Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.
What is Lipogenesis?
 It is the metabolic pathway by which fatty acids
are synthesized from Acetyl-CoA.
 It is not simpl...
Some Differences Between Lipogenesis
and β-oxidation pathway
Oxidation Synthesis
Reaction site Mitochondria Cytosol
Enzyme...
THE CITRATE – MALATE SHUTTLE SYSTEM
 The acetyl CoA is the starting material for
lipogenesis.
 Because acetyl CoA is gen...
 The outer mitochondrial matrix is freely
permeable to acetyl CoA, as well as many other
substances such as citrate, mala...
THE CITRATE – MALATE SHUTTLE SYSTEM
THE CITRATE – MALATE SHUTTLE SYSTEM
 Mitochondrial acetyl CoA reacts with
oxaloacetate to produce citrate, which is then
...
 The acetyl CoA so generated becomes the
“fuel” for lipogenesis; the oxaloacetate so
generated reacts further to produce ...
ACP COMPLEX FORMATION
 Two simple ACP complexes are neede to start
the lipogenesis process.
 They are acetyl ACP, a C2–A...
 Cytosolic acetyl CoA is the starting material for the
production of both of these simple ACP complexes.
Acetyl ACP is pr...
 The reaction to produce malonyl, ACP requires
two steps . The first step is a carboxylation
reaction with ATP involvemen...
 This reaction occurs only when cellular ATP levels are high. It is
catalyzed by acetyl CoA carboxylase complex, which re...
THE CHAIN ELONGATION
 Four reactions that occur in a cyclic pattern
within the multienzyme fatty acids synthase
complex c...
Acetyl ACP Malonyl ACP
Crotonyl ACP
Acetoacetyl ACP
Butyryl ACP
β-Hydroxybutyryl ACP
+
1. CONDENSATION
2. HYDROGENATION
3....
STEP 1: CONDENSATION.
Acetyl ACP and malonyl ACP condense together
to form acetoacetyl ACP.
O O O
II II II
CH3—C—S—ACP+ -O...
STEP 2: FIRST HYDROGENATION.
The Keto group of the acetoacetyl complex,
which involves the β-carbon atom, is reduced to
th...
STEP 3. DEHYDRATION
The alcohol produced in STEP 2 is dehydrated
to introduce a double bond into the molecule
(between α a...
STEP 4: SECOND HYDROGENATION
The double bond introduced in step 3 is
converted to a single bond through
hydrogenation. As ...
O
II
CH3—C—S—ACP
Acetyl ACP
O
ll
CH3--(C2)14—C—O-
C16 Fatty acid
O
II
CH3—CH2—CH2—C—S—ACP
C4 Fatty acid
O
Il
CH3—CH2—CH2— ...
BIOSYNTHESIS OF CHOLESTEROL
 The biosynthesis of cholesterol, a C27 molecule
, occurs primarily in the liver.
 Its produ...
Acetyl CoA
C2
Mevalonate
C6
Cholesterol
Multiring
C27
Lanosterol
Multiring
C30
Squalene
Acyclic
C30
Isopentyl
Pyrophosphat...
 In the first phase of cholesterol synthesis, three
molecules of acetyl CoA are condensed into a
C6 mevalonate ion.
The C6 mevalonate undergoes a decarboxylation to yield a C5
isoprene derivative called isopentenyl pyrophosphate and CO2 ....
The next stage of cholesterol biosynthesis
involves the condensation of six isoprene units
to give the C30 squalene molecu...
 The multistep squalene-to-lanosterol transition involves the
formation of four ring systems.
 A decrease in double bond...
 The transition from lanosterol to cholesterol involves
removal of three methyl groups (C30 to C27 ), reduction
of the do...
 Once the cholesterol has been formed,
biosyhthetic pathways are available to convert
it to each of the five major classe...
Cholesterol
C27
Progestins
C21
Mineralocorticoids
C21
Androgens
C19
Glucocorticoids
C21
Estrogens
C18
Biosynthetic Relatio...
THANK YOU… 
TO GOD BE THE GLORY
PREPARED BY:
LEIZEL A. DESPI
BSED 2C
Lipogenesis (Fatty Acid Biosynthesis)
Upcoming SlideShare
Loading in …5
×

