1When blood glucose levels are high, beta cells of the pancreas are triggered to produce an anabolic hormone,
When blood glucose levels are high, beta cells of the pancreas are triggered to produce an anabolic hormone, insulin
2Insulin stimulates mainly in the liver.
Insulin stimulates fatty acid synthesis mainly in the liver.
3Under aerobic conditions, glucose is oxidized, a process that results in the production of inside the
Under aerobic conditions, glucose is oxidized, a process that results in the production of acetyl CoA inside the mitochondrial matrix.
4 a two-carbon compound is the precursor that is required for fatty acid synthesis.
Acetyl CoA a two-carbon compound is the precursor that is required for fatty acid synthesis.
5Fatty acid synthesis occurs in the
Fatty acid synthesis occurs in the cytosol.
6What are the two compounds required for fatty acid synthesis?
1.
2.
What are the two compounds required for fatty acid synthesis?
1. Acetyl CoA (substrate)
2. NADPH (reductant)
7The precursor acetyl CoA be transported directly from the mitochondria into the cytosol, due to the .
The precursor acetyl CoA cannot be transported directly from the mitochondria into the cytosol, due to the absence of a transport system for acetyl CoA.
8Transport of acetyl CoA into cytosol?
Citrate is carried into the cytosol by a citrate carrier. Then, (enzyme) converts citrate into and . + converts to . (which produces ) converts malatae into . Pyruvate can then enter the mitochondria using a pruvate transporter. Using and ), pyruvate becomes OAA. The OAA can then be combined with using to form citrate.
Transport of acetyl CoA into cytosol?
Citrate is carried into the cytosol by a citrate carrier. Then,
citrate lyase (+COA) (enzyme) converts citrate into
OAA and
acetyl CoA.
Malatae dephydrogenase +
NADH converts
OAA to
malatae.
Malic enzyme (which produces
NADPH) converts malatae into
pyruvate + CO2 . Pyruvate can then enter the mitochondria using a pruvate transporter. Using
pyruvate carboxylase and
ABC (ATP, Biotin, CO2), pyruvate becomes OAA. The OAA can then be combined with
acteyl CoA using
citrate synthase to form citrate.

9In addition to acetyl CoA, fatty acid biosynthesis
also requires a
In addition to acetyl CoA, fatty acid biosynthesis
also requires a reductant NADPH.
10What are the sources of NADPH for fatty acid synthesis?
1.
2.
What are the sources of NADPH for fatty acid synthesis?
1. Hexose monophosphate shunt (Major source)
2. Malic acid oxidation
11What is the rate limiting step and commited step in fatty acid synthesis?
What is the rate limiting step and commited step in fatty acid synthesis?
Acetyl CoA carboxylase
12Acetyl CoA carboxylase has
moiety which participates in the
carboxylation reaction in forming
Acetyl CoA carboxylase has covalently bound biotin (one of the vitamin B derivative)
moiety which participates in the
carboxylation reaction in forming
malonyl CoA.
13Steps in Synthesis of Malonyl COA
1. Carboxylation of
+ + ->
2. Carboxylation of
+ -> +
Steps in Synthesis of Malonyl COA
1. Carboxylation of biotin
HCO3- + ATP + Biotin -> Carboxy Biotin
2. Carboxylation of acetyl CoA
Carboxy biotin + Acetyl CoA -> Malonyl CoA + biotin
14Consumption of raw egg is not
recommended since raw egg
contains a protein called
which can tie up the which would adversely impact
Consumption of raw egg is not
recommended since raw egg
contains a protein called avidin
which can tie up the biotin which would adversely impact acetyl CoA carboxylase
15What three things does acteyl CoA carboxylase need?
1.
2.
3.
What three things does acteyl CoA carboxylase need?
1. ATP
2. Bicarbonate
3. Acetyl CoA
16Acetyl CoA carboxylate synthesizes
Acetyl CoA carboxylate synthesizes malonyl CoA
17 is a committed metabolite that can enter only the fatty acid biosynthetic
pathway.
Malonyl CoA is a committed metabolite that can enter only the fatty acid biosynthetic
pathway.
18Fatty acid synthase (FAS) is a multi-enzyme complex that is
composed of domains that are
Fatty acid synthase (FAS) is a multi-enzyme complex that is
composed of seven catalytic domains that are covalently
linked
19What are the three steps of the catalytic events of the fatty acid synthase (FAS)?
1. After condensation, acteoacteyl group is reduced to in 3 steps while still attached to
2. The is transferred to and enters and gets attached to
3. occurs again and new 6 carbon gets while attached to
4. Cycle repeats until
What are the three steps of the catalytic events of the fatty acid synthase (FAS)?
