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Oxidation of Fatty Acids: Ketogenesis & Chapter 23:
Biosynthesis of Fatty acids and Eicosanoids )


DATE: 11/23/2010

There is a relationship between intake of carbohydrates  If the cells need energy, pyruvate will be brought
and lipid synthesis. Predominating hormone during inside the mitochondrial matrix and be oxidatively
sembreak (eat, sleep, rest) is insulin. decarboxylated to form Acetyl CoA.

Glucose derived from carbohydrates undergoes glycolysis  β- oxidation

and is stimulated in the presence of insulin. There are o Process whereby cells try to degrade fatty
enzymes that are induced* with the presence of insulin.
o Beta because beta carbon (or carbon
Insulin also stimulates fatty acid synthesis. That is the time number 3) is the one involved
when our cells have the luxury of synthesizing fatty acids  Beta carbon is transformed into a
and there by storing them as triacylglycerol. Triacylglycerol carbonyl carbon (carbon attached
is a molecule with glycerol backbones, and in the carbons to oxygen with a double bond)
of this glycerol are esterified fatty acids.  First 3 steps utilized by
the cells in order to
liberate 2 carbon
moieties from fatty acids
 For cells to degrade fatty
acids, 2 carbons should
be removed at a time
 General Types of pathways:
o Linear pathway
 Glycolysis
 Glucose  Pyruvate (or
lactate in a different case)
o Cyclic pathway
 Kreb’s cycle
 Every turn gives rise to
* Induced/ induction involves 2 processes: transcription and translation. o Spiral pathway
Wherein in enzymes that are critical for stimulation of glycolysis will be  Fatty acid synthesis
synthesized in more amounts such as Fructose 1,6-Bisphosphate and
 β- oxidation of fatty acid
Pyruvate kinase.

** Fatty acid #1 is usually palmitate, Fatty acid #2 is usually oleate, Fatty

acid #3 is oleate or a polyunsaturated fatty acyl group. Every time a cell removes 2 carbon at a time, the cell
utilizes 4 reactions.

 Synthesis of fatty acids is the exact opposite of

I. FATTY ACID SYNTHESIS: how the cells break them down.

 Needs activated intermediates that are bound to a Franz Knoop elucidated the different steps initially making
particular molecule, example of the molecule of up the β- oxidation or the breakdown of fatty acids. And
which activate intermediates are bound is: since the breakdown of fatty acids is in spiral pathway, he
o ACP – Acyl Carrier Protein hypothesized that synthesis of these is exactly in the
 Needs a source of electrons and protons opposite way. And later on he was proven right.
o NADPH + H coming from hexose
monophosphate (alternative carbohydrate Requirements of Fatty Acid Synthesis:
metabolic pathway) pathway and can also
come from citrate shuttle system (aka  Acetyl CoA
Acetyl-CoA shuttle system) o Carbohydrates in the form of glucose after
 Found in the cytoplasm, enzymes that will carry the being transformed to pyruvate enters the
different steps are coming from the cytosol. mitochondrial matrix to be oxidatively
 To carry on the elongation of carbons to make up decarboxylated to form Acetyl CoA
the fatty acid, specifically the palmitic acid, we o The one initially utilized to synthesize fatty
need an enzyme complex known as Fatty Acid acids
Synthase Enzyme Complex. o Acted upon by an enzyme called Acetyl
 After intake a lot of carbohydrates, this will go CoA Carboxylase or ACC enzyme
through glycolysis producing the pyruvate.  Catalyzes the carboxylation
reaction producing Malonyl CoA

