WK1_5 Alternative Fatty Acid Oxidation / Fatty Acid Synthesis and Metabolism Flashcards
1
Q
fatty acid (FA) metabolism couples to central metabolic pathways through..
A
Acetyl-CoA
2
Q
free fatty acids (FA) can be taken up by most tissue and used as energy source except.. (2)
A
brain and RBCs
3
Q
greater 90% of FA in plasma are esters (_____, _____, and ______)
A
TAGs, cholesterol esters, phospholipids
4
Q
does saturated FA have double bonds?
A
no
5
Q
does unsaturated FA have double bonds?
A
yes
6
Q
between the 2 double bonds present in unsaturated FA, which one is natural?
A
cis
7
Q
trans double bonds are produced as by-product of _____
A
hydrogenation
8
Q
which double bond is solid at body temperature?
A
trans
9
Q
in FA nomenclature, carboxylate is numbered as carbon #_
A
1
10
Q
in FA nomenclature, number before colon represents..
A
length of chain
11
Q
in FA nomenclature, number after colon represents..
A
how many double bonds
12
Q
in FA nomenclature, numbers in parentheses represents..
A
positions in unsaturation
13
Q
carbon at methyl terminus is the ______ carbon
A
omega
14
Q
FA biosynthesis occurs primarily in the..
A
liver cytosol
15
Q
T/F mitochondrial Acetyl-CoA cannot be exported to the cytosol
A
TRUE
16
Q
acetyl moiety enters ctyosol as _____ following condensation with oxaloacetate
A
citrate
17
Q
acetyl moiety enters cytosol as citrate following..
A
condensation with oxaloacetate
18
Q
regulation of transport is via [?], which is high under the fed state
A
[citrate]
19
Q
regulation of transport is via [citrate], which is high under the _____ state
A
fed state
20
Q
during fed state, large amounts of ATP inhibit _____ in TCA cycle
A
isocitrate dehydrogenase
21
Q
oxaloacetate is transported back into _____ through transporters, permuting efficient cycle of transfer of acetate into cytosol
A
mitochondrila matrix
22
Q
regulation of fatty acid biosynthesis is through..
A
Acetyl-CoA carboxylase
23
Q
biotin mediates carboxylation of acetyl ova through a ______ type of mechanism
A
swinging arm
24
Q
insulin activates through…
A
phosphatase activation
25
insulin activates through phosphatase activation (______)
fed state
26
insulin-dependent activation of Acetyl-CoA carboxylase ______ fatty acid biosynthesis
upregulates
27
FA synthesis occurs in the ______ and uses ______
cytosol; NADPH (not NADH)
28
FA is cleaved by..
palmitoyl thiesterase
29
further ______ and ______ of FA occurs in smooth ER
elongation; desaturation
30
carbon skeleton rearrangements set enzyme up for next..
condensation
31
2 carbon acetate condenses with Malonyl-CoA, with release of..
carbon dioxide
32
______ enhances availability of extracellular fatty acids to permit adipose tissue uptake and formation of TAGs
insulin
33
LPL _____ FA on TAGs in chylomicrons
hydrolyzes
34
______ transport FA
adipocytes
35
______ is basic building bock for TAG synthesis
glycerol
36
in _____, glycerol kinase phosphorylates glycerol released following delivery of FA to adipose tissue
liver
37
synthesis of TAG involves activation of FA by _____ and _____
CoA-SH; sequential condensation
38
_____ mobilizes fats (TAGs) in adipose tissue
epinephrine
39
_____ blocks lipolysis through activation of phosphodiesterase (hydrolysis of cAMP) to enhance synthesis of fats
insulin
40
mobilization of FA reserves in adipocytes is initiated by _____
hormone sensitive lipase
41
hormonal activation of cAMP-dependent protein kinase through _____
adenylate cyclase
42
phosphorylation of lipase initiates TAG _____
degradation
43
phosphorylation of acetyl CoA carboxylase _____ FA synthesis
inhibits
44
glycerol is released and transported to liver for _____
reuptake
45
FA transported to tissues in complex with..
albumin
46
beta oxidation of fatty acids occurs in ______
mitochondrial matrix
47
FA is activated by conjugation with..
HS-CoA
48
what kind of molecule is carnitine?
carrier molecule
49
FA acyl chain is transferred to carnitine by..
carnitine palmitoyl transferase
50
malonyl CoA _____ carnitine palmitoyl transferase preventing FA synthesis from occurring simultaneously as oxidation
inhibits
51
net production of _____ ATP per palmitate oxidized
129
52
formation of ketone bodies arise from elevations in..
lacetyl-CoA
53
where does ketone body formation occur?
in liver
54
formation of CoA allows..