1. After condensation, acteoacteyl group is reduced to
butyrl group in 3 steps while still attached to
ACP (acyl carrier protein) 2. The
butyl group is transferred to
condensing enzyme and
new malonyl group enters and gets attached to
acp 3.
Condensation rxn occurs again and new 6 carbon gets
reduced while attached to
ACP 4. Cycle repeats until
C-16 
20Order of Enzyme Domians
Order of Enzyme Domians
AT
MT
CE
KR
DH
ER
TE
21What is AT?
acetyl transferase
22What is MT?
malonyl transferase
23What is CE?
Keto synthase (condensing enzyme)
24When blood glucose levels are high, beta cells of the pancreas are triggered to produce an anabolic hormone,
When blood glucose levels are high, beta cells of the pancreas are triggered to produce an anabolic hormone, insulin
25What is ER?
Enoyl reductase (USES NADPH)
26What is KR?
b-ketoacyl reducatse (uses NADPH)
27What is TE?
Thioesterase (releases palmitate from palmitoyl- ACP) ***ACP
28 is the prosthetic group that
anchors the growing fatty acid chain during synthesis
phosphopantetheine (a derivative of the vitamin pantothenate) is the prosthetic group that
anchors the growing fatty acid chain during synthesis
29 Phosphopantetheine is covalently attached to protein
5’-Phosphopantetheine is covalently attached to ACP protein
30NADPH is utilized in the
NADPH is utilized in the reduction reactions.
31 domain cleaves off the final product, , from the fatty acid
synthase enzyme complex. Occasionally the fatty acyl chain goes through one more cycle, and
it gets cleaved off as
Thioesterase I domain cleaves off the final product, palmitate (C16), from the fatty acid
synthase enzyme complex. Occasionally the fatty acyl chain goes through one more cycle, and
it gets cleaved off as stearic acid (C18)
32In mammals during lactation, mammary glands express , an independent protein that interacts with the fatty acid synthase complex and causes the of fatty acids , , and
In mammals during lactation, mammary glands express Thioesterase II, an independent protein that interacts with the fatty acid synthase complex and causes the premature release of fatty acids (capric (C10), Lauric (C-12), and myristic (C14)
33Unsaturated fatty acids that can be synthesized de novo are called
Unsaturated fatty acids that can be synthesized de novo are called non-essential fatty acids
34Humans do not have
enzymes that can introduce beyond
Humans do not have
enzymes that can introduce cis
double bonds beyond carbons 9 to
10
35Stoichometry of palmitate synthesis
36Polyunsaturated fatty acids linoleic, 18:2
(9,12) and linolenic,18:3 (9,12,15) are
therefore that must be
supplied in the diet.
Polyunsaturated fatty acids linoleic, 18:2
(9,12) and linolenic,18:3 (9,12,15) are
therefore essential fatty acids that must be
supplied in the diet.
37Linoleic acid is the precursor for the
biosynthesis of which is
.
Linoleic acid is the precursor for the
biosynthesis of arachidonic acid which is
C-20:4 (5,8,11,14).
38 the end product of fatty
acid synthase can be further elongated
and/or desaturated by separate enzymes
that are located in the and
.
Palmitate (16:0) the end product of fatty
acid synthase can be further elongated
and/or desaturated by separate enzymes
that are located in the mitochondria and
endoplasmic reticulum.
39The desaturase that is located in the
endoplasmic reticulum using , , and forms or respectively.
The desaturase that is located in the
endoplasmic reticulum using molecular
oxygen, NADPH, and palmitoyl CoA or stearoyl CoA forms palmitoleic acid, 16:1 (9) or oleic acid 18:1 (9) respectively.
40The reaction that takes place with the desaturase in the ER uses a complex of which three membrane bound enzymes?
(NADH-cytochrome b5 reductase, cytochrome b5, and a desaturase)
41Draw desaturase reaction
42Electron Transport Chain reaction in the desaturation of
Electron Transport Chain reaction in the desaturation of stearoyl CoA
43Triglycerides are synthesized in the liver and are
stored in
Triglycerides are synthesized in the liver and are
stored in adipose tissues.
44Acetyl CoA can enter the TCA cycle to be
metabolized. However, cannot
enter the TCA cycle directly
Acetyl CoA can enter the TCA cycle to be
metabolized. However, 3C propionyl CoA cannot
enter the TCA cycle directly
45Triglycerides that are formed in the liver are packaged with proteins to form , which are then transported into . Once inside the adipose tissue triglycerides are released from .
Triglycerides that are formed in the liver are packaged with proteins to form VLDL, which are then transported into adipose tissue. Once inside the adipose tissue triglycerides are released from VLDL and stored.
