fatty acid synthesis

glycogen is like cash how?
glycogen is similar to cash in that it is readily available
how are fats like savings accounts?
fats take a little more energy to save for later and utilize
what are the things that need to be in place before fatty acid synthesis? (substrates)
Acetyl CoA, (however it needs to be in cytosol). ATP, (coming from glucose – substrate phosphorylation). Reducing power, (NADPH’s are used for reducing power of synthesizing something – from PPP/malic enzyme). Finally, glycerol backbone is needed for TG synthesis
glycolysis is the oxidation of ____ to ____
glucose to pyruvate
fatty acid synthesis is the reduction of ______ to _______
acetyl CoA to fatty acids
once glucose is converted, (via glycolysis), to pyruvate, (in the mitochondria)which gives acetyl CoA, how does acetyl CoA get to fatty acid synthesis?
acetyl CoA cannot pass the mitochondrial membrane, it is combined with oxaloacetate to make citrate which can cross the mitochondrial membrane. citrate lyase then breaks citrae back down into oxaloacetate and acetyl CoA, (for fatty acid synthesis)
once the 3 carbon oxaloacetate is brought into the cytosol as citrate, how is it made back into a 3 carbon molecule pyruvate?
cytosolic malic dehydrogenase reduces it to malate, then malic enzyme removes a carbon along with producing a NADPH, to create pyruvate
what 2 enzymes are inducible in the OAA recycling step? what are they induced by?
citrate lyase and malic enzyme. they are induced by the presence of carbohydrates.
what is the significance of NADH being used and NADPH being created in the OAA -> pyruvate recycling step? where else can NADPH come from?
NADH is basically traded for NADPH, which is needed for lipogenesis. NADPH can also come from the PPP, via action of G6P dehydrogenase
what does excess glucose mean in terms of the TCA cycle, electron transport chain, and citrate levels?
TCA cycle and electron transport chain are running at a high rate, and there is excess citrate available in the cytosol
once acetyl CoA is available in the cytosol, what is the first step of fatty acid synthesis? what is the cofactor needed? is this step regulated?
the 1st step of fatty acid synthesis is acetyl CoA -> malonyl CoA, (job is to become fat). biotin is a necessary cofactor and this is a regulatory step.
what kinds of enzymes use biotin as a cofactor?
what happens in the conversion of acetyl CoA to malonyl CoA?
carboxylase with the help of biotin adds a carboxyl group, (2C acetyl CoA to 3C malonyl CoA)
what is the enzyme used in the second phase of fatty acid synthesis, (malonyl CoA -> palmitate), what is its structure like?
fatty acid synthase is a dimer of identical subunits, each with seven enzyme activities. it also has 2 arms, ACP, (acyl carrier protein, it has an -SH group), and a cysteine residue, also w/a -SH group
where does acetyl CoA bind on FA synthase?
both -SH groups at various times during the process
how is FA sythase primed?
by addition of acetyl CoA to the acyl carrier protein, (only time acetyl CoA is added to this enzyme)
once FA synthase is primed, what happens?
the acetyl CoA is shifted to the cystiene arm, and malonyl CoA is added to the acyl carrier protein arm.
how do the acetyl, (cystiene arm), and malonyl group, (acyl carrier protein arm), interact?
the carboxylate group is removed from the end of malonyl, (released as CO2 -> condensation rxn), the ketone group of the acetyl detaches from the enzyme and attaches and the next methylene group on the malonyl.
what happens to the 4C keto chain formed from the addition of the acetyl group to the malonyl?
it is reduced, dehydrated, and reduced again, USING NADPH for the reduction steps, this creates a 4C saturated chain w/the a ketone group nearest to the FA synthase, ready to detach and attach to the methylene group of the next malonyl group added -> process repeats itself until 16C
what carbon remains on the end of the forming palmitate molecule the entire time it is being switched back and forth between the ACP and cystiene arms and malonyl groups are added?
the omega carbon from the intial acetyl CoA added in the first step
how do beta-oxidation and fatty acid synthesis compare?
they are similar processes, but in reverse. beta-oxidation produces reducing equivalents, (FADH/NADH), oxidizes fats, adds water and produces acetyl CoA. fatty acid synthesis uses reducing equivalents, reduces fats, loses water, condenses/decarboxylates, and starts with Acetyl CoA.
can FA synthases make shorter FA chains than 16C?
yes, it can drop off earlier to create SCFAs and MCFAs
can FA synthase make double bonds?
where does FA synthase function?
in the cytosol
how is palmitate prepared before it can be elongated?
acyl CoA synthtase attaches a CoA to the palmitate, (instead of ACP/cystiene groups w/FA synthase)
how is palmitate elongated? where does this occur?