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 Catalyzes the rate limiting step for o We start of Acetyl CoA and we elongate
synthesis fatty acids that by utilizing 4 different reactions
 Single, multifunctional enzyme utilized by the cell every cycle (every time
 Requires a biotin group which is a cell adds 2 Carbon Moiety to Acetyl CoA):
attached to a lysine residue of a  Condensation
protein molecule  1st Reduction
 Contains an allosteric regulatory  Dehydration
site  2nd Reduction
 Citrate – most important  Answer:
regulatory factor o 7 cycles or spirals needed
 Catalyzes the rate-limiting step for  We have an original 2 carbon
fatty acid synthesis which forms moiety from Acetyl CoA and cells
malonyl CoA try to elongate this by adding 2
 Long chain fatty acyl CoAse carbons at a time (1 spiral/cycle).
 Inhibits Acetyl CoA So initially 2 carbon moiety plus 2
Carboxylase carbons added per cycle (7 cycles)
o Initial building block is equal to 16 carbons which is
o 2-carbon moiety the number of carbon of palmitic
o 16th and 15th carbon of palmitic acid acid. 2 + (2 x 7) = 16
(most common fatty acid synthesized by
the cell) came from Acetyl CoA and the
rest came from malonyl CoA Question: How many NADPH + H will the cells need to be
 CO2 in the form of bicarbonate able to synthesize a 16-carbon saturated fatty acid?
o Source of carbon
 ATP  Answer: If the cell utilizes 7 cycles, and each of this
o Source of energy to form a covalent bond cycle involves 2 reduction reactions, it needs 14
 Biotin from biocytin NADPH + H because each reduction reaction
o Being a carboxylation reaction wherein the needs one NADPH + H.
the source of carbon is CO2, it is the  For every cycle, we need 2 NADPH+H because we
coenzyme needed by Acetyl CoA have 2 reduction reactions
 Malonyl CoA Malonyl CoA
o Utilized by the cell to lengthen the carbons
from Acetyl CoA  Has 3 carbons
o As a result of carboxylation reaction, it is  Source of 2 carbons used to elongate Acetyl CoA
3-carbon moiety o We only need 2 carbons, and 1 carbon
o It is the source of the 2 carbons used to should be eliminated in the form of
elongate Acetyl CoA Carbon Dioxide.
o In utilizing a 3-carbon moiety, remember  Is taken over by fatty acid synthase enzyme
that the cells only need 2 carbons, so the complex, thereby elongating acetyl CoA to
other one is liberated as CO2 eventually form palmitic acid.
 Signal for the cell to synthesize fatty acids
o It’s a negative allosteric effector for fatty
Question: If the cells will be synthesizing a 16-carbon fatty acid oxidation
acid, how many spirals or cycles will the cells need in order  Cells are endowed with a lot of
to form palmitic acid (most common fatty acid synthesized energy and therefore can
by the cell)? synthesize a lot of fatty acids

Structure of Palmitic acid

 Remember:
o Starting material is a 2-carbon moiety,
Acetyl CoA
 16th and 15th carbon of Palmitic
acid came from the initial Acetyl
 The rest came from Malonyl CoA
o Acetyl CoA Carboxylase (ACC) is only
initially needed to synthesize Malonyl CoA
 After the cells have acted upon
the initial Acetyl CoA by means of
Acetyl CoA Carboxylase, forming
Malonyl CoA. Then the fatty acid
synthase enzyme complex will
now take over the process of Fatty acid Synthase complex
o Fatty acid synthesis is a spiral pathway.  A dimer
o Arranged in a head-to-tail manner

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 A large molecule 3-OHACYL dehydrase Alpha beta trans- Dehydration
 Multiple domain butenoyl ACP

Enoyl Reductase Butyryl ACP 2nd Reduction



7ADP + 7Pi

We need 8 Acetyl CoA molecules, and then from it, we

synthesize 7 Malonyl CoA), 7 ATP, 14 NADPH+H forming
palmitate, releasing 14 oxidized form of NADP, CoA, water,
and 7 ADP and 7 inogrganic phosphates.

It being a dimmer, they are arranged into a head to tail

manner. These subunits carry on the different 4 reactions CITRATE
that are utilized by the cell every cycle of the pathway.
 During starvation (glucagon and epinephrine are
 Transacylation reaction predominating hormones), if the cells need more
 Initial reaction that attaches and activates energy, Acetyl CoA will be shuttled to kreb’s cycle,
intermediates for fatty acid synthesis to ACP and will be condensed with OAA, catalyzed by
(Acyl Carrier Protein). citrate synthase to form citrate.
 Acetyl transacylase  If the cells are endowed with a lot of energy after a
o Enzyme that catalyzes the binding of lot of carbohydrate intake, we will be bombarding
acetyl CoA to the ACP the citric acid cycle with a lot of citrate which
 Malonyl transacylase cannot be accommodated by the next step
o Enzyme that catalyzes the binding of (aconitase and isocitrate dehydrogenase step), so
malonyl CoA to the ACP excess of citrate will go out into the cytoplasm
 Coenzyme A (Citrate Shuttle System)
o Counterpart of Fatty Acid Synthase in

2 reductions and therefore require NADPH+

Needs 7 cycles, 7 malonyl therefore, 14 NADPH+H Inner mitochondrial membrane is highly selective. It would
not allow just the entry and exit of molecules. In the
Enzymes that catalyzes the 4 different reactions: cytoplasm, there will be occurrence of glycolysis to form a
lot of pyruvate. Pyruvate goes into the matrix through
Enzyme Product Reaction pyruvate translocase situated in the inner membrane.
catalyzed Pyruvate in the mitochondrial matrix will then be oxidatively
decarboxylated by pyruvate dehydrogenase (enzyme
3-Ketoacyl ACP Acetoacetyl ACP Condensation
complex) to become acetyl CoA. Acetyl CoA will condense
with oxaloacetate to form citrate with the help of citrate
3-Ketoacyl ACP 3-OH Butyryl ACP 1st Reduction synthase. If there is a lot of energy, excess of citrate will go
reductase out of the cytoplasm and will be converted back to acetyl-

