LECTURE 19 - FATTY ACID SYNTHESIS Flashcards
where does fatty acid biosynthesis happen?
in the cytosol
issue: you need to export acetyl CoA to the cytoplasm, from the mitochondria
which metabolic circumstances require the synthesis of fatty acids?
to initiate cell division
after a glucose rich meal
after a fructose containing meal
which intermediate of the citric acid cycle is the starting point of FA synthesis?
citrate
FA synthesis turns on when you fill up the glycogen pool
how is acetyl CoA transported to the cytosol?
the citrate shuttle:
1. the CoA of acetyl CoA prevents it from crossing the mitochondria membrane
2. in the mitochondrium, acetyl CoA is converted to citrate by citrate synthase
3. citrate can cross the membrane without any issues
4. in the cytosol, citrate is converted to acetyl CoA and oxaloacetate by citrate lyase
what fatty acid is used as a building block?
palmitate
16C
saturated
what is the acetyl CoA carboxylase (ACC) reaction?
generates Malonyl CoA (3C) from Acetyl CoA (2C)
irreversible, rate limiting step of the synthesis of fatty acids
ATP breakdown provides the energy for the whole process to be exergonic
what are the two activities of ACC?
biotin carboxylase activity (this one needs a biotin as a cofactor) and transcarboxylase activity
what is the function of Malonyl CoA?
inhibits CPT1
turns off FA breakdown
what is ACP?
acyl carrier protein
what is the malonyl/acetyl CoA transacylase reaction?
couples acetyl CoA and malonyl CoA with ACP
this keeps acetyl and malonyl activated, prevents leakage to other compartments
makes Malonyl ACP and acetyl KS
what is the enzyme that synthesizes fatty acids?
fatty acid synthase (FAS)
how does synthesis of palmitate happen?
butyryl-KS (4C) is combined with malonyl ACP (2C), one CO2 is lost, to make a 3C compound
with every cycle, two carbons are added
this is all done by FAS
what is the structure of FAS?
very large protein
many domains
all catalytic activities are present on one monomer
two domains make thioester bonds (KS and ACP) and ACP is the main one
the substrates are passed on from active site to active site
2 homodimers organised in an upside down orientation
domains interact with each other
VERY FAST (less than a second from Acetyl CoA to palmitate)
what is invested/lost in one cycle of synthesis of palmitate?
2 NADPH used (from the PPP)
one CO2
what is the stoichiometry for the malonyl CoA reaction?
what is the overall stoichiometry for the palmitate synthesis?
