lipid synthesis: palmitate Flashcards
what is the shorthand name for palmitate
16:0
is palmitate saturated or unsaturated
saturated
is fatty acid synthesis endergonic or exergonic? what does this mean?
endergonic: requires ATP and reduced electron carriers
list 3 locations of high fatty acid synthesis
liver tissue, mammary glands, adipose tissue
T or F: fatty acid synthesis and breakdown are perfect opposites of each other
false; they are not opposite
describe why FA synthesis and breakdown are not opposites of each other
they are different pathways, require different enzymes, occur in different parts of the cell, and only FA synthesis requires malonyl-CoA
where in the cell does FA synthesis take place
cytosol
where in the cell does FA breakdown (oxidation) take place
mitochondrial matrix
from which two molecules is malonyl-CoA formed
acetyl-CoA and bicarbonate
how many carbons is malonyl-CoA
3C
how many carbons is acetyl-CoA
2C
how many carbons is bicarbonate
1C
T or F: the formation of malonyl-CoA from acetyl-CoA and bicarbonate is reversible
false; it’s irreversible
which enzyme creates malonyl-CoA from acetyl-CoA and bicarbonate
acetyl-CoA carboxylase
what does the formation of malonyl-CoA require
ATP
which cofactor does acetyl-CoA carboxylase have
biotin
which vitamin is biotin
B7
is biotin water soluble or water insoluble
water soluble
name the 3 enzyme domains of acetyl-CoA carboxylase
biotin carrier protein domain, biotin carboxylase domain, transcarboxylase domain
describe the arrangement of the 3 acetyl-CoA carboxylase domains in animals
they’re located on a single polypeptide
where is biotin attached to ACC
to the central biotin carrier protein domain
how is biotin attached to the biotin carrier protein domain of ACC
via an amide linkage to a lysine side chain
describe malonyl-CoA formation via ACC
CO2 from bicarbonate is attached to a nitrogen in the biotin ring in the biotin carboxylase active site. This requires ATP. Second, the carboxylated biotin swings to the transcarboxylase site, where the CO2 is transferred from biotin to acetyl-CoA to make malonyl-CoA. Finally biotin swings back to pick up another CO2 and repeat the process
how many steps is each 2C addition during FA synthesis
4 steps
which organism is fatty acid synthase I found in
vertebrates
describe the general structure of FASI
a single polypeptide chain with active sites on each of 7 domains
how do the domains function in FASI
they function as linked but distinct enzymes
T or F: in FASI, there are no intermediates released part way through the process, only the final 16:0 acyl chain
true
list the abbreviated versions of the 7 FASI enzymes
KS, MAT, DH, ER, KR, ACP, TE
which organisms is FASII found in
plants and bacteria
describe the general structure of FASII
the 7 enzyme domains are separate
T or F: FASII generates intermediates
true
list the names of the 4 steps needed to add 2C onto the malonyl group on ACP
condensation, reduction, dehydration, reduction
why do we need to join a 3C malonyl and a 2C acetyl to get a 4C intermediate, instead of just joining two 2C acetyl groups?
the decarboxylation of malonyl in step 1 dramatically decreases the free energy, making the reaction thermodynamically favorable
after palmitate is made, where does the first acetyl that was added end up
at the methyl end (C15 and C16)
after palmitate is made, where does the last malonyl group that was added end up
carboxyl end (C1)
before palmitate synthesis occurs, what must happen to the thiol groups of FASI
they must be “charged”
what is a thiol group
SH
during charging of the thiol groups, what happens to acetyl-CoA
it binds to a thiol group on a cysteine residue in the KS active site. This is done by MAT. Note: the CoA is not attached anymore
during charging of the thiol groups, what happens to malonyl-CoA
it binds to a thiol group on the ACP active site. This is done by MAT. Note: the CoA is not attached anymore
what is ACP called
acyl carrier protein
ACP has a prosthetic group derived from vitamin ___
B5
what is the role of ACP
acts as an arm that serves as an anchor for FASI
what type of domain is KS
a synthase domain
T or F: FASI will always be attached to ACP
true
after charging of the thiol groups, which step is next in FA synthesis
condensation
describe the condensation step of FA synthesis
KS catalyzes condensation: 2C acetyl from KS is brought to the malonyl on ACP = 4C intermediate (CO2 from malonyl is displaced)
during condensation of FA synthesis, where did the displaced CO2 come from originally
bicarbonate
after condensation, which step is next during FA synthesis
reduction
describe the first reduction during FA synthesis
KR catalyzes a reduction of the C3 carbonyl group (uses NADPH as an electron donor)
converts double bonded O into an OH
after the first reduction, which step is next during FA synthesis
dehydration
describe dehydration of FA synthesis
DH catalyzes dehydration to generate a double bond between C2 and C3
after dehydration, which step is next during FA synthesis
the second reduction
describe the second reduction of FA synthesis
ER catalyzes a reduction of the C2 double bond to make it a single bond (NADPH is the electron donor)
after the 4 steps of FA synthesis, what molecule do we have and where on FASI is it attached to
butyryl-ACP is the final product (4C)
T or F: once we have butyryl-ACP (after the first 4 steps of FA synthesis), we can start from the top
false; the ACP site is occupied so we need to move it first so the next malonyl can bind to ACP
where is butyryl-ACP transferred to after the first 4 steps of FA synthesis
KS
after butyryl has been moved from ACP to KS, what occurs?