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coA and oxaloacetate with the help of ATP dependent structures. For them to be able to transmit their message
citrate lyase enzyme. Acetyl CoA will be acted upon by inside the cell, they must possess their receptors
Acetyl CoA carboxylase to form malonyl-CoA and thereby expressed on the membrane. Epinephrine (amine hormone)
will be taken over by fatty acid synthase to form fatty acids is derived from tyrosine. The receptor in the plasma
(such as palmitate). Oxaloacetate will be subsequently membrane, epinephrine and glucagon have to bind to the
reduced by malate dehydrogenase cytosolic with the help receptor, forming a hormone-receptor complex to activate
of NADH to form malate. Malate can either go again inside the G-protein. Activated G-protein then activates AC
the mitochondrial matrix or it can be oxidatively (Adenylyl cyclase), that tries to cyclycize ATP to form the 2nd
decarboxylated by malate enzyme (or NADP-dependent messenger, which is cAMP (Cyclic AMP). cAMP activates
malate dehydrogenase enzyme) with the help of NADP, the inactive protein kinase A. If there is an activated
which after oxidizing malate back to pyruvate, the cells protein kinase A, proteins and enzymes will receive
generate NADPH+H (much needed reducing equivalent phosphate groups. Therefore, these enzymes and proteins
needed for fatty acid synthesis). are inactivated due to their phosphorylation.

Therefore, if we will try to count the number of citrate There is a predominance of epinephrine and glucagon
molecules that goes out into the cytoplasm, creating acetyl during starvation. Insulin is exerting the opposite effect of
CoA molecules that the cells utilize for fatty acid synthesis, glucagon. Insulin is also a peptide hormone, which has a
How many of this will be generated, that will contribute to receptor on the membrane. The receptor of insulin is called
the 14 NADPH+H to complete the synthesis of palmitic receptor tyrosine kinase. So from this moment, when it
acid ? binds, after forming a hormone-receptor complex, one of
the actions is to stimulate an enzyme called
 NADPH+H = 14 phosphodiestarase (3’,5’-cyclic AMP phosphodiesterase) to
transform cAMP to 5’-AMP. Therefore, protein kinase is not
 Acetyl CoA needed by the cell to synthesize activated… Enzymes will be in the dephosphorylated form.
palmitic acid = 8 Activated form of Acetyl CoA carboxylase is in
dephosphorylated form, therefore can do its job to
 Citrate = 8 (because from 8 citrates, 8 acetyl CoA
transform Acetyl CoA into Malonyl CoA. But with the
will be formed by citrate lyase enzyme)
predominance of glucagon and epinephrine, Acetyl CoA is
 OAA= 8 converted to pyruvate  (8 NADPH+H is inhibited.
Remember: Enzymes catalyze a specific reactions and
***14 NADPH+H – 8 NADPH+H = remaining 6 NADPH+H therefore specific names:
Protein kinase A  activation is dependent on cAMP.
(which can be provided by HMP or Hexose Monophosphate Protein kinase G  activation is dependent cGMP (a second messenger
Pathway) that activates protein kinase G)
Protein kinase C  activation is dependent on calcium ions (C2+)
As long as we have citrate in the cytoplasm, Acetyl CoA
Carboxylase is stimulated. Covalent modification:

Inactive form Acetyl CoA carboxylase is in the form of  Attachment of phosphate group to enzymes and
monomers. If there are 40 monomers, they try to aggregate proteins
to form the active form (protein-protein interaction).  One way of which the cells try to stimulate/ inhibit
2 opposing pathways
o Ex: Glycogenolysis & Glycogenesis
(Carbohydrate metabolism)
 By attaching a phosphate through glucagon
 Glucagon and epinephrine  1st messengers (they
can transmit messages inside the cells through
cAMP dependent protein kinase A cascade).
Through covalent modifications whereby activity of
most enzymes are activated, while some are
o So.. Depende sa enzymes.. Merong ibang
enzymes na pag naka-tanggap ng
phosphate group, ma-aactivate, meron
naman iba na ma-iinhibit.
 Sa ACC, gumagana lang siya
kapag dephosphorylated sila. So
dapat walang phosphate group.
o Our cells do not have the luxury to
synthesize molecules when there’s a need
for energy. When there is a need for
There is insulin predominance during FA synthesis. The energy, cells mostly induce catabolism to
confirmation of Acetyl CoA carboxylase is in the release a lot of electrons and protons to
dephosphorylated form (activated form). Insulin and be harnessed in ETC. After being carried
by coenzymes such as FAD and NADH+H.
glucagon are peptide hormones, so they cannot just
If we transfer electrons and protons
traverse the plasma membrane due to the nature of the through NADH+H, it will create a PO ratio

