Fatty Acid Synthesis Flashcards
Fatty acids are synthesized primarily in the ___
liver.
how to get FA from pyrvuate?
- pyvuvate –> citrate
- citrate leaves mitocondira
3. citrate —> acetyl CoA
- acetyl CoA –> malonyl CoA
- manlonyl CoA is 2C donot for FA synthesis
____ is 2C donot for FA synthesis
manlonyl CoA
what is the product of FA synthesis? what is its structure?
palmitic acid, a sixteen carbon saturated fatty acid.
pyruvate –> Pyruvate dehydrogenase by??
Pyruvate dehydrogenase
pyruvate –> oxaloacetate (OAA) by??
Pyruvate carboxylase
** Pyruvate carboxylase** and Pyruvate dehydrogenase are regulated based on what?
e level of acetyl CoA in the mitochondria
When Acetyl CoA is at high concentration the Pyruvate dehydrogenase is ____
inhibited
When Acetyl CoA is at high concentration the Pyruvate dehydrogenase is inhibited causing —->
an INC Pyruvate carboxylasse —->INC OAA.
The reduction in acetyl CoA leads to
- activation of the dehydrogenase
- inhibition of carboxylase.
What happens with Citrate in the cytosol
cleaved to Acetyl CoA and OAA by _Citrate Lyase. _
in the cytosol, citrate is cleaved to Acetyl CoA and OAA by ___
Citrate Lyase.
Whybreak down citrate in the cytosol too when you have already produced Acetyl CoA and OAA in the mitochondria?
- The Pyruvate dehydrogenase is only found in the mitochondria.
- Acetyl CoA cannot cross the mitochondrial double membrane.
NADPH is required for the ___ of Fatty Acids.
NADPH
NADPH is required for the synthesis of Fatty Acids.
One source of NADPH for synthesis of FA is the recycling of the OAA
what are the two steps?
- OAA is reudced to Malate by NADH dependent maltase dehydrogenase
- Malate converted to NADP-dependend Malix enzyme
- Malic enzyme oxidizes and decboxyltes Malate –> pyruvate
sources of NADPH for FA synthesis (2)
- recycling OAA
- Pentose Phosphate pathway
2 enzymes involved in FA synthesis?
Acetyl CoA Carboxylase and Fatty Acid Synthase
___ enzymes is involved in the rate controlling step of FA synthesis
Acetyl CoA Carboxylase
what rxn does Acetyl CoA Carboxylase catlayze in Fa synthesis?
Acetyl CoA —> Malonyl COA
Acetyl CoA —> Malonyl COA
what is the cofactor ACC binds to?
biotin
Acetyl CoA —> Malonyl COA
waht is consumed? generated?
ATP hydrolysized to ADP + Phosphate
What regulates Acetyl CoA Carboxylase?
- Citrate – causes it to polymerize
- Insulin stim. phopshatase
- Caloric intake/ACC transcription levels
- ** Glucagon/Epinephrine stimulated A-Kinase**
- ** Palmitoyl CoA** levels
- ** AMP** (low energy levels)
5 steps in FA synthesis?
- Activation: carboxylation of acetyl CoA to malonyl CoA
- Condensation: formation of the β -keto group
- Reduction of the β -keto group
- Dehydration of the a, b carbons
- Reduction of the a, b double bond
what are steps 2-5 of FA synthesis catalyzed by?
Fatty Acid Synthase (FAS)
WHat does Fatty Acid Synthase do to MALONYL COA?
takes 2C FROM MALONYL COA, GIVES IT TO GROWING FATTY ACYL CHAIN
each subunit of Fatty Acid Synthase contains (2)
- 7 catalytic activities
- an acyl carrier protein in a single polypeptide chain
Phosphopantetheine is linked to a serine within the ____) portion of fatty acid synthase
acyl carrier protein (ACP)
___ of fatty aci synthase reacts with malonyl COA to form a thioester fond
sulfhydral group
fatty acid synthase
the two subunits associate ____o that the phospho-pantetheinyl sulfhydryl group on one subunit is close to the cysteinyl sulfhydryl group on the other subunit.
head-to-tail s
what is fatty acid synthase derived from?
pantothemnic acid?
condensation step
Malonyl CoA attaches to the ____ part of the ACP of FAS
phosphopantetheinyl (P)
step 2: condensation
after** acetyl group from acetyl Coa** first associates with the ACP phospho-pantetheinyl sulfhydryl group, it is then
transferred to the cysteine sulfhydryl of the other subunit.
after acetyl group from acetyl coa associated with ACP sulfhydryl group. what happens?
