Lecture 20: Fatty Acid Synthesis Flashcards
acetyl CoA carboxylase
key regulated enzyme in fatty acid synth
generates malonyl CoA using acetyl CoA
malonyl CoA
where the growing fatty acids attach
whats the reductant in fatty acid synth
NADPH
what moces the acetyl coA equivalents from the mitochondria to the cytosol
citrate shuttle
review table in slide
3
what is the common metabolite in both the synthesis and degradation pathways
acetyl CoA
why does it make sense that fatty acid degredation takes place in the mitochondrial matrix
NADH and FADH2 are produced
they’re ready to enter the ETS if they’re present
what purpose does fatty acid synth serve
convert excess acetyl CoA to fatty acids to be stored or exported (when glucose levels are high)
key enzymes in FA synth?
acetyl coA carboxylase
fatty acid synthase
is the energy charge high or low in the cell when excess acetyl-CoA is available for fatty acid synthesis?
high!
swinging arm mechanism
2 domain protein and biotin carrier
covalent linkages so intermediate doesn’t diffuse away
How many NADPH must be oxidized in the synthesis of C16 fatty acid palmitate shown on slide 11?
14
we need two every time we add 2 carbons
7 x 2= 14 NAPDHs
How many CO2 are released in this process and where are they coming from?
7 are released because we go through the process 7 times
they come from the malonyl CoA
review slides 10 and 11
review slides 10 and 11
there are 7 dehydration steps required for palmitiate synthesis
why only 6 NET H2O???
at the end of the cycle, we still have an acyl chain bound, but it takes water to release it
we produce 7 water molecules but we use one to release the chain
needed for final cleavage rxn to release palmitate from the ACP carrier protein
where do we add the carbon?
not at the end, but closer to the begining
write the reaction for synth of C18 stearate
__acetyl CoA + __ATP + __NADPH +__H+ —> sterate+__CoA+__ADP+__Pi+__NADP+ + __H2O
9 acetyl CoA +8 ATP + 16 NADPH +16 H+ —> sterate+9 CoA+8 ADP+ 8 Pi+ 16 NADP+ + 7 H2O
How do we move acetyl CoA
What do we do with it
we don’t directly transport it
use shuttle system
make it citrate that we move to cytosol
what do we do with the citrate we put it the cytosol
make OAA or carbon and acetyl CoA
make it to malate
2 things that can happen to malate
- transport back to matrix, covert to OAA
2. convert to pyruvate and also produce NADPH (one for every acetyl CoA equivalent)
where does most NADPH come from for fatty acid synth??
pentose phoshphate pathway (oxidative phase)
so lots of glucose 6 phosphate, make lots of NADPH
the bulk of NADPH needed for fatty acid synth actually comes from pentose phosphate pathway. Why does this make sense in terms of glucose 6 P lelvels
G6P levels are high during FA synth
we can do this and produce lots of NADPH
Metabolic reg of acetyl CoA carboxylase:
what stimulates
what inactivates
citrate activity stimulates
palmitoyl coA inhibits
BOTH ALLOSTERIC
why does it make sense that excess citrate activates acetyl CoA carboxylase activity?
high energy charge, so we need to start storing extra nrg just as fast
Why should palmotyl CoA inhibit enzyme activity?
palmitoyl CoA is in fatty acid degredation. Inhibits enzymes in order to inhibit simultaneous synth and degredation
Hormonal regulation of Acetyl-CoA carboxylase
glucagon
isnulin
citrate
explain the logic of insulin and AMP reg of acetyl CoA carboxylase
blood sugar levels high, stim by AMP b.c. low nrg charge
Why would high citrate levels partially activate the phosphorylated enzyme?
citrate=high nrg charge
allosteric reg=fast response (hormones are slow)
(review slide 18)
Glucagon signaling
cascade of rxns inside cell
AMPK (kinase) activated at the end–phosphorylates acetyl CoA carboxylase monomeric state
INACTIVATE
Citrate
polymerization
PARTIAL ACTIVITY
phosphorylated, so inactive, but citrate makes it partially active
Insulin signaling
protein phosphtase 2 stim: takes off phosphate
active state
ACTIVATE
AMPK
regulated by AMPKK (this one phosphorylates AMPK)
AMPKK inactivated by insulin
ensures acetyl-CoA carboxylase will stay in active conformation
review slide 19
review slide 20
review slide 20