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of 3:1 (3 moles of ATP per 1 mole of NADH and series 3 leukotrienes). Furthermore, through a
+ H) and ½ of oxygen molecule (O2) or 1 desaturase delta 5, there will be an introduction of double
oxygen atom will be used as electron bonds in between carbons 5 and 6 to form arachidonic acid
acceptor to form metabolic H2O. If FADH2
(precursor of series 2 prostaglandins and series 4
(2:1), 2 moles of ATP as against 1 atom of
oxygen that serves as the final electron leukotrienes). This can also be elongated after elongation
acceptor to form metabolic water. desaturation to form another precursor for eicosanoid
 The opposite is brought about by the synthesis called tinodonic acid or eicosapentaenoic acid
predominance of insulin  removal of phosphate (precursor of series 3 prostaglandins or series 5
group leukotrienes)
o Wherein it stimulates phosphodiesterase
not adenylyl cyclase
o Insulin also stimulates phosphatase
 Phosphatase removes phosphate dihomo-gamma-linolenic acid 

Therefore, this will now effect attachment of a phosphate,

enzymes in the cytoplasm when interact with protein kinase
A, are activated while some are inhibited.

Introduce a double bond, and elongate the FA to form a

C18, C20, C22 FA.

For introduction of double bond in a saturated fatty acid, we

need a source of electrons and protons coming form
NADH+H with the help of cytochrome B5 reductase, in the Concept of elongation:
participation of FAD. NADH+H transfers electrons to FAD
become reduced to FADH2, that again will be oxidized. Introducing a double bond (action of desaturase) and
FADH2 will transfer electrons and protons to the ferric form adding a carbon atom (elongase) alternately. So initially
(Fe3+) that will be reduced to ferrous (Fe2+) forming a desaturation, elongation, desaturation, and so on.
double bond, with water molecule removal. After
introduction of double bond, elongation process is started.
the predominance of INSULIN.
LINOLEIC ACID: 18 carbon with 2 double bonds situated in
carbon 9 and 10, and carbons 12 and 13. Initially, there
will be an introduction of another double bond between
carbons 6 and 7.

Remember: Polyunsaturated fatty acids have 2 or more double bonds, but

after desaturase activity, it will become 3, 6, 9, 12.

Then there will be an elongation process wherein there is

addition of 2 carbon moiety through elongase enzyme to
form a 20-carbon  dihomo-gamma-linolenic acid or
eicosatrienoic acid (precursor of series 1 prostaglandins

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a. Major carrier of free fatty acids in blood

b. Binds ~6 molecules of fatty acids per 1

molecule of albumin

c. Also binds and transports bilirubin, other

organic anions, and a variety of xenobiotic
compounds (aspirin, barbiturates,
Coumadin, oral hypoglycaemic agents)

In β- oxidation, Malonyl CoA inhibits carnitine acyl
transferase 1 (enzyme needed for beta oxidation) a. Carriers of esterified fatty acids, primarily
as triaglycerols

 Induces glycolysis, therefore forms a lot of pyruvate,

a lot of Acetyl CoA, a lot of citrate which cannot be
accommodated by kreb’s cycle and goes out to the
cytoplasm and is cleaved into acetyl CoA and OAA.
Acetyl CoA will be acted upon by acetyl CoA
carboxylase. More citrate will further stimulate
allosterically your acetyl CoA carboxylase activity,
thereby forming palmitate. When it is activated,
and bound to molecule, forms palmitoyl CoA. From
malonyl to palmitate, we will see the action of fatty
acid synthase complex (FAS).


Lipoproteins, specifically chylomicrons which carry dietary

triacylglycerol, while VLDL carries the endogenously
synthesized triacylglycerol into the circulation.


