Biosynthesis Of Fatty Acids Flashcards
Breakdown and synthesis of FAs are two separate pathways
What significant intermediate for synthesis is not present for breakdown and irreversible formation?
Malonyl coA
What are the active sites of acetyl coA carboxylase?
Biotin carboxylase domain
Activates co2
Attaches co2 to nitrogen in biotin ring with ATP help
Transcarboxylase domain
Transfers co2 from biotin to acetyl coA
Malonyl vs acetyl coA
Acetyl coA precursor
Just acetyl group plus s plus coA
Malonyl coA same as acetyl but plus co2
COOH group on end
Acetyl coA carboxylase differences in different species
Acetyl coA take hco3
Animal cells = cytoplasm for all steps
Bacteria = similar processs but separate polypeptide subunits for the three steps
Plants = both types
Why are fatty acids important?
Complex lipids components
E storage
Membrane structure
Signaling molecules
What is RLS for FA synthesis?
What is step stimulated by? Inhibited by?
Malonyl carboxylase synthesis
Stimulated by citrate
Inhibited by palmitoyl CoA
Biotinidase deficiency
Cannot recycle biotin
Enlarged liver and spleen
Dermatitis
Mammals FAS I details
Fatty acid synthase I
Multimeric complex = ensures efficiency
Only synthesizes even chain fatty acids
Sequence of events for FA synthase
KS = acetyl or Malonyl group added to ACP
condensation - co2 released (same co2 as added to acetylCoA in Acetyl coA carboxylase reaction)
KR = reduction of beta keto group (NADPH)
DH = dehydration - h2o released
ER = reduction of double bond (NADPH)
KS = translocation of butyryl group (resulting FA) to cys (SH) on KS
Recharge ACP with new Malonyl group
ACP Details
Contains covalent prosthetic group = 4’-phosphopantetheine = on ser side chain = vitamin B pantothenic acid
End of group is SH = how Malonyl groups are esterified
Delivers acetate (1st step) and malonate (following steps) to FaS
Shuttles growing chain through active sites during growth
MAT for FAS helps with what?
Charging of ACP
1 addition cycle for FAS
Adds two carbons
Uses 4H+ and 4e-
Releases 1CO2
Palmitate
16 C
Saturated
FAS I product
Palmitate production
8 acetyl coA + 7ATP + 14 NADPH + 14H+
—>
Palmitate + 8coA + 7ADP + 14 NADP + 6h2o
7 cycles acetylCoA carboxylase
7 cycles of condensation and reduction
How do liver cells Maintain high NADPH to NADP Ratio?
How do one do these things relate to FA synthesis?
PPP ox pathway
Malic enzyme = Malate to pyruvate
Pyruvate oxidation forms acetyl coA in mitochondrion
Also catabolism of AA carbon skeletons
Why is citric acid cycle important to FA?
Helps activate acetyl coA
Citrate production means acetyl coA —> coA-SH in mitochondrial Matrix
But
Citrate —> acetyl coA via citrate lyase in cytosol
Also produces OAA —> Malate
= RLS for FAS
Liver, Mammary gland, kidney primary NADPH source
PPP
Adipose tissue primary NADPH source
Malic enzyme
FAS NADPH sources and ratios
1:1 PPP to malic enzyme
What does citrate Allosterically activate.
What conditions encourage this?
Acetyl coA carboxylase
High ATP in mitochondria
High acetyl coA in mitochondria = more citrate produced
Citrate inhibits glycolysis enzymes
What deactivates acetyl coA carboxylase?
Implications?
Glucagon
Epinephrine
High AMP
Palmitoyl AMP = product of Malonyl coA?
Implication: FAS is inhibited
What does insulin activate?
Citrate lyase
= acetyl coA carboxylase production
= FAS activated
Thioesterase
Hydrolitic
Uses H2O to break palmitate from ACP
When FAS increased
What does this mean for E use?
Moving away from active E use, instead, E storage
What does Malonyl coA inhibit?
Fatty acid oxidation
Insulin and FAS
Synthesis is up
Breakdown is down
Insulin = in = keep E in
Glucagon and FA
Synthesis is down
Breakdown is up
Glucagon = glucose wagon = we want to use energy
How is FAS regulated?
NADPH availability - needed for condensation/ reduction cycle
ACC inhibited by glucagon, epinephrine
ACC activated by insulin and citrate
Elongases
Facilitate elongation…
Desaturation is reductive or oxidative?
Produces NADP
Oxidative
Carbon chains are reduced
How do NSAIDs inhibit inflammation
Aspirin = inhibits via acetylating essential ser residue in cyclo oexygenase h2 prostaglandin synthase (COX)
Ibuprofen/ naproxen = mimic substrate structure
ATP cost to transport 1 mitochondrial acetyl coA
1 atp