46When the energy requirements are high, the adipose-stored triglycerides are into and
When the energy requirements are high, the adipose-stored triglycerides are hydrolyzed (by the hormone-sensitive lipase) into free fatty acids and glycerol
47Free fatty acids are
oxidized e.g. thru
(b-oxidation) to produce
, , and
Free fatty acids are
oxidized e.g. thru
(b-oxidation) to produce
NADH, FADH 2, and acetyl
CoA.
48The released fatty acids bind to
and send to the
liver for .
The released fatty acids bind to
serum albumin and send to the
liver for fatty acid oxidation.
49Pancreatic lipase (the enzyme that is involved in fat digestion) as part of food digestion is inhibited by the pharmacological compound
Pancreatic lipase (the enzyme that is involved in fat digestion) as part of food digestion is inhibited by the pharmacological compound orlistat.
50Fatty acids must be transported from the into the where the
actual degradation occurs
Fatty acids must be transported from the cytosol into the mitochondrial matrix where the
actual degradation occurs
51Fatty acids can be and for transport
Fatty acids can be activated and converted into fatty acyl carinitine for transport
52How are free fatty acids activated?
-AMP is converted to 2 ADP using adenylate kinase
53Activating fatty acid into fatty acid COA requires to be consumed.
Activating fatty acid into fatty acid COA requires 2 moles of ATP to be consumed.
54The fatty acyl CoA from the cytosol is converted into a
transportable derivative called
catalyzed by the enzyme
The fatty acyl CoA from the cytosol is converted into a
transportable derivative called fatty acyl-carnitine
catalyzed by the enzyme carnitine acyltransferase I.
55Fatty acyl-carnitine enters the mitochondria through a specific carrier system into
the mitochondrial matrix, where it gets converted back to catalyzed by the enzyme .
Fatty acyl-carnitine enters the mitochondria through a specific carrier system into
the mitochondrial matrix, where it gets converted back to fatty
acyl CoA catalyzed by the enzyme carnitine acyltransferase II (CPT II).
56People with carnitine or carnitine palmitoyltransferase (CPT) deficiency are unable to
like palmitic acid.
People with carnitine or carnitine palmitoyltransferase (CPT) deficiency are unable to
metabolize long-chain fatty acids like palmitic acid.
57In adults with a carinitive palitoyltransferase deficiency, what is the most common effect? Newborn?
Adults - muscle weakness, hypoketosis
Neonates - Irregular heart beat
58Where do the NADH and FADH2 produced by b-oxidation go?
The electron transport
system directly to yield energy currency ATP.
59Where does the acteyl CoA produced by b-oxidation go?
Enters TCA cycle and further produces NADH and FADH
60What are the 4 steps of B oxidation?
1.
2.
3. (using )
4. , using
What are the 4 steps of B oxidation?
1. Dehydrogenation
2. Hydration
3. dehydrogenation (using NAD+)
4. Cleavage by a thiolase, using COA
61Each cycle of beta oxidation produces what?
1 molecule each of , , and
Each cycle of beta oxidation produces what?
1 molecule each of FADH2, NADH, and acetyl CoA.
62Each NADH through the electron transport system produces
molecules of ATP and FADH2 produces moles of ATP
Each NADH through the electron transport system produces 3
molecules of ATP and FADH2 produces 2 moles of ATP
63What is the total energy yeild of palmitate?
7 FADH2 (each provide 2 ATP) = 14 ATP
7 NADH (each provide 3 ATP) = 21 ATP
8 Acetyl CoA (each provide 12 ATP) = 96 ATP
TOTAL ATP= 131
NET Yield= 129
64Free fatty acid must be converted to
before it undergoes B-oxidation.
Free fatty acid must be converted to fatty acyl CoA
before it undergoes B-oxidation.
65Fatty acid activation to fatty acyl CoA , therefore deducting that, the net ATP yield is
( ).
Fatty acid activation to fatty acyl CoA consumes 2
ATP, therefore deducting that, the net ATP yield is
(131-2=129 ATP).
66Acetyl CoA can enter the TCA cycle to be
metabolized. However, cannot
enter the TCA cycle directly
Acetyl CoA can enter the TCA cycle to be
metabolized. However, 3C propionyl CoA cannot
enter the TCA cycle directly
67What are the 3 steps of propinonyl coA metabolism?
1. through TCA cycle is converted to
2. Process produces , , and
3. One mole of succinyl coa is moles ATP ( because of step)
What are the 3 steps of propinonyl coA metabolism?
1. Succinyl COA through TCA cycle is converted to oxaloacetate
2. Process produces 1 GTP, 1 FADH2, and 1 NADH
3. One mole of succinyl coa is 6 gross moles ATP (5 net because of propinoyl carboxylase step)