Epinephrine, glucagon  deactive Protein Kinase A will be

formed and acetyl CoA carboxylase will be phosphorylated
then transforming it into its inactive form. In times of
starvation, we need a lot of energy, and there must be
mobilization of stored triacylglycerol. In the presence of
glucagon and epinephrine, through cAMP dependent
protein kinase cascade, there will be phosphorylation of
hormone-sensitive lipase (sensitive to glucagon and
epinephrine). So now, these hormone sensitive lipase being
Lingual lipase  initial digestion of lipids in the mouth
phosphorylated, thereby activated, will now try to hydrolyze
triacylglycerol into fatty acids and eventually into glycerol Chyme goes down into duodenum and stimulates the
backbone. Fatty acids will be carried into circulation. And in secretion of pancreatic juice. Chyme contains
the circulation, will be carried by albumin protein. 6 lipids/triacyglycerol, proteins, carbohydrates so there is a
molecules of fatty acids in 1 albumin, going back to the variety of enzymes that permits digestion. In this lecture,
liver and is subjected to Beta-oxidation.
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we will focus on the enzyme, PANCREATIC LIPASE since it is ii. Hydrolysis of
the one responsible for lipid digestion. pyrophosphate to 2
inorganic phosphates
Pancreatic lipase acts on dietary triacylglycerols which ensures the
permits the release 2 free fatty acids and a 2- completion of the
monoacylglycerol (there is still a fatty acid esterified at 2nd
Acyl CoA Synthetase
carbon of glycerol backbone). Pancreatic lipase is stabilized
by colipase. Before the action of pancreatic lipase, there is  Also known as thiokinase
an initial step in which the cells have a way to decerase the  Catalyzes the activation of acyl groups, forming
lipid-water interphase so that the hydrophilic enzymes can acyl CoA
interact with hydrophobic triacyglycerols (lipid droplets),  Ex: Palmitic acid + Coenzyme A  Palmitoyl CoA
which we call emulsification. After that, pancreatic lipase o Can now be allowed to enter the matrix.
takes effect. o Acted upon by Carnitine-Palmitoyl
transferase 1
Upon the breakdown, the fates of short and medium chain
fatty acids will be immediately transported into the
circulation, and will undergo oxidation in the mitochondrion
of the liver cells. While long chain fatty acids together with
2-monoacylglycerols (after absorption by intestinal cells),
they will resynthesize triacylglycerol inside intestinal cell
and will be given a coat of apoliprotein B48 to form
chylomicrons and to which the chylomicrons transport them
to the lymphatic system and will eventually be emptied into
the thoracic duct and then to subclavian vein.
Fransup  said that FA must be degraded by removal of 2 Allows the transfer of acyl group to carnitine to form acyl
carbons at a time, which occurs in mitochondrion (by carnitine, subsequently releasing coenzyme A. As acyl
Leninger). And 2 carbons released is not acetate, but carnitine, it can now be translocated inside the matrix
acetyl-CoA (FA synthesis is also called as Linen Cycle) through the help of a protein embedded in the inner
mitochondrial membrane, which is named as carnitine-acyl
BETA-OXIDATION OF FATTY ACIDS carnitine translocase. Inside the matrix, this acyl carnitine
will be subsequently acted upon by carnitine-palmitoyl
 Beta carbon is the one involved in the process of transferase 2, transferring acyl group back to Coenzyme A,
cleavage releasing carnitine. Carnitine will be translocated outside
i. By transforming this 3rd carbon into into the intermembranous space, by means of the
carbonyl/carboxyl carbon translocase, in time for the second load of palmitoyl-Coa
ii. Done by the 1st 3 steps exactly opposite of
the Fatty Acid synthesis (Condensation,
**Carnitine-Acyl Transferase 1 is just a general name, while Carnitine-
Reduction, Dehydration)
Palmitoyl Transferase 1 is a more specific one.
1. Oxidation
2. Hydration
3. 2nd Oxidation
4. Cleavage
 Cells liberate phenylacetate  true for even chain
fatty acids
 Cells liberate benzoic acid  true for odd chain
fatty acids
 Cell degrade fatty acids by removal of 2 carbons at
a time

 For fatty acid oxidation:

i. Molecule attached to intermediate is attached
by Coenzyme A (counterpart of transacylase in
fatty acid synthesis) which is carried out by
Acetyl CoA Synthetase
ii. 2-step reaction
1. ATP is hydrolyzed to AMP +
Pyrophosphate Site of action of malonyl CoA inhibits carnitine-palmitoyl
2. Pi is hydrolyzed by pyrophosphatase transferase 1. Carnitine-palmitoyl transferase 1. Malonyl
to liberate 2 Pi CoA is the rate limiting for beta-oxidation.
a. Energy liberated by 1 mole of
Pyrophosphate being Carnitine is a molecule is synthesized by liver and kidney
hydrolyzed to Pi = -6.6 kCal cells from Lysine and Methionine. In the biostatic pathway,
i. If this is the kind of there are 2 enzymes that need the coenzyme vitamin,
hydrolysis carried out, ascorbic acid.
it amounts to 2 moles
of ATP Different steps repeated every cycle in the pathway of B-
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the mitochondrion, palmitate must be activated and
therefore must be attached to coenzyme A through acyl
CoA synthetase. And in the process, it utilizes 2 moles of
ATP. Therefore if we would like to know the net amount of
ATP produced, we have to subtract 2 moles of ATP to know
the net amount of ATP is 129 moles per 1 mole of palmitic

