Fatty Acid: Synthesis & Storage Flashcards
(191 cards)
1
Q
where does fatty acid synthesis take place
A
cytosol
2
Q
for synthesis of fatty acids, where does it obtain the carbons for it
A
shuttled from mitochondria via citrate
3
Q
triacylglycerol synthesis is regulated by
A
insulin
4
Q
if there is a lack of insulin (diabetes), what does it result in regarding fatty acid synthesis
A
increased lipolysis
increased fatty acid oxidation
failure to synthesize fatty acids
5
Q
draw out the pathway of how insulin influences fatty acid synthesis and what direction it goes without insulingp
A
pg 5
6
Q
what is the primary FA factory
A
hepatocyte
7
Q
in FA synthesis how much ATP is contained in each acetyl CoA unit
A
10
8
Q
besides liver, what else participates in FA synthesis
A
adipocyte
skin
9
Q
glycolysis provides what 2 essential compounds for lipogenesis
A
Dihydroxyacetone-P
Pyruvate
10
Q
what is a major carbon source for lipogenesis
A
glucose
11
Q
what is function of Dihydroxyacetone-P
A
this becomes the scaffold that receives 3 fatty acids & becomes triacylglycerol – also TAG
12
Q
what is function of pyruvate in lipogenesis
A
after conversion to acetyl-CoA and citrate – provides building blocks for fatty acid synthase in the cytosol
13
Q
Acetyl CoA is shuttled from mitochondria to cytosol via
A
citrate
14
Q
what is Acetyl CoA produced from
A
AA’s or carbohydrate
15
Q
what breaks down citrate in cytosol
A
ATP-Citrate lyase
16
Q
draw out pathway of citrate leaving and entering mitochodnria/cytosol
A
pg 7
17
Q
pyruvate is decarboxylated to create
A
Acetyl CoA
18
Q
pyruvate is diverted and carboxylated to produce
A
pyruvate carboxylase
19
Q
Acetyl CoA + OAA with citrate synthase =
A
citrate
20
Q
cell’s high energy charge inhibits
A
Isocitrate dehydrogenase
21
Q
if Isocitrate dehydrogenase is inhibited, what happens
A
citrate accumulates and is exported via citrate shuttle
22
Q
draw out the “balancing act” of forming citrate in mitochondria from pyruvate
A
pg 8
23
Q
why is ATP needed for citrate lyase to break citrate into acetyl CoA & OAA
A
citrate is stable & energy needed to break bonds
24
Q
pyruvate recycling produces add’l
A
NADPH
25
if there is insulin and enough energy you will produce
fat
26
what pathway is needed to produce fat
PPP (pentose phosphate pathway)
27
what is rate limiting step of fatty acid synthesis
ACC (acetyl CoA Carboxylase)
28
what enzymes require biotin
ACC
pyruvate carboxylase
propinyl coA
29
prostaglands are
hormones
30
prostaglands require
fatty acid
31
what kind of fatty acid do we need from diet
omega 6
32
to accumulate citrate have to stop or slow down
TCA cycle
33
How many carbons in Lauric acid
12 and 0 unsaturated
34
how many carbons in Myristic acid
14 and 0 unsaturated
35
how many carbons in Palmitic acid
16 and 0 unsaturated
36
how many carbons in Stearic acid
18 and 0 unsaturated
37
what are the two main ways NADH is produced
PPP
| malic enzyme
38
describe how PPP makes NADH
The oxidative component of the pentose phosphate pathway two dehydrogenases allows the production of NADPH
39
describe how malic enzyme makes NADH
Malic enzyme recycles malate into pyruvate and in the process produces NADPH
40
production of NADPH is essentia for
fatty acid biosynthesis
41
what are the two dehydrogenases in PPP that produce NADPH
glucose 6 phosphate dehydrogenase and 6-phopogluconate dehydrogenase
42
what is a three carbon intermediate of acetyl coA
malonyl CoA
43
when enzyme is needed for acetyl coA → malonyl coA
Acetyl-CoA carboxylase
44
carboxylation requires
biotin
45
biotin deficiency has what symptoms
gastrointestinal upset, dermatitis, alopecia, paraesthesia and muscle ache.
