fatty acid synthesis (13) Flashcards
what organ are fatty acids synthesized in?
the liver
when acetyl coA is in high concentration, what enzyme is inhibited?
pyruvate dehydrogenase
what enzyme is inhibited when there are low levels of acetyl coA?
pyruvate carboxylase
what enzyme cleaves citrate in the cytosol to acetyl coA and OAA?
citrate lyase
where can the enzyme pyruvate dehydrogenase be found (what part of the cell)
ONLY in the mitochondria
can acetyl coA cross the mitochondrial membrane?
HELLL NO
what are the 2 sources of NADPH that is necessary for the synthesis of fatty acids?
- recycling of OAA
2. pentose phosphate shunt
what are the two steps of OAA recycling?
- OAA is reduced by an NADH dependent cytosolic malate dehydrogenase to malate
- Malate is then converted by the NADP+ dependent malic enzyme which oxidizes & decarboxylates malate to pyruvate
what are the two enzymes necessary for fatty acid synthesis?
acetyl coA carboxylase-ACC
fatty acid synthase-FAS
which enzyme is the rate controlling step in fatty acid synthesis?
ACC
what reaction does ACC catalyze?
the addition of a carboxyl group from acetyl coA onto malonyl coA
what is ACC’s cofactor?
biotin
what does biotin bind in the presence of ATP during the ACC reaction?
binds CO2
list the positive regulators of ACC (2)
- citrate causes ACC to polymerize (activates ACC)
- insulin stimulates phosphatase which dephosphorylates ACC to its active state)
list the negative regulators of ACC (3)
- palmitoyl coA (feedback inhibition)
- glucagon & epinephrine phosphorylate ACC
- AMP (indicates low energy levels)
what are the 5 steps of fatty acid synthesis
- activation
- condensation
- reduction
- dehydration
- reduction
what enzyme catalyzes step 1 of fatty acid synthesis?
ACC
what enzyme catalyses steps 2-5 of fatty acid synthesis?
FAS
what enzyme of fatty acid synthesis does this action describe?
“adds two carbon units form malonyl coA to the growing fatty acyl chain with the final product being palmitiate”
FAS
describe what is happening in the 2nd step of fatty acid synthesis the condensation step
- acetyl group from acetyl coA first associates with the ACP phospho-pantetheinyl sulfhydryl group and then is transferred to the cysteine sulfhydryl of the other subunit
- malonyl from malonyl coA then associates with ACP phospho-pantetheinyl sulfhydryl group
- the malonyl and the acetyl groups condense with the release of the malonyl carboxyl group as CO2
what is the product of the condensation step, step 2 of fatty acid synthesis?
a 4 carbon ß-keto acyl chain which is attached to the ACP phospho-pantetheinyl sulfhydryl group
what step does the following describe
“reduction of the beta-keto group to an alcohol”
step 3, reduction step
what molecule provides the reducing equivalents for steps 3 through 5?
NADPH
where are fatty acids elongated (within the cell)
in the ER
what is the major elongation that occurs in the body?
palmityl coA to sterayl coA (18 carbons)
what is fatty acid desaturatoin?
the oxidation of fatty acids resulting in cis double bonds
it creates lipids of increasing structural and functional complexity with distinct biological roles
where are desaturases located?
in the ER of a cell
what 3 things do desaturases require?
O2, NADH and cytochrome b5
what happens to desaturase activity during starvation?
their activity sharply decreases
what happens to desaturase activity when large amounts of unsaturated fats are eaten?
desaturase activites descrease
what 3 distinct desaturases do humans have?
∆9 desaturase
∆6 desaturase
∆5 desaturase
what type of PUFAs does fish oil contain?
ω3 and ω6 PUFAs
why isn’t arachidonic acid considered an essential fatty acid?
because of linoleic acid is present (which is essential) the body can synthesize it
list the 3 things that arachidonic acid is considered a substrate for
leukotrines, thromboxanes &prostaglandin
name some things that eicosanoids are involved in
inflammatory response
smooth muscle contraction
brococonstriction/dilation
what are the 3 pathways for eicosanoids syntheiss?
- cyclic (cyclooxygenase) pathway
- linear (lipoxygenase) pathway
- cytochrome P450 pathway
what does the cytochrome P450 pathway form?
epoxides
what does the linear pathway form?
leukotrines, HETEs and lipoxins from a common intermediate HPETE
what does the cyclic pathway form?
prostaglandins, throboxanes and prostacyclins
what enzyme does aspirin and other NSAIDs act on?
COX enzyme
what is the function of the COX enzyme?
convert arachidonic acid to PGH2
COX1 or COX2 which does the following describe
“ the consitiutive form expressed in all tissues”
cox1
describe cox 2
the inducible form regulated by a variety of cytokines and growth factors
increased in response to inflammation
which of the following are irreversilbe/reversilbe inhibitors of COX1 and COX2
aspirin
acetaminophren
ibuprofen
aspirin- irreversible inhibitor
acetaminophren- reversible inhibitor
ibuprofen- reversible inhibitor