For additional information:

In the 1st step: OXIDATION:

 1.5~ 2 ATP is the original amount for FADH2

 2.5~ 3 ATP is the original amount for NADH+H


 Can also be utilized and can be subjected to

normal B-oxidation
 15-carbon FA  beta-oxidation removes up to the
12th carbon. The last 3 corresponds to carbon
Oxidation carried out by Acyl CoA dehydrogenase with the number 1, alpha carbon (2nd carbon), and beta
help of FAD (the one that will receive protons and electrons), carbon (3rd carbon). The resulting 3-carbon moiety
which is subsequently reduced to FADH2. FAD can easily in the form of Propionyl CoA can still be utilized by
the cell to generate energy.
transfer to ETC, creating a PO ration of 2:1. After the 1st
oxidation, the product is trans delta 2 Fatty enoyl CoA.
Through hydration, the double bond is hydrated and there
is formation of L-beta-Hydroxy acyl CoA with the help of
enoyl CoA hydratase and a water molecule. After hydration
reaction, comes the second oxidation with the help of NAD
with the help carried out by L-hydroxy acyl CoA
dehydrogenase, forming NADH+H which goes to electron
transport chain, creating a PO ratio of 3:1. Finally, the beta-
carbon becomes the carbonyl carbon. With the help of
Coenzyme A, the sulfur atom in it carries a lone pair of
electrons. Oxygen is more electron negative than carbon, so
it is a neutrophile that attracts electron to itself, which
makes carbon more positive. If we have there a nucleophile,
it can easily attack there through a nucleophilic attack,
cleaving the bond and releasing acetyl CoA, shortening
original FA by 2 carbons and the cycle will go on. If FA is
palmitic acid, there is 7 cycles, therefore yields 1 mole of
FADH2 and 1 mole of NADH+H per cycle, 5 ATP generated
per cycle (because this will create 2(from FADH2 +3 from
NADH + H). How many moles of acetyl CoA from B-
oxidation of palmitic acid? 8 moles of Acetyl CoA. How
many moles of ATP?
Propionyl CoA is carboxylated through propionyl CoA to form
How many FADH2? = 7 D-Methylmalonyl CoA and this will be isomerized by
epimerase to form L-Methyl Malonyl CoA and through
How many NADH+H = 7
methylmalonyl CoA mutase, forms succinyl CoA.
8 Acetyl CoA goes to the TCA cycle to synthesize more
Succinyl CoA is an intermediate of Kreb’s cycle. With this
energy during starvation. Remember that 1 mole of Acetyl
respect, form L-Methylmalonyl CoA to be catalyzed by
CoA, when enters the TCA cycle yields 12 ATPs.
mutase to form Succinyl CoA. Mutase is one of the 2
Gross amount of ATP generated out of complete beta- enzymes in which vitamin B12 (in the form of 5-
oxidation of palmitic acid is (12ATP x 8) + 14 ATP + 21 ATP deoxyadenosyl cobalamine) is needed. While the other
= 131 gross ATP per mole of palmitic acid enzyme that needs vitamin B12 is methionine synthase
enzyme which catalyzes the synthesis of methionine from
2 moles of ATP utilized in acyl CoA synthetase to activate FA homocystein. This methionine synthase needs vitamin B12
to form palmitoyl CoA. Palmitic acid that will be oxidized (in the form of Methyl Cobalamine).
through Beta-oxidation came from the deposited
triacylglycerol through the action of HSL (Hormone UNSATURATED FATTY ACIDS
Sensitive Lipase). Palmitate is carried by albumin in the
circulation to bring it back to the liver. Before it enters to  Cells can also utilize them for energy purposes.

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 2 kinds of unsaturated fatty acids:

1. Monounsaturated Fatty Acids

Carbon number 1, Carbon number 2 (alpha carbon), Carbon number 3

(beta carbon) has a methyl substituent; our cells do not have an enzyme
to act upon the beta carbon with a methyl substituent. The cells then
utilize alpha oxidation, wherein the alpha carbon will be the carbonyl
carbon, and the carbon number 1 is liberated as CO2. When carbon 1 is
removed, the former alpha carbon becomes the carbon number 1, and
the former beta carbon will not have branch. So therefore, this can be
subjected to the 4 steps that are repeated every cycle of the pathway.

