AMP
- in order to make TAG you must activate 2FAs
39
once the fatty acids are activated in the intestinal cells you can now undergo TAG synthesis and Nascent Chylomicron production. What are the steps?
2-Monoacylglycerol + FACoA ------> Diacylglycerol + FACoA ------> TAG + Apoprotein B48 + other lipids -----> Nascent chylomicrons
40
dietary FA are delivered to tissues in the form of
TAGs (they arrive at the tissues in the form of chylomicrons. They bind to membrane bound lipase and are degraded into free FAs and 2-MAG to enter cell)
41
Nascent chylomicrons are secreted by intestinal epithelial cells by
exocytosis
42
Nascent chylomicrons are secreted into the
lymphatic system
43
Nascent chylomicrons enter blood from lymphatic system via
thoracic duct
44
Nascent chylomicrons accept proteins from ____ within lymph and blood, which converts them into mature chylomicrons
HDL (high-density lipoprotein)
45
Nascent chylomicrons accept proteins from HDL (high-density lipoprotein) within lymph and blood, which converts them into
Mature chylomicrons
46
ApoE and ApoCII are what
very important lipoproteins
47
ApoE
is a very important lipoprotein that is recognized by receptors on surface of liver cells allowing for endocytosis (This allows for the remnants of chylomicrons to be taken up by liver and lysosomal enzymes within the hepatocyte digest the remnants, releasing the products into the cytosol)
48
ApoCII
Very important Lipoprotein that activates lipoprotein lipase present on capillary endothelial cells in muscle and adipose tissue which digests chylomicrons (this allows for the FA and 2-MAG to enter the cell)
49
Lipoprotein lipase is activated by
ApoCII
50
Chylomicrons can not go through
the plasma membrane
51
Lipoproteinlipae is located on
the surface of the cells (tissues)
52
TAGs in the chylomicrons are hydrolyzed by
lipoprotein on the surface of the cell(which is activated by ApoCII)
53
TAG are synthesized in adipocytes and stored in
lipid droplets
54
Utilization of FA as fuel requires how many steps and what are they
3,
mobilization
activation
degradation
55
Explain the 3 steps required for utilization of FA as fuel
1. ) mobilization: TAGs in adipose tissue are broken down to FA and glycerol, released and transported to energy requiring tissue
2. ) activation- the fatty acids must be active and transported into the mitochondria
3. ) degradation- stepwise breakdown of FA into acetyl CoA which is then processed in TCA cycle
56
Glucagon and epinephrine act on what adipocyte receptor for mobilization of fatty acids
7TM receptor
57
The 7TM receptor on adipocytes activates
adenylate cyclase
58
Adenylate cyclase
enzyme that catalyzes the conversion of ATP not cAMP
59
in mobilization of fatty acids from adipocytes increased levels of cAMP stimulates
activation of protein Kinase A
60
What is protein Kinase A role in mobilization of fatty acids from adipocytes
phosphorylates 2 key enzymes:
- Perilipin
- Hormone sensitive (HS) lipase
61
What is the role of perilipin activation in mobilization of fatty acids from adipocytes
The phosphorylation of perilipin has 2 major effects:
1. ) restructures fat droplet so that TAGs are more accessible to mobilization
2. ) Triggers release of a coactivator for adipose TAG lipase (ATGL)
62
once the coactivator binds to ATGL. ATGL
initiates the mobilization of TAGs by releasing a FA from TAG, forming diacylglycerol
63
diacylglycerol is covered into a FA and MAG by
Hormone-sensitive (HS) lipase
64
what is the role of MAG lipase
it produces FA and glycerol from MAG
65
MAG is converted to FA and glycerol by
MAG lipase
66
Chanarin-Dorfman syndrome
-coactivator for ATGL is missing or defective
- thus fats accumulate throughout the body
other symptoms include: dry skin (icythyosis), enlarged liver, muscle weakness, and mild cognitive disability
67
Epinephrine and glucagon induce
lipolysis
68
Fatty acids are not soluble in aqueous solutions. Thus in order to reach the tissues, the released fatty acids bind to
the blood protein albumin
69
Glycerol kinase is only found in
the liver
70
What enzyme catalyzes the reaction of glycerol to L-Glycerol 3-phosphate
Glycerol kinase (only found in the liver)
71
Glycerol and glycolytic intermediates are readily
interconvertible
72
in fatty acid oxidation the activation of the fatty acid occurs in the
cytoplasm (ER or outer mitochondrial membrane)
73
fatty acid oxidation occurs in the
mitochondrial matrix
74
The activation of a fatty acid is the
formation of a thioester linkage to a coenzyme A. using an ATP, coenzyme A, and the enzyme Acyl CoA syntheses (fatty acid thiokinase)
75
The activation of fatty acids occurs in how many steps. Explain
2.
