lecture 7: lipid metabolism Flashcards
primary sites for fatty acid synthesis
liver and adipose tissue, produced in response to excess calories
enzymes carrying out FA synthesis are located in
the cytoplasm
(oxidative enzymes in mitochondrial matrix)
what is the building block of FAs?
acetyl CoA
formed in the mitochondria from pyruvate
how is acetyl CoA made available if it can’t be shuttled into cytosol?
acetyl CoA converted into citrate, citrate transported into cytosol, then converted back to acetyl CoA
when might acetyl CoA levels be high?
fed state > ATP levels saturated > citric acid cycle inhibited > citrate not metabolized > goes to cytosol for Acetyl CoA transfer
Where does malate from acetyl coA transfer go?
shuttled back to mitochondria to make citrate, or undergo oxidative decarboxylation yielding NADPH and CO2
once acetyl CoA is in the cytosol, how does it synthesis into FA?
acetyl CoA carboxylase and FA synthase complete process to form palmitate
acetyl-CoA carboxylase
acetyl CoA to malonyl CoA using ATP carboxylation
dependent on cofactor biotin
activated by citrate, inhibited by FAs
fatty acid synthase
synthesizes palmitate from malonyl CoA and acetyl CoA
sequence of rxns: condensation, reduction, dehydration, reduction
7 malonyl CoA + 1 acetyl CoA + 14 NADPH + 14 H+ > 1 palmitate + 8 CoA + 7 CO2 + 14 NADP+ + 6H2O
when is fatty acid synthase activity low/high?
low in fasted state, increases in fed state
acetyl-coA carboxylase immediate regulation of synthesis
malonyl CoA as a regulator
inhibitor of CPT1 (transfers FA into mitochondria for oxidation)
ensures that FA synthesis and oxidation don’t occur simultaneously
elongation of FAs
malonyl CoA (elongating group) and long chain acetyl CoAs (reaction primer)
regulation of acetyl-CoA carboxylase
allosterically activated by citrate, inhibited by FAs
subject to regulation via phosphorylation > less active
AMP (low energy charge) activates AMPK > AMPK phosphorylates acetyl-CoA carboxylase
AMPK inhibits FA synthesis
desaturation of FAs
occurs in ER
∆9 desaturase complex introduces double bond at ∆9 position, oxygen as electron acceptor, generates 2 water molecules and a double bond
polyunsaturated fatty acids can be produced by…
adding additional double bonds by other desaturases
lack of desaturases > some polyunsaturated FAs must be obtained through diet
oxidation of FAs
129 ATP after complete oxidation of palmitate
7 cycles of B-oxidation
oxidation of FAs with odd number carbons
final cleavage is 1 acetyl CoA and 1 propionyl CoA (instead of 2 acetyl-CoA), which is converted into succinyl CoA (CAC intermediate)
palmitate
most common saturated fatty acid, 16 C
when citrate levels are elevated…
translocation to cytosol facilitated in exchange for malate
this malate then goes to make citrate again or to make NADPH
where does malate in the citrate shuttle come from?
cleaved from oxaloacetate
oxaloacetate can be produced from citrate once it enters cytosol
palmitate synthesis
1) acetyl-CoA transfer via citrate shuttle
2) convert acetyl-CoA to malonyl-CoA
3) synthesize palmitate from malonyl-CoA and Acetyl-CoA
CPT1
transfers FAs to mitochondria for oxidation
inhibited by malonyl-CoA
first step of oxidation of fatty acids
transfer FA into mitochondria (inhibited by malonyl-CoA)
what are the products of palmitate oxidation? (7 cycles)
8 acetyl-CoA, 7NADH, 7 FADH2