FA oxidation
55
ethanol metabolism involves formation of _____, and can deplete _____ needed for glycolysis
NADH; NAD+
56
excess NADH causes metabolic disorders, including inhibition of _____ and _____
TCA cycle; FA oxidation
57
accumulation of FA in liver can result in fatty liver (_____)
steatosis
58
metabolism of ethanol results in large increases in..
NADH
59
_____ is _inhibited due to depletion of oxaloacetate
TCA cycle
60
_____ is inhibited due to depletion of pyruvate
gluconeogenesis
61
_____ is inhibited due to depletion of NAD+
glycolysis
62
```
which of the following lipid designations corresponds to stearic acid (sterate)?
A) 16:0
B) 16:1
C) 18:0
D) 18:1
E) 20:4
```
C: stearic acid has 18 carbons and fully reduced
63
what molecule acts as the carbon carrier to move acetyl CoA across the mitochondrial membrane for fatty acid biosynthesis?
citrate
64
which cofactor/vitamin is used to transfer carboxylate moieties?
biotin
65
which apolipoprotein acts to transport lipids from the liver to peripheral tissues?
VLDL
66
alcoholism typically requires consumption of 30-50% of total calories as ethanol, and is commonly associated with increases in which metabolite?
ketone bodies + NADH
67
what are the functions of cholesterol?
- structural component in membranes
| - precursor of bile acids/steroid hormones/vitamin D
68
what are the regulations of cholesterol?
- liver plays central role in regulating cholesterol availability
- cholesterol precipitates along endothelial lining of blood vesicles (plaque formation ) contributing to cardiovascular disease
69
_____ catalyzes rate limiting step of cholesterol biosynthesis
HMG CoA reductase
70
_____ provides all carbons for cholesterol biosynthesis
acetate
71
T/F all nucleated cells can make cholesterol
TRUE
72
familial hypercholesterolemia results in..
deposition of cholesterol
73
HMG CoA reducatase catalyzes..
the rate liming step of cholesterol biosynthesis
74
cholesterol is precursor to..
bile acids, steroid hormones, and vitamin D
75
most plasma cholesterol is _____ (at alcohol) with fatty acid to enhance hydrophobicity
esterified
76
T/F cholesterol is synthesized by all tissues
TRUE
77
T/F HMG CoA reductase activity is regulated by extracellular cholesterol (LDL) in patients homozygous for FH
FALSE. HMG CoA reductase activity is NOT regulated by extracellular cholesterol (LDL) in patients homozygous for FH
78
HMG CoA redutase activity _____ in normal cells deprived of LDL
increases
79
addition of extracellular LDL _____ HMG CoA reductase activity in normal cells but not FH patients
inhibits
80
what suggests a receptor for LDL?
high-affinity association (Kd=nM)
81
LDL particles bind to surface, but _____, in some patients homozygous for FH
NOT internalized
82
LDL receptor internalization is mediated by..
clathrin coated pits
83
T/F cystoplasmic portion of LDL receptor has ability to bind a range of lipoprotein particles of varying size and composition
TRUE
84
flexible linkers connect..
adjacent ligand binding modules
85
_____ directs LDL receptor to coated pit for internalization
Asn-Pro-Val-Tyr
86
what is required to liberate cholesterol esters?
lysosomal mediated degradation of LDL receptor
87
what blocks LDL-dependent regulation of HMG CoA reductase (blocks acidification of lysosome)?
chloroquine
88
delivery of cholesterol to golgi transcriptionally _____ HMG CoA reductase and LDL receptor
down regulates
89
upon cholesterol depletion, sterol regulatory element-binding protein (SREPB) is transported to..
golgi
90
in golgi, proteolysis occurs by _____ to generate activated transcription factor (SREBP) in nucleus, which transcriptionally up regulates LDL receptor protein, HMG CoA reductase, and genes encoding all 26 steps in cholesterol biosynthesis
SCAB (SREBP cleavage activating protein)
91
_____ selectively inhibit HMG CoA reductase to lower plasma cholesterol
statins
92
statins are taken up by _____ to block HMG CoA reductase
liver
93
decreases in liver cholesterol _____ the transcription of both HMG CoA reductase and _____
upregulate; LDL receptors
94
newly produced LDL receptors sequester additional cholesterol from _____
blooe
95
_____ is digested and _____ is released fro liver metabolism
LDL; cholesterol
96
statin _____ synthesis of liver cholesterol
prevents
97
_____ maintain cholesterol necessary for liver function
LDL receptors
98
_____ patients have large accumulation of cholesterol in lysosomes
Neumann-Pick C
99
HDL is taken up through _____
receptor mediated endocytosis
100
_____ disease arises from defects in NPC2 and NPC1
NewmanPick
101
_____ and _____ work together to extract cholesterol and delivery cholesterol to membrane
NPC2; NPC1
102
LDL receptors act to mediate....
transport of extracellular apolipoprotein complexes through endocytosis via clathrin coated pits
103
statins are competitive inhibitors of which enzyme?