just like before, MAT catalyzes the transfer of the malonyl from malonyl-CoA to the thiol group of the now empty ACP
with butyryl on KS and malonyl on ACP, describe what occurs during FA synthesis
butyryl on KS (4C) mimics the original acetyl group (2C) on KS. The 4 steps can now repeat, the chain growing by 2C every cycle
after the first 4 steps of FA synthesis, how many carbons are added to the chain per cycle?
2
how many cycles does it take to make palmitate
7
how is palmitate released from KS
TE domain releases palmitate via hydrolysis of the thioester bond (uses 1 water)
how many malonyl are needed to make palmitate
7
describe how much of each thing is required to make the 7 malonyl required for 1 palmitate
7 acetyl coA, 7 CO2, and 7 ATP needed to make 7 malonyl
how many of each molecule is needed to create 1 palmitate (via 7 cycles of ATP synthesis)
acetyl-CoA + 7 malonyl-CoA + 14 NADPH + 14H
what is the net amount of water leftover after palmitate is made
6 H2O
after FA synthesis, why do we have 6 water instead of 7?
1 molecule of water was required to hydrolyze the thioester bond that was attaching palmitate to KS
where does FA synthesis take place in plants
stroma of the cholorplast
where does FA synthesis take place in eurkaryotes
cytosol
list the 2 ways the cytoplasm of eukaryotes can generate lots of NADPH needed for FA synthesis
- pentose phosphate pathway
2 malic enzyme
describe the pentose phosphate pathway
glucose-6-phosphate is converted to ribulose 5-phosphate, which also produces 2 NADPH
why is the pentose phosphate pathway used in rapidly dividing cells
ribose is an end product, so it helps to keep up with the demand for nucleotides
describe the malic enzyme pathway
malate is converted to pyruvate via the malic enzyme, and 1 NADPH and 1 CO2 are produced
where is acetyl-CoA made
mitochondrial matrix
list 2 ways in which acetyl-CoA is made in the mitochondrial matrix
pyruvate oxidation and catabolism of amino acid skeletons
T or F: acetyl-CoA is able to leave the mitochondrial matrix
false; the mito matrix is impermeable to acteyl-CoA
describe how acetyl-CoA can overcome the inability to leave the mito matrix
citrate synthase converts acetyl-CoA to citrate by combining it with oxaloacetate. It can then use the citrate shuttle to get citrate out of the mitochondria, and it can reconvert to acetyl-CoA in the cytosol
T or F: after the citrate shuttle system, oxaloacetate is able to go back to the mitochondria
false; the mitochondria is impermeable to OAA
describe the 2 solutions to get OAA back into the mitochondria after the citrate shuttle system
- reduce OAA to malate via malate dehydrogenase and NADH. Then use the malate shuttle to get malate back to the mito, then reoxidize to get OAA
- reduce OAA to malate, then use malate to make NADPH and pyruvate via the malic enzyme (note: 1 CO2 is lost). Pyruvate can return to the matrix and then OAA can be regenerated via carboxylation
list 2 inhibitors of acetyl-CoA carboxylase
palmitoyl-CoA and glucagon
why is palmtioyl-CoA an inhibitor of FA synthesis
it’s a downstream product of malonyl-CoA, so when there is lots of it then there isn’t as much malonyl-CoA, so FA synthesis is inhibited
why is glucagon an inhibitor of FA synthesis
you don’t want to be building fats when you’re hungry
list 2 activators of acetyl-CoA carboxylase
citrate, insulin
why is citrate an activator of FA synthesis
it produces acetyl-CoA, so more acetyl-CoA = more FA synthesis
why is insulin an activator of FA synthesis
you want to be building fats after eating
T or F: FA synthesis can be regulated by gene expression
true
which family of transcription factors regulates expression of genes involved in fat metabolism based on dietary ingestion of lipids
PPAR
describe the role of PPAR after eating PUFAs
PUFAs bind to PPARs and PPARs supress the expression of lipogenic enzymes (so you make less PUFAs)
(eating PUFAs = you make less PUFAs)
describe the role of PPAR after eating lipids
PPARs activate genes that encode proteins required for proper lipid storage in adipocytes
(eating lipids = you store more lipids)