Malonyl from malonyl CoA then associates with the ACP phospho-pantetheinyl sulfhydryl group.
step 2: condensation
The acetyl and malonyl groups condense with release of the malonyl carboxyl group as
CO2
step 2: condensation
after coa2 is released by condensation, ___ is created
4C ** β−keto acyl chain** which is attached to the ACP phospho-pantetheinyl sulfhydryl group.
* will eventually become the omega methyl group of palmitate is labelled ω.
step 3:
n Fatty Acid Synthesis include a reduction of the β−keto group to an___
alcohol
step 4
dehydration to form a ____
double bond
step 5
another reduction step reduces the_____
double bond.
in fa synthesis, NADPH provides the reducing equivalents for what steps
step 3 – reduing b-keto group –> alcohol
step 5 – reducing double bound
steps 2-5 are repeated with the result being a ___
6C fatty acyl chain
after stepes 2-5 make 6C fatty acyl chain, the series of reactions is repeated until
he fatty acid chain is 16 carbons
after the he fatty acid chain is 16 carbons then
hydrolysis occurs and palmitate is released.
after palmitiate si reelased from fAS it is activated to
palmitoyl coa
palmityl coa and other long chain fatty acyl coas can be elongated ___ carbons at a time
two
where are fa chains elongated? by what enzymes?
in the er
by elongases
difference between steps in elongation and synrhsis of fa?
the long fatty acid is attached to coenzyme A instead of a phophopanthetinyl residue
Desaturation is the oxidation of fatty acids resulting in
cis double bonds.
____ of FA creates lipids of increasing structural and functional complexity with
distinct biological roles.
Desaturation
what does fa desaturation require? where is it found
desaturases, found in the er
what do desaturases require
o2
nadh
cytochrome b5 (where electrons pass through)
During starvation, desaturase activities
decrease sharply
desaturase ___ upon feeding with carbohydrate.
increases
When large amounts of ____ are eaten desaturase activities decrease.
unsaturated fats
Humans have what three distinct Desaturases distinguished by the position of the double bond insertion within the fatty acid chain.
Ø Δ9 desaturase
Ø Δ6 desaturase
Ø Δ5 desaturase
The most common desaturation reactions involve an
oxidation leading to a double bond between ___
C9 and C10.
what is required for eicosinoid synthesis.
polyunusaturated FAs with double bonds 3 C s(ω3) o r6 carbons (ω6) from the methyl end
We do not synthesize the____ fatty acids de novo so they must come from our diet
ω3 and ω6
linoleic and linolenic fatty acids primarily from plant oils help prodvide
ω3 and ω6 fatty acids, since we do not syntehsis these de novo
importance of arachidonic acid?
- PRECURSOR OF SEVERAL EICOSANOIDS
- IMPORTANT COMPONENT OF MEMBRANE LIPIDS
Linoleic acid can be converted by elongation and desaturation reactions to ___
arachidonic acid
is Arachidonic acid an essential fa?
not if lioleic acid is present since that can syntehsize it
____ is a susbtrate for leukotrienes, thromboxanes, prostaglandins
arachidonic acid
Eicosanoids include the (3)
prostaglandins, thromboxanes and leukotrienes
Eicosanoids tend to be unstable and ahve very __ biological half life
short
what are the three pathways that metabolize arachidonic acid
- via cycloxgenase – forms the prostaglandins, thromboxanes and prostacyclins;
- via lipoxygenase – forms leukotrienes, hydroxyeicosatetraenoic acids (HETEs), and lipoxins
- via cytochrome p50 – forms epoxides.
the cyclic (or cyclooxygenase) pathway of eicosanoids syntheis forms the (3)
prostaglandins,
thromboxanes and prostacyclins;
the linear (or lipoxygenase) pathway of eicosanoid synthesis forms
–> HPETE —-> leukotrienes, lipoxins, HETEs
the cytochrome P450 pathway of eicosanoid synthesis forms ___.
epoxides
(aspirin and other NSAIDs act on ____
cyclooxygenase (which converts converts arachidonic acid to PGH2)
cyclooxygenase converts __ to ___
arachidonic acid to PGH2
cyclooxygenase___ is tjhe form expressed in all tisues
cox-1
cyclooxygenase___ is tjhe form regulated by cytokines and growth factors.
it is inc in inflamattion
cox-2
___ is an irreversible inhbiitor of cox-1 and cox-2
aspirin
___ is an reverisible inhbiitor of cox-1 and cox-2
acetaminophen and ibuprofen