46
what is the major regulatory step to produce fatty acids
acetyl coa → malonyl coa
47
acetyl coa → malonyl reaction, what is needed
biotin
CO2
ATP
48
what are the 4 enzymes that require biotin
propionyl coenzyme A (CoA) carboxylase (PCC), pyruvate carboxylase (PC), β-methylcrotonyl CoA carboxylase (β-MCC), and acetyl CoA carboxylase (ACC).
49
what interfere with ingestion of biotin
avidin
50
where is avidin found
raw egg whites
51
what is allosteric activatory of acetyl CoA carboxylase?
citrate
52
what is allosteric inhibitor of acetyl CoA carboxylase?
palmitoyl CoA
53
how does citrate promote activity of acetyl coA carboxylase
induction of polymerization and gene expression
54
how does Palmitoyl-CoA inhibit activity of acetyl CoA carboxylase?
inhibits activity and induction via promoting depolymerization
55
what does by AMP-protein kinase (AMPK) do to acetyl coA carboxylase
inactivates
56
how does AMP protein kinase inactivate Acetyl CoA carboxylase
phosphorylation
57
with high levels of ATP what happens to acetyl CoA Carboxylase
Dephosphorylation, activated
58
describe the structure of fatty acid synthase
solid-state dimer of two multi-function monomers
| symmetrical
59
Acyl carrier protein’s function holds growing acyl group with what bond?
thioester bond
60
with how many carbons does fatty acyl chain grow
2
61
how many carbons is palmitate acid
16
62
what donates carbons for growing chain of fatty acid
activated malonate
63
draw comparison of oxidative degradation & FA synthesis
pg 16
64
there is no free intracellullar palmitate, it exsits as
palmitoyl-CoA
65
what inhibits translocation of fatty acids to mitochondria
malonyl CoA
66
when lipogenesis is happening what does malonyl CoA do to ß oxidation
shut it down
67
where are FA elongated
ER
68
what is carbon source for FA elongation
malonyl CoA
69
what is used for reducing power for FA elongation
NADPH
70
what is the major difference b/w elongation of fatty acids and synthesis
in elongation: growing acyl chain is joined by thioester bonds to CoASH instead of ACP
71
what are two fatty acids we cannot synthesize
18:2 linoleic (Ω-6) and& 18:3 linolenic (Ω-3)
72
mammals cannot insert double bonds beyond what point
C9-10
73
draw out the Desaturation of a fatty acid by fatty acyl-CoA desaturase
pg 21
74
where does desaturation of FA take place
lumenal side of smooth ER
75
describe characterisitc of cytochrome P450 enzymes
located in themembrane endoplasmic reticulum and uses NADPH and O2.
76
fatty acyl-CoA desaturase is a member of what family
cytochrome P450
77
linoleic acid gives rise to
arachidonic acid
78
what is a vital component in the water barrier in skin
ceramide
79
in making a FA, after a desaturation then what
elongation of 2 Cs then another desaturation
80
arachidonic acid is needed as a major component of
water barrier in skin
81
what does PUFA stand for
polyunsaturated fatty acids
82
essential fatty acids are
Ω-3 and Ω-6
83
what is Ω-3
linolenic acid
84
what is Ω-6
linoeic acid
85
what is Alpha(α)-linolenic acid converted to
eicosapentaenoic acid & docosahexaenoic acid
86
the final step in docosahexaenoic acid synthesis is
peroxisomal β-oxidation to remove the 2-carbon acetyl-CoA from the 24:6 fatty acid called tetracosahexaenoic acid
87
what enzymes allow alpha linoleic acid to convert to EPA & DHA?