FA elongase, located in the ER, adds malonyl groups in the same fashion they were added via FA synthase
other than elongation, what else can happen to palmitate? what does this and where?
desaturation, addition of double bonds via fatty acyl CoA desaturase in the ER
what does fatty acyl CoA desaturase do?
fatty acyl CoA desaturase oxidizes both the fatty acid and O2, creating double bonds and H2O
what is a limitation of fatty acyl CoA desaturase?
fatty acyl CoA desaturase cannot desaturate past carbon 8
due to the limitation of fatty acyl CoA desaturase what essential fatty acids are necessary to the human diet?
linoleic and linolenic
what important fatty acid is made from an essential fatty acid? what is it needed for?
linoleic acid (omega 6) is converted to arachidonic acid by unsaturating the 6 carbon. it is needed for platelets
what step/enzyme of fatty acid synthesis is regulated?
acetyl CoA to malonyl CoA via acetyl CoA carboxylase
what is the first way fatty acid synthesis is regulated? (short term)
citrate activates acetyl CoA carboxylase by making it a polymer and long chain fatty acyl, (palmitoyl CoA) inhibits it by making the enzyme a monomer
what is the second way that fatty acid synthesis is regulated? (short term)
high glucagon activates a cAMP dependent protein kinase A, (PKA), to phosphorylate acetyl CoA carboxylase, INACTIVATING IT, (want to use energy not store it). high insulin activates a phosphatase, (PKA), to dephosphorylate acetyl CoA carboxylase, ACTIVATING IT, (want to store energy not use it).
what is the third way that fatty acid synthesis is regulated? (long term)
enzymes such as acetyl CoA carboxylase, FA synthase, citrate lyase, malic enzyme, G6PDH are induced if pt has good diet/high carb OR low fat diet. these enzymes are decreased if fasting or high fat diet
how does malonyl CoA prevent a futile cycle where FA breakdown and synthesis occur at the same time?
malonyl CoA prevents FAs from being transferred to carnitine and entering the mitochondria where beta oxidation occurs
once fatty acids have been produced what happens to them? are there different processes dependent upon location?
fatty acids are made into trigylcerides. in adipose tissue, (and liver), DHAP, (glycolytic substrate from when 6C -> 2 3C molecules), can be used to make glycerol-3P, (via glycerol P dehydrogenase), which then just needs 3 fatty acids added to it. exclusively in the liver, glycerol it self can be used b/c it only has glycerol kinase to produce Glycerol-3-P
how does the lack of glycerol kinase in adipose prevent a futile cycle?
glycerol kinase can make TGs w/out excess glucose in the liver if needed. adipose only needs to make TGs, (for storage), if there is plenty of glucose in the system, and it gets its glycerol backbone from a side product of glycolysis -> glycerol 3 phosphate
once TGs are made and need to be sent to the bloodstream, where do they go in the cell?
TGs are sent to the golgi complex to form very low density lipoproteins, (VLDL).
what are VLDL composed of? where are they made?
VLDLs are composed of proteins, (Apo B100), and trigycerides. they are synthesized in the golgi complex -> secreted in secretory vesicles via exocytosis
how do the genes for Apo B100, (VDLD, liver) and Apo B48, (chylomicrons, intestinal cells), compare?
the genes for Apo B100/VDLD and Apo B48/chylomicrons come from the same gene, but they have tissue specific transcripts due to RNA editing, (Apo B48 has a smaller gene)
where do VLDLs go once released into the bloodstream by the liver?
they travel until they hit lipoprotein lipase in capillaries outside target organs, which breaks down the VLDL and TGs, releasing the FAs which are absorbed by the cell and then reformed into TGs once inside
what stimulates the storage of FAs as TGs in adipose tissue? how?
insulin stimulates transport of glucose into the adipose cells, (via Glut4) which runs through glycolysis, producing DHAP, (Dihydroxyacetone phosphate), which becomes the glycerol backbone of TGs formed by the FAs
how does insulin affect the lipoprotien lipases?
insulin stimulates the synthesis and secretion of LPLs
what needs to happen to the VLDLs, (very low density lipoproteins), before they can interact with the lipoprotein lipase?
HDLs give VLDLs ApoC, (just like chylomicrons), which activates lipoprotien lipases