Lipogenesis (Fatty Acid Biosynthesis)

21,149 views

Published on

Published in: Education
  • Login to see the comments

Lipogenesis (Fatty Acid Biosynthesis)

  1. 1. What is Lipogenesis?  It is the metabolic pathway by which fatty acids are synthesized from Acetyl-CoA.  It is not simply a reversal of the steps of degradation of fatty acids (the β-oxidation pathway).
  2. 2. Some Differences Between Lipogenesis and β-oxidation pathway Oxidation Synthesis Reaction site Mitochondria Cytosol Enzymes involved (Independent ) Fatty acid synthase Intermediates carrier Coenzyme A Acyl carrier protein Coenzymes FAD, NAD+ NADPH Carbon atoms Removed two at a time Added two at a time
  3. 3. THE CITRATE – MALATE SHUTTLE SYSTEM  The acetyl CoA is the starting material for lipogenesis.  Because acetyl CoA is generated in mitochondria and lipogenesis occurs in the cytosol, the acetyl CoA must be transported to the cytosol.  It exits the mitochondria through a transport sytem that involves citrate ion.
  4. 4.  The outer mitochondrial matrix is freely permeable to acetyl CoA, as well as many other substances such as citrate, malate, and pyruvate.  The inner mitochondrial membrane, however is not permeable to acetyl CoA.
  5. 5. THE CITRATE – MALATE SHUTTLE SYSTEM
  6. 6. THE CITRATE – MALATE SHUTTLE SYSTEM  Mitochondrial acetyl CoA reacts with oxaloacetate to produce citrate, which is then transported through the inner mitochondrial membrane by a citrate transporter.  Once in the cytosol, the citrate undergoes the reverse reaction to its formation to regenerate the acetyl CoA and oxaloacetate, with ATP involved in the process.
  7. 7.  The acetyl CoA so generated becomes the “fuel” for lipogenesis; the oxaloacetate so generated reacts further to produce malate, in an NADH dependent change.  The malate reenters the mitochondrial matrix through a malate transporter, and is then converted to oxaloacetate, which can then react with another acetyl CoA molecule to form citrate and the shuttle process repeats itself.
  8. 8. ACP COMPLEX FORMATION  Two simple ACP complexes are neede to start the lipogenesis process.  They are acetyl ACP, a C2–ACP, and malonyl ACP, a C3 --ACP .  Additional malonyl ACP molecules are needed as the lipogenesis process proceeds.
  9. 9.  Cytosolic acetyl CoA is the starting material for the production of both of these simple ACP complexes. Acetyl ACP is produced by direct reaction of acetyl CoA with and ACP molecule. O acetyl transferase O CH3—C—S—CoA + ACP—S—H CH3—C—S—ACP + CoA—S—H Acetyl CoA Acetyl ACP CoA
  10. 10.  The reaction to produce malonyl, ACP requires two steps . The first step is a carboxylation reaction with ATP involvement. O O O CH3—C—S—CoA + CO2 - 0—C—CH2—C—S--CoA Acetyl CoA ATP ADP + Pi Malonyl CoA
  11. 11.  This reaction occurs only when cellular ATP levels are high. It is catalyzed by acetyl CoA carboxylase complex, which requires both Mn2+ ion and the B vitamin biotin for its activity. The malonyl CoA so produced then reacts with ACP to produce malonyl ACP. o o o o  malonyl transferase - 0—C—CH2—C—S—CoA + ACP—SH - 0—C—CH2—C—S—ACP +CoA—S—H malonyl CoA ACP malonyl ACP CoA
  12. 12. THE CHAIN ELONGATION  Four reactions that occur in a cyclic pattern within the multienzyme fatty acids synthase complex constitute the chain elongation process used for fatty acids.  The reactions of the first turn of the cycle, in general terms