If that is the case, the cleavage will be at the site wherein it releases
propionyl CoA (a 3-carbon moiety). Propionyl CoA is transformed to
Succinyl CoA and eventually enters Kreb’s cycle. Beta carbon can be
  subjected to a normal beta oxidation, releasing Acetyl CoA (2-carbon
moiety). After that, it releases propionyl CoA again.
Initially, there is a double bond situated in carbon 9 and 
10. Initially, oleoyl CoA is subjected to 3 cycles of normal 
B‐oxidation. After removing 6 carbons, the initial carbon  Refsun’s Disease refers to the accumulation of phytanic
7 becomes carbon 1, carbon 8 now becomes our alpha  acid especially in the brain, secondary to enzyme
carbon, and carbon 9 becomes the beta carbon. The beta 
carbon as we can see is now involved in a double bond, 
which our cells will not be able to utilize the carbon with 
double bond. So the cells isomerizes  cis‐delta‐3‐ OMEGA OXIDATION
Dodecenoyl CoA forming trans‐delta‐2‐Dodecenoyl CoA, 
which can be subsequently hydrated with a mole of   Last carbon or the omega carbon is transformed
water to form L‐beta‐Hydroxy‐Decanoyl. After this we  into a carboxylic carbon.
can now utilize the normal B‐oxidation cycle to degrade 
this kind of fatty acid.
o If this happens, both sides can be
subjected to normal B-oxidation
2. Polyunsaturated Fatty Acids

2 double bonds are seen between carbons

9 and 10, 12 and 13 and they undergo 3
cycles of beta-oxidation. Afterwhich, the
beta carbon is again involved in a cis
confirmation of double bond. By means of
an isomerase, it can be transformed into a
trans-delta-2-enoyl CoA.

Cells use isomerase initially, then

dehydrogenase, and lastly reductase so
that normal B-oxidation of polyunsaturated
fatty acids may be take place. SHORT TERM REGULATION FOR FA METABOLISM:


 Flavin-dependent reaction
 Amount of energy in the form of ATP is less
because electrons are not transformed to ETC, but
instead transferred to a molecular oxygen, forming
hydrogen peroxide
 Hydrogen peroxide is a harmful compound that is
degraded to oxygen and water by the catalase


 Oxidizes branched chain fatty acids

 We derive metabolite intermediate coming from  Glucagon and Epinephrine phosphorylate the
chlorophyll (phytanic acid), a branched chain of acetyl CoA carboxylase, which forms cAMP which
fatty acid. then activates protein kinase A and therefore
 May also be a source of energy. phosphorylates, ACC, inhibiting its activity.

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o So instead of FA synthesis, the  Acetone + dehydrogenase
predominant pathway is beta-oxidation,
forming a lot of acetyl Coa. Acetyl CoA Liver is the site of ketogenesis. But with respect to energy
goes to kreb’s cycle. utilization, the liver cannot utlize them as source of energy
due to the absence of succinyl CoA -aceto-acetate CoA
transferase (thiophorase). “Ako ang nag saing, iba ang kumain.
Awww Emo much:(”


 Autocrine (the same cell that secretes the

hormone will be the one affected) and paracrine
hormones (adjacent cells will be the ones that will
be affected).
 Example: Prostaglandins, leukotrienes,
thromboxanes, lipoxins
 Synthesized from
o 20-carbon FA (AKA eicosanoic acids)
 Arachindonic (4 double bonds) 
series 2 prostaglandins (through
cycleoxygenase pathway)
 Timnodonate (5 double bonds)
 Eicosapentaenoic acids  series
3 prostaglandins
After oxidation, cells form a lot of ketone bodies. And if cell  Eicosatrienoate
is in starvation, the source of energy is from Acetyl CoA
then the cell forms a lot of ketone bodies. Condensation of
Exert their effects through formation of cAMP.
2 moles of Acetyl CoA catalyzed by thiolase, with the
release of coenzyme A forming acetoacetyl CoA. By means
 They have to bind to the receptor in the plasma
by synthetase and with another mole of Acetyl CoA, we will membrane which stimulates the G-protein which
form 3-hydroxy-3-methylbutaryl CoA, with the release of activates Adenylyl Cyclase, which forms cAMP out
acetyl CoA, we form the 1st ketone body—acetoacetate. of ATP (cAMP protein dependent kinase cascade).

Acetoacetate forms acetone.