microsomal ER enzymes
88
what cells synthesize triglycerides
basically all of them
89
what activate free FA
CoASH
90
TAG stands for
triacylglyceride
91
TAG synthesis usually begins with
glycerol
92
what is first step to make TAG
glycerol phoshporylated
93
what enzyme phoshporylates glycerol in first step to make TAG
glycerol kinase
94
after glycerol is phosphorylated, what happens in TAG synthesis
activated fatty acids serve as substrates for fatty acid addition
95
in adipose tissue there is no expression of
glycerol kinase
96
since there isn't glycerol kinase in adipose tissue, what is used to make Tag
DHAP (from glycolysis)
97
draw pathway for TAG synthesis in other tissues, adipocytes, and intestinal enterocytes
pg 24
98
insulin stimulates conversion of excess glucose to
glycogen & TAG
99
what does VLDL stand for
very long density lipopotrein
100
what enzyme is needed to breakdown TAG
lipoprotein lipase
101
during fasting, TAGs assembled in liver are loaded into
VLDL particles
102
where does VLDL assembly begin
RER
103
what does APO B-100 do
assembles core of phospholipids
| mediate TG delivery at specific tissue destinations
104
VLDL is seceted into blood for what purpose
tissues have access to cholesterol and fatty acids
105
LPL stands for
lipoprotein Lipase
106
LPL is attached to
capillary wall
107
what activates LPL
apoprotein CII
108
what inhibits LPL
Apo CIII
109
TAG's are hydrolyzed by
LPL
110
inside cells fatty acids are activated with
CoASH
111
what happens to FA to store them as TAGs
esterified
112
what is the difference b/w VLDL & chylomicrons?
chylomicrons comes from the lipids in the diet, that cholesterol and TAGs while VLFL are TAGS and cholesterol produced by the liver.
so basically chylomicrons = diet
VLDL = we make it
113
what holds LPL to capillary wall
heparan sulfate tether
114
LPL requires activation by
Apoprotein CII
115
how does NADH production make sense? how does it help us?
needed to fuel fatty acid biosynthesis
116
describe acetyl coa regulation
acetyl coA needs to accumulate but not so much to inhibit pyruvate DH
needs careful regulation
117
biotin deficiency symptoms related to
fatty acid synthesis
| propionyl coA
118
propionyl coA is important for the
brain
119
what does enzyme do to acetyl coA carboxylase
activates by dephosphorylating
120
acetyl coa carboxylase when it is monomer vs polymer when is it active vs. inactive
monomer: inactive
polymer: active
121
FAS monomers contain covalently bound
phosphopantotheine
122
phosphopantotheine is what
vitamin
123
phosphopantotheine is bound to what residuc of ACP on FAS (fatty acid synthase)
serine
124
phosphopantotheine is attached to the FAS protein itself via
serine
125
tRNA occupies t and a site. on a site have free amino group b/c using carboxylic group. amino group nucleophilic attack that will attack ester bond in t site to form peptide bond. moves to a site and become t site (not sure if he is saying t or p)
first is terminal last one removed is ???
help
126
ACP site and cysteine site
moved from ACP to other site ???? pg 14
127
FA biosynthesis and ß oxidation
are similar, basically just opposite
128
Acetyl-CoA + 7 Malonyl-CoA + 14 NADPH + 14 H+yields
Palmitate + 7 CO2 + 14 NADP+ + 8 CoASH;
| add 8 ATP (for citrate lyase)
129
Palmitate + 7 CO2 + 14 NADP+ + 8 CoASH;
| add 8 ATP (for citrate lyase) comes from
Acetyl-CoA + 7 Malonyl-CoA + 14 NADPH + 14 H+yields
130
The cytosolic produced 16 carbons, palmitoyl CoA is translocated to the ER so elongase enzyme activity extends it to 18 carbon units called
estearic acid.
131
draw out Oxaloacetate & acetyl coa crossing cytosol
pg 9
132
look at sequence of events during synthesis of fatty acid
pg 14
133
omega 6 in diet comes in what form
linoelic acid (omega 6)
134
desaturase is located where
ER
135
ALA stands for
Alpha(α)-linolenic acid
136
VLDL is from liver and equivalent to
chylomicron
137
protein in chylomicron to help is
Apoprotein B 48
138
protein in VLDL to help is
Apoprotein B 100
139
VLDL is source of
LDL
140
LDL comes from
VLDL
141
chylomicrons are present in what state
well fed
142
VLDL are present in what state
fasting
143
Apo CIII is
inhibitor of lipoprotein lipase
144
pts whoh ave GOF of Apo CIII what happens
packing of LPL is inhibited. it interferes with assembly of triacylglycerides in VLDL and it goes back to liver and they start to get liver problems and have fatty liver which is precursor to diabetes type II
145
how is glucose trapped and controlled in liver without insulin signaling (how do we control glucokinase?)
glucokinase is trapped in the nuclei
146
write out the comparison/contrast of synthesis and degradation & understand
pg 17
147
when adipocytes are too big what happens
they attract attention of marophages which interfere with insulin signaling
148
what is the initial acceptor of fatty acids during TAG synthesis?