  13. 13. Acetyl ACP Malonyl ACP Crotonyl ACP Acetoacetyl ACP Butyryl ACP β-Hydroxybutyryl ACP + 1. CONDENSATION 2. HYDROGENATION 3. DEHYDRATION 4. HYDROGENATION ACP CO2 NADPH/H+ NADP+ H2O + NADPH/H+ NADP+ CHAIN ELONGATION
  14. 14. STEP 1: CONDENSATION. Acetyl ACP and malonyl ACP condense together to form acetoacetyl ACP. O O O II II II CH3—C—S—ACP+ -O—C—CH2—C—S—ACP O O II II CH3—C—CH2—C—S—ACP + CO2 + ACP—SH Acetyl ACP Malonyl ACP Acetoacetyl ACP
  15. 15. STEP 2: FIRST HYDROGENATION. The Keto group of the acetoacetyl complex, which involves the β-carbon atom, is reduced to the corresponding alcohol by NADPH. O O OH O II II I II CH3—C—CH2—C—S—ACP CH3—CH—CH2—C—S—ACP NADPH/H+ NADP+Acetoacetyl ACP β-Hydroxybutyryl ACP
  16. 16. STEP 3. DEHYDRATION The alcohol produced in STEP 2 is dehydrated to introduce a double bond into the molecule (between α and β carbons.) OH O O l ll ll CH3—CH—CH2—C—S—ACP CH3—CH=CH—C—S—ACP β-Hydroxybutyryl ACP Crotonyl ACPH2O
  17. 17. STEP 4: SECOND HYDROGENATION The double bond introduced in step 3 is converted to a single bond through hydrogenation. As in step 2, NADPH is the reducing agent. o o trans ll ll CH3—CH=CH—C—S—ACP CH3—CH2—CH2—C—S—ACP Crotonyl ACP Butyryl ACP NADPH/H+ NADP+
  18. 18. O II CH3—C—S—ACP Acetyl ACP O ll CH3--(C2)14—C—O- C16 Fatty acid O II CH3—CH2—CH2—C—S—ACP C4 Fatty acid O Il CH3—CH2—CH2— CH2--CH2 C—S—ACP C6 Fatty acid Cycle repeats Malonyl ACP CO2 Malonyl ACP Malonyl ACP Malonyl ACP CO2 CO2 CO2
  19. 19. BIOSYNTHESIS OF CHOLESTEROL  The biosynthesis of cholesterol, a C27 molecule , occurs primarily in the liver.  Its production consumes 18 molecules of acetyl CoA and involves at least 27 separate enzymatic steps.
  20. 20. Acetyl CoA C2 Mevalonate C6 Cholesterol Multiring C27 Lanosterol Multiring C30 Squalene Acyclic C30 Isopentyl Pyrophosphate C5 Several Steps Several Steps Several Steps Several Steps Several Steps OVERVIEW OF THE BIOSYNTHETIC PATHWAY FOR CHOLESTEROL SYNTHESIS
  21. 21.  In the first phase of cholesterol synthesis, three molecules of acetyl CoA are condensed into a C6 mevalonate ion.
  22. 22. The C6 mevalonate undergoes a decarboxylation to yield a C5 isoprene derivative called isopentenyl pyrophosphate and CO2 . Three ATP molecules are needed in accomplishing this process.
  23. 23. The next stage of cholesterol biosynthesis involves the condensation of six isoprene units to give the C30 squalene molecule.
  24. 24.  The multistep squalene-to-lanosterol transition involves the formation of four ring systems.  A decrease in double bonds from six to two.  The migration of two methyl groups to new locations, and the addition of an –OH group to the C30 system.  Addition of the –OH group requires the use of molecular oxygen; the O of the –OH group comes from the molecular O2 . SQUALENE LANOSTEROL
  25. 25.  The transition from lanosterol to cholesterol involves removal of three methyl groups (C30 to C27 ), reduction of the double bond in the side chain, and migration of the other double bond to a new location.
  26. 26.  Once the cholesterol has been formed, biosyhthetic pathways are available to convert it to each of the five major classes of steroid hormones: progestins, androgens, estrogens, glucocorticoids, and mineralocorticoids, as well as to bile acids and vitamin D.
  27. 27. Cholesterol C27 Progestins C21 Mineralocorticoids C21 Androgens C19 Glucocorticoids C21 Estrogens C18 Biosynthetic Relationship among Steroid Hormones
  28. 28. THANK YOU…  TO GOD BE THE GLORY PREPARED BY: LEIZEL A. DESPI BSED 2C

×