Physiological responses:

 Negates inflammatory responses

 Produce pain and fever
 Regulate blood clotting
 Induce labor (for specific kinds)
 Have an effect on regulation of split weight cycle
 Inhibits gastric secretions
 Stimulate contraction of intestinal smooth muscles


 Identified in human semen and other cells

 Prostaglandin E and Prostaglandin F are initially
 Derived from hypothetical prostanoic acid
 There are 3 major classes (depending on the
Acetone structure):
o Prostaglandin A – α,β- unsaturated
 A volatile ketone body which is released through ketones
respiration. o Prostaglandin E- β- hydroxy ketones
o Prostaglandin F- 1,3 dioles (2 hydroxy
 Its accumulation may also result to type 1 diabetes groups)
mellitus which has the propensity to develop Series 1 prostagalinds– there is 1 double bond outside the
ketoacidosis due to the absence of insulin cyclicized region from eicosatrienoic acid or dihomo-
synthesis. gamma-linolenic acid

3-hydroxy Butarate Series 2 prostaglandins – there are 2 double bonds outside

the cyclicized region from eicosatetraenoic acid or
 Another ketone body arachidonic acid

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Series 3 prostaglandins – there are 3 double bonds outside o Cyclooxygenase activity is inhibited by
the cyclicized region from eicosapentaenoic acid or aspirin (acetylsalicylic acid) and ibuprofen
timnodonic acid (Non-steroidal anti-inflammatory drugs)
 2 isoforms of cyclooxygenase
Among the unsaturated fatty acids, there are 2 essential  COX1 – a constitutive
polyunsaturated acids: enzyme (it’s always
present whether or not
1. linoleic acid (true essential) there are substrates)
a. From this, we can synthesize dihomo- o When blocked,
gamm-linolenic through a GI bleeding and
dehydrogenation reaction gastritis
2. linolenic acid o Needed for the
maintenance of
integrity of the
membranes of
intestinal cells

 COX2 – an inducible
o Made only in
initiators such as
o The one that is
o Celecoxib are
o Catalysis through lipooxygenase o Cyclooxygenase activity is inhibited by
o Series 3 from eicosatrienoate aspirin and ibuprofen (Nonsteroidal anti-
o Series 4 from arachidonic acid inflammatory drugs)
o Series 5 from eicosapentaenoate

Pathway for Cyclooxygenase:

Arachidonic acid is the most important precursor.
o Prostaglandin H2 synthase enzyme complex:
o Generation of Arachidonic acid through: o Possesses:
o Reaction of phospholipase A2 which acts  Cyclooxygenase activity
on carbon 2 of glycerol backbone.  Aspirin inhibits this
o Phospholipase A1 acts on carbon 1 of activity
glycerol backbone  Peroxidase activity
o Phospholipase C acts on carbon 3
o Phospholipase D removes the base.
 Ex: Enositol portion of Structure of cyclooxygenase domain has 3 important amino
phosphatidyl enositol is removed acid residues
through this phospholipase D.
o Diacylglycerol lipase 1. Tyrosine 3,8,5
o Diacylglycerol kinase a. Forms a radical in the process of forming
b. If we give NSH, it will affect the tyrosine
Phosphatidyl enositol through phospholipase A2  residue that prevents the formation of
arachidonic acid + lysophospholipid radical
2. Serine 5,30
Diacylglycerol kinase + phospholipase C  phosphatidic a. Aspirin acetylates this, producing acetyl
acid (+ phospholipase A2 arachidonic acid) moiety which blocks the whole entry of
arachidonic acid
Diacylglycerol lipase from 1,2 diacyl glycerol  arachidonic 3. Arginine 1,20
acid a. Forms an ion pair with substrate
b. If arachidonic acid cannot enter, arginine
2 major pathways of arachidonic acid metabolism: cannot forms an ion pair with substrate

1. Cyclooxygenase (Cyclic pathway)

2. Lipooxygenase (Linear pathway) Phospholipase A2 generates arachidonic acid

o Hormones that stimulate angiotensin 2:

Shows us how Arachidonic Acid  Prostaglandin o Bradykinin
o Epinephrine
o Thrombin
o 2 activities:
o Cortisol (principle corticosteroid) inhibits the
activity of phospholipase A2
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o WBC, Muscles, Lungs, Brain
o Actions:
Prostaglandin dehydrogenase  Induces release of lysosomal enzymes
 Promotes adhesion of WBC
o Carbon attached to hydroxyl group is subsequently
oxidized, and therefore inhibits prostaglandin
o Message is transmited by the formation of 2nd
messenger of cAMP


 Family of congregated tetraenes

 Vasoactive and immunoregulatory effects

-----------------------END OF TRANSCRIPTION-------------------------------

Kung hindi clear yung image, please refer to the uploaded

pdf file if it is available

o Peptidoleukotriene – mediates anaphylaxis

o Leukotriene C4
o Leukotriene D4
o Leukotriene E4

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