Mid 2: Lec 10 Flashcards
Where does fa biosynth take place
organs: liver, adipocytes
cell location: cytosol
coenzymes for FA biosynth and FA catab
biosynth: nadph
catab: nad+ and FAD
a coa path out of mit
tricarboxylate transport system
acetyl coa is turned to citrate in mit with citrate synthase
leaves mit
turned back to a coa with atp-citrate lyase
Starting substrates of the FA synthesis
acetyl coa: precursor
malonyl coa: c2 donor
Formation malonyl coa
Acetyl-CoA Carboxylase (ACC)
1: carboxylation
A bicarbonate ion is loaded on
the biotin prosthetic group
attached to ACC
biotin carboxylase activity of
ACC
2: transcarboxylation
The carboxyl group located on
the prosthetic biotin is
transferred to an acetyl-CoA
using the transcarboxylase
activity of ACC
The end product is Malonyl-CoA
Fatty acids synthesis loading of substrate
Fatty Acid Synthase (FAS) aka Megasynthase
1a: Conversion of acetyl-CoA into
acetyl-ACP
MAT
1b: Loading of the acetyl-ACP onto KS domain of FAS
2: Conversion of malonyl-CoA into
malonyl-ACP
MAT
FA synthesis: post-loading
Fatty Acid Synthase (FAS) aka Megasynthase
- -Decarboxylation and
condensation to form C-C
bond to make β-ketobutyryl-
ACP
-Catalyzed by KS - Reduction of β-keto group by Ketoacyl-ACP Reductase (KR) to make β- hydroxybutyryl-AC
- Dehydration of β-hydroxybutyryl-ACP by Hydroacyl-ACP
Dehydrase (DH) - Reduction of the double
bond by Enoyl-ACP
Reductase (ER) - Translocation of butyryl group to Cysteine on β-Ketoacyl- ACP
Synthase (KS)
Second round:
recharging of acp with a malonyl coa
malonyl added to chain with ks domain condensation, repeat until done
- Cleavage of thioester bond by TE
most common fa made in fa synth
palminate
c16:0
fatty acid elongation location and substrates and enzymes (gen)
ER and cytoplasm
uses product of FAS (palminate)
extends with malonyl coa
multiple enzymes
Fatty acid desaturation double bond types. Where do other types of unsat fas come from
delta 5, delta 6, delta 9
essential fatty acids (e.g. omega 3 FA)
FA synth reg
Acetyl-CoA Carboxylase (ACC) catalyzes the rate limiting
step of fatty acid synthesis
allosteric control:
-positive: citrate
-negative: fatty acyl-Coa
covalent control:
-phosphorylation due to low atp, low glucose, or fight/flight conditions leads to reduced fa synth
-dephosphorylation results from high glucose, insulin, and stim of PP2a. Increase in fa synth
fa synth reciprocal regulation
malonyl coa from fa synth inhibits cpt1 so b-oxidation does not occur when fa is being synthed
high fa conc seppresses fa synth by blocking malonyl coa formation at level of acc
b-ox and fa synth c2 units
b-ox: acetyl coa (product)
fa synth: malonyl coa (donor)
b-ox and fa synth acyl carriers
b-ox: CoA-SH
fa synth: ACP