Glycerol-3-phosphate
149
during the well fed state what do liver and adipoctyes use to produce glycerol-3-phosphate
glycolysis intermediate: dihydroacetone phosphate (DHAP)
150
the liver contains glycerol kinase, what does this enzyme do
phosphorylate glycerol and produce glycerol-3-phospahte
151
in glycerol, position 2 has what kind of fatty acid
unsaturated
152
what process is used by adipocytes to form TAGs
Glyceroneogenesis
153
what stimulates lipolysis
glucagon & EPI
154
during lipolysis what is inhibited
glycolysis
155
Glyceroneogenesis is essentially an abbreviated version of
gluconeogenesis
156
glycerol 3-phosphate is needed for synthesis of
triacylglycerol
157
draw pathway for Glyceroneogenesis
pg 29
158
about 75% of FA released by lipolysis, what happens to it
resterfied to reform TAGs instead of being used for fuel
159
what regulates the levels of PEP carboxykinase
cortisol
160
how does liver send TAG to blood?
in VLDL
161
what is the "Leash" of FA release
insulin
162
if insulin is weak or not working correctly what hapens to FA release
insulin is the "leash" so glucagon has a higher role and FA is released at higher rate/amount
163
what does FOX01 do
TF that controls gluconeogenesis in genes
164
what is the result of insulin on SREBP's
insulin activates them - they are very sensitive to insulin
165
draw the pathway of insulin affect on SREBP-1c
bottom right pg 31
166
draw the effect of insulin and glucose on different TF
pg 31 left side
167
describe how hyperinsulemia precedes diabetes
an obese person before they are diabetic will have increased insulin resistance. this will continue until eventually their pancreas cannot keep up with demand, and then insulin levels will drop and they will have hyperglycemia
168
what does insulin do to activate glycogen synthesis
it activates glycogen synthase via Akt2
169
what does insulin do to decrease gluconeogenesis?
inactivates FOX01
170
what promotes activation of SREBP1
insulin signaling
171
what activates ChREBP
liver when metabolized
172
SREBP1 and ChREBP both promote
de novo lypogenesis
173
what does insulin do to adipose tissue
inhibits lipolysis & promotes glucose uptake
174
if there is more glucose entering the cell what pathway will be increased
PPP
175
If PPP pathway is increased (too much glucose entering) then what is there increased levels of
xylulose-5-phosphate
176
xylulose-5-phosphate does what to ChREBP
it activates PP2Aδ which will then remove the inhibitory phosphorylations on ChREBP in cytosol and nucleus
177
ativation of LXRα results in
increased expression of ChREBP in liver
178
draw out ChREBP pathway and its role in lipid & glucose homeostasis
pg 34
179
draw out and explain the main mechanisms of insulin resistance
pg 35
180
Increased intracellular diacyglycerols lead to activation of
PKC-θ and PKC-ε in skeletal muscle and liver (respectively)
181
activation of PKC-θ in muscle will lead to
decreased muscle glycogen synthesis, owing to reduced insulin-stimulated GLUT4 translocation to the plasma membrane.
GLUT4 won't work as well so more glucose in blooddraw
182
activation of PKC-ε in liver will lead to
decreased hepatic glycogen synthesis, owing to decreased activation of glycogen synthase, and increased hepatic gluconeogenesis
183
draw out basic cellular insulin resistance in muscle
pg 36
184
draw out basic cellular insulin resistance in liver
pg 36
185
draw insulin receptor with insulin sensitivy and insulin resistant
pg 37
186
draw insulin receptor pathway
pg 37
187
draw insulin sensitive liver
pg 38
188
draw insulin resistant/type II diabetes liver
pg 38
189
draw prediabetes liver
pg 38
190
draw type II diabetes liver
pg 38
191
review concept key
pg 39