HMG CoA reductase
104
which tissue/organ primarily takes up dietary fats carried by chylomicrons?
adipose tissue & muscle
105
fatty acid metabolism couples to central metabolism through...
formation of acetyl-CoA
106
all tissues, except _____ and _____, can use fatty acids as energy
brain and mature RBCs
107
why can't the brain use fatty acids as the blood brain barrier block transport?
because free fatty acids are actually bound to albumin, which is too big to cross blood-brain barrier in healthy people
108
_____ have no mitochondria, and cannot metabolize acetyl-CoA
mature RBCs
109
[LIKELY HIGH YIELD] cis-double bonds create a _____ that disrupts the acyl chain packing
kink
110
kink acts to..
increase fluidity
111
in fats (TAGs) kinks change the...
phase transition temperature
112
trans-fatty acids are created as a byproduct of...
hydrogentation
113
hydrogenation is an industrial mechanism to _____ double bonds and _____ the shelf life of fats
reduce; increase
114
double bonds are sites of _____, as there provide a site for oxygen reactivity
oxidation
115
_____ bonds pack very well together (have a high _____), and are often thought to be hard to metabolize and to promote artherosclerosis
trans-double bonds; phase transition
116
biosynthesis occurs principally in...
cytosol
117
building blocks for FA biosynthesis arises from
Acetyl-CoA
118
only in the presence of excess _____ ( when energy needs of cellar met), is FA synthesis activated
citrate
119
[LIKELY HIGH YIELD] what is the regulated step of FA biosynthesis?
acetyl CoA carboxylase
120
_____ signals a fed state
insulin
121
insulin _____ FA biosynthesis through the regulation of acetyl CoA carboxylase
activates
122
_____ is involved in transfer of carboxylates
biotin
123
biotin involves a _____ mechanism that moves between the 2 active sites involved in carboxylation of biotin and transfer of the carboxylate to acetyl CoA to form malonyl CoA
swinging arm mechanism
124
biotin inolves a swinging arm mechanism that moves between the 2 active sites involved in.. (2)
1) carboxylation of biotin
| 2) transfer of the carboxylate to acetyl CoA to form malonyl CoA
125
inactivation of acetyl CoA carboxylase involves..
AMP or phosphorylation of AMPK (AMP-activated kinase)
126
AMPK i sunder the control of _____ or _____, which both indicate a need for cellular energy
glucagon or epinephrin
127
FA biosynthesis involves enzyme FA synthase, which acts to form..
palmitate
128
transfer of acetyl CoA is energetically _____, as the thioester bond in acetyl-CoA is maintained on the enzyme
favorable
129
the ______ in malonyl CoA is maintained following transfer to the enzyme
thioester bond
130
FA synthase has 7 distinct catalytic sites that permit the highly efficient catalysis of a..
palmitate
131
insulin-dependent up regulation of lipoprotein lipase acts to..
shift metabolism to promote FA uptake by adipose tissue
132
glycerol can be made from _____ or from _____
glycolytic intermediates; absorbed glycerol
133
formation of ester bonds requires an activation step, which involves..
formation of a thirster born with CoA
134
mobilization of fats is opposed by _____, which activates a phosphodiesterase that hydrolyzes cAMP
insulin
135
_____ promotes mobilization of fats through activation of hormone sensitive lipase, which hydrolyzes a single phosphoester linkage
epinephrine
136
where does beta oxidation o FAs occur?
in the mitochondrial matrix
137
critical to oxidation is the regulated transfer of activated FAs which permits the transfer of the FAs to _____ for transport into the mitochondrial matrix
carnitine
138
malonyl CoA _____ transport of FAs into the mitochondrial matrix for beta-oxidation
inhibits
139
what is formed by the spontaneous breakdown of acetoacetic acid?
acetone
140
acetone is _____, and is commonly smelled on breath
volutile
141
acetoacetic acid and beta-hydroxybutryic acid are both _____ and their formation regenerates the _____ needed for further FA degradation
water soluble; CoA-SH
142
ketones bodies are highly _____, and cross the blood brain barrier, providing a source of energy for the brain
soluble
143
ketone bodies arise from elevations in _____
acetyl-CoA
144
almost all ketone bodies arise from _____
FA degradation
145
depletion of NAD+ limits ability to carry out..
glycolysis
146
excess NADH inhibits _____ and _____
TCA cycle; FA oxidation