first- the fatty acid reacts with ATP to form an acyl adenylate (in this mixed anhydride, the carboxyl group of a fatty acid is bonded to the phosphoric group of AMP)
second- sulfhydryl group of Coenzyme A attacks the acyl adenylate, which is tightly bound to the enzyme, to form acyl CoA and AMP
76
What makes fatty acid activation in fatty acid oxidation irreversible
The pyrophosphate is rapidly hydrolyzed by pyrophosphatase ( The hydrolysis of inorganic pyrophosphate makes biosynthetic reactions irreversible)
77
What traps Fatty acids in the cell and makes it metabolically active
fatty acid activation
78
Long chain fatty acids are conjugated to _____ to be carried from the outer mitochondrial membrane into the mitochondrial matrix
Carnitine
79
What catalyzes the reaction of ( Acyl CoA + carnitine -----> Acyl carnitine + HS-CoA)
Carnitine acyltransferase I (carnitine palmitoyl transferase I)
80
What catalyzes the reaction of (Acyl Carnitine + CoA ------> carnitine + Acyl CoA)
Carnitine acyltransferase II (carnitine palmitoyl transferase II)
81
What special properties does Carnitine have that make it thermodynamically feasible to carry fatty acids into the mitochondrial matrix
Zwitterionic nature (has both a positive and negative charge)
82
What shuttles acyl carnitine across the inner mitochondrial membrane
translocase
83
Carnitine acyltransferase I is located in
the outer mitochondrial membrane
84
Translocase returns carnitine back to the cytoplasmic mitochondrial side in exchange for
an incoming acyl carnitine
85
a saturated acyl CoA is degraded by a recurring sequence of ____ reactions. What are they?
```
4
Oxidation- by FAD
hydration
oxidation by NAD+
Thiolysis by Coenzyme A
```
86
The fatty acid chain is shortened by how many carbons as a result of the 4 degrading reactions
2
87
what is generated in each round of fatty acid oxidation
Acetyl CoA, NADH, FADH2
88
Fatty acid oxidation takes place at the
Beta carbon atom (thus the name Beta oxidation pathway)
89
the first reaction in each round of fatty acid degradation is the _____ of acyl CoA by an _________
oxidation, Acyl CoA dehydrogenase
90
Products of reaction 1 fatty acid degradation
Trans-enoyl CoA
| FADH2= 1.5 ATP
91
what is the enzyme in the reaction 2 of fatty acid degradation
Enoyl CoA hydratase
92
what is the enzyme in reaction 3 of fatty acid degradation
Hydroxy Acyl CoA Dehydrogenase
93
NADH2= how much ATP
2.5ATP in electron transport chain
94
What is the enzyme in the 4th reaction of fatty acid degradation
Thiolysis/ketothiolase (with a second molecule of Acetyl CoA)
95
The complete oxidation of palmitate yield ____ molecules of ATP
106 (note that the gross is 108 but the equivalent of 2 molecules of ATP are consumed in the activation of palmitate)
96
The degradation of palmitoyl CoA (C16-acyl CoA) requires how many reaction cycles
7 cycles. In the seventh cycle, the C4-ketoacyl CoA is thiolyzed to two molecules of Acetyl CoA
97
Unsaturated and odd chain FA degradation requires
2 additional enzymes
- Isomerase
- Reductase
98
_____ and ____ are required for the oxidation of unsaturated fatty acids
Isomerase and reductase
99
odd-chain fatty acid yield ______ and ____ in the final thiolysis step
Propionyl CoA and Acetyl CoA
100
propionyl CoA is converted into ___ before entering the TCA cycle and the conversion requires
Succinyl CoA (conversion requires vitamin B12 (a.k.a. Cobalamin)
101
If OAA is low (due to low carbs) acetyl CoA is
not utilized
102
Acetyl CoA combines with OAA to form
citrate
103
Acetyl CoA must combine with ____ to enter the TCA cycle
OAA
104
in fasting or diabetes, OAA is consumed to form ____by the _____ pathways
glucose, gluconeogenic pathway
105
When OAA is low then Acetyl CoA is diverted to the formation of
ketone bodies (acetoacetate and D-3-Hydroxybutyrate)
106
Acetoacetate is formed form acetyl CoA in how many steps
3
107
D-3 hydroxybutyrate is formed by the
reduction of acetoacetate in the mitochondrial matrix
108
Because it is a Beta-ketoacid, acetoacetate also undergoes a slow, spontaneous decarboxylation to
acetone (this is why the odor of acetone may be detected in the breath of a person who has a high level of acetoacetate in the blood)
109
The major site of production of ketone bodies (acetoacetate and 3-hydroxybutyrate) is in the
liver
110
in prolonged starvation, ____% of the fuel needs of the brain are met by ketone bodies
75%
111
Equation for utilization of Acetoacetate
Acetoacetate + Succinyl CoA + CoA transferase ----> Acetoacetyl CoA + CoA + thiolase ------> 2 Acetyl CoA
112
What is DKA
The lack or deficiency in insulin leads to glucose not being brought into cells. This means that while free fatty acids are still released there is none or low levels of OAA so Acetyl CoA can't enter the TCA cycle and is converted to ketone bodies. Ketone bodies are acid and cause pH to drop
