Lecture 32: Lipid Anabolism Flashcards
Fatty Acid Synthesis Overview
Where does FA synthesis occur?
in the cytosol
Fatty Acid Synthesis Overview
What provides the first 2 carbons for the synthesis?
Acetyl-CoA
Fatty Acid Synthesis Overview
What provides the later carbons?
malonyl-CoA donating 2C units
Fatty Acid Synthesis Overview
What are immediates attached to on an acyl carrier protein (ACL)?
the -SH groups
Fatty Acid Synthesis Overview
What is the reductant in FA synthesis?
NADPH
Fatty Acid Synthesis Overview
When does elongation by the fatty acid synthase complex stop?
When it forms palmitate (C16)
further elongation and unsaturation is down by other enzyme systems
Fatty Acid Synthesis Overview
What is the multi-enam system for fatty acid synthesis called?
Enams can be in one polypeptide chain for higher organisms
Fatty Acid Synthase
Formation of Malonyl Coenzyme A
What is the commited step in FA synthesis?
Synthesis of malonyl-CoA
rate limiting step
Formation of Malonyl Coenzyme A
What is the equation involing malonyl-CoA synthesis?
Acetyl-CoA + HCO3 + ATP
-(acetyl-CoA carboxylase)->
Malonyl-CoA + ADP + Pi + H
Formation of Malonyl Coenzyme A
What controls the rate of FA biosynthesis?
acetyl-CoA carboxylase
Formation of Malonyl Coenzyme A
How is acetyl-CoA carbocylase activated/deactivated?
Activated: dephosphorylation
Deactivated: phosphorylation
Formation of Malonyl Coenzyme A
How are the intermediated linked to the ACP for transport?
covalently
Formation of Malonyl Coenzyme A
What is the enam called that links the acetyl/malonyl to ACP?
“Name” transacylase
ex: acetyl transacylase
ex: malonyl transacylase
Fatty Acid Synthesis
What is the overall goal of FA synthesis?
to attach 2 carbon acetate unit from malonyl-CoA to a growing chain then reduce it
Fatty Acid Synthesis
What are the 4 enzyme catalized steps of elongation cycles?
- Condensation (produce CO2 and ACP)
- Reduction (Uses NADPH, Produces NADP)
- Dehydration (Produces H2O)
- Reduction (Uses NADPH, Produces NADP)
Enzymes in Elongation Cycle
What is the enzyme in step 1?
Condensation
b-ketoacyl-ACP synthase (KS)
produces: acetoacetyl ACP
Enzymes in Elongation Cycle
What is the enzyme in step 2?
Reduction
b-ketoacyl-ACP reductase (KR)
produces: D-3-hydroxbutyryl ACP
Enzymes in Elongation Cycle
What is the enzyme in step 3?
Dehydration
b-hydroxyacyl-ACP dehydratase (DH)
produces: Crotonyl ACP
Enzymes in Elongation Cycle
What is the enzyme in step 4?
Reduction
enoyl-ACP reductase (ER)
Produces Butyryl ACP
Elongation Cycle
What does this elongation cycle look similar to?
The last 3 reactions are similar to the reverse of the fatty acid degradation, with some exceptions
* NADPH instead of NADH and FADH2
* D-enantiomer instead of L-enantiomer of hydroxybutarate
Elongation Cycle
What does the second cycle begin with?
the condensation of butyryl ACP and malonyl ACP (repeats cycle until reaching 16C, 7 cycles)
Elongation Cycle
What cleaves the palmityl-CoA from the ACP since it has reached 16C?
Thioesterase
Elongation Cycle
Where is further elongation and unsaturation happening?
in the endoplasmic reticulum by other enzymes
Elongation Cycle
What is the net equation of the synthesis of palmaitate from malonyl-CoA?
Acetyl CoA + 7 malonyl CoA + 14 NADPH + 20 H
–>
palmitate + 7 CO2 + 14 NADP + 8 CoA + 6 H2O
Elongation Cycle
What is the net equation of the synthesis of malonyl-CoA from acetyle-CoA?
7 Acetyl CoA + 7 CO2 + 7 ATP
–>
7 malonyl CoA + 7 ADP + 7 Pi + 14 H
Elongation Cycle
What is the net equation of the overall synthesis of palmitate from acetyl CoA in cytosol?
8 Acetyl CoA + 7 ATP + 14 NADPH + 6 H
–>
palmitate + 14 NADP + 8 CoA + 6 H2O + 7 ADP + 7 Pi
Citrate Shuttle
How are acetyl-CoA units moved out of the mitochondrial matrix (where they are formed) to the cytosol (to form fatty acids)?
As citrate: Acetyl-CoA reacts with oxaloacetate to form citrate
Citrate is cleaved by ATP-citrate lyase (consumes 1 ATP) to form back to acetyl-CoA and oxaloacetate
Biosynthesis of triaclglycerols and phospholipids
What are the two fates of newly synthesized FA in cells?
- Incorporated into tryacylglycerols for long term energy storage
- be incorporated into membrane phospholipids
Biosynthesis of triaclglycerols and phospholipids
What is the precursor for the backbone of fat and phospholipids?
glycerol-3-phosphate, which is derived from DHAP (intermediate of glycolysis)
Biosynthesis of triaclglycerols and phospholipids
How is phosphatidic acid formed?
Acyl transferases attach two fatty acids to glycerol-3-phosphate
Biosynthesis of triaclglycerols and phospholipids
What is phosphatidic acid the precursor for?
triacylglycerols and phospholipids
Biosynthesis of triaclglycerols and phospholipids
What is done to phosphatidic acid to make triacylglycerols?
It is dephosphorylated (by phosphotase) then acylated (by acyl transferase) to add third acylglycerol group
Biosynthesis of triaclglycerols and phospholipids
What is done to phosphatidic acid to make phospholipids?
Head group is attached onto phosphate
