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___ (__) is a coenzyme that forms a thioester with fatty acids
Recall that __ ___ have a carboxylic acid group and an acyl group.
___ COA is required to synthesize fatty acids
The rate-limiting step in fatty acid synthesis is the conversion of acetyl COA into ___ ___
For fatty acid synthesis, the malonyl and acyl groups are bound by a thioester bond to an acyl carrier protein (___), instead of COA.
Fatty acid chains are synthesized by adding ___ carbons at a time.
There are 4 steps involved in growing a fatty acid chain by 2 carbons:
1) _________
2) _________
3) _________
4) _________
Consider an acyl chain 10 carbons long, extended to a 12 carbon acyl chain
Four steps
l. Condensation
2. Reduction
3. Dehydration
4. Reduction
Repeated to make longer fatty acid
Each reduction step requires ___
Review functions of lipids
_____ — e.g. plasma membrane — glycerophospholipids, sphingolipids, and cholesterol
Storage of energy — ____
Insulation
Protection of surface - ___
Regulation of metabolism - ____
Regulation of blood pressure, temperature, and contraction - ____
Cell recognition - ______
Goals
Fatty acid synthesis
Needs carbon — ____ __ — from the glycolytic and citric acid cycle — citrate is major source
Needs reducing power — ___ — from the pentose phosphate pathway
Occurs in ____
Fatty acids are synthesized and degraded by adding or removing __ carbons at a time.
For fatty acid synthesis
Four repeating steps — condensation, reduction, dehydration and reduction then ___
Acyl groups are linked to ___ or ___
Build = ___ ___
Degrade = ___ ____
___-__ is the substrate for fatty acid biosynthesis
Malonyl COA is generated from acetyl COA and bicarbonate.
Catalyzed by ___-___ ___
Irreversible reaction
*key to ____
Malonate group transferred to acyl carrier protein (ACP)
->Linked via ____
1st step = ______
First step is the generation of
____ ACP from acetyl ACP and malonyl ACP
Malonyl ACP only adds _ carbons at a time
BUT acetyl ACP can have __ number of carbons to combine to malonyl ACP
Fatty acid synthesis is catalyzed
by ___ ___ __ (__ _)
->In eukaryotes it is a dimer of
large 2500 amino acid proteins
Fatty acid synthesis occurs in the ___
__ and __ carbon fatty acids are made in eukaryotes longer side chains don't fit
Our enzyme can only accommodate 16 & 18 Carbon FA's (___ doesn’t fit)
Fatty acid synthesis is energy ____,
I palmitate — important to regulate
178 ATP to make
Regulation of fatty acid synthesis by
regulation of ACC activity
Free fatty acids — some are found but they are mostly incorporated into ____.
Free fatty acids must be ____ before they can be used.
Forms a ___ with CoA.
Activated because of high ___ bond (covalent attachment)
Modifications to fatty acids
How to make longer?
->___e xtend fatty acid by 2 carbons
->Uses ___ COA to extend
How to make unsaturated?
->In eukaryotes ___ form double bonds
->Unsaturated fatty acids are synthesized ___, then desaturated.
->In prokaryotes — uses __ __ — this enzyme can partially synthesize a fatty acid, create a double bond, then continue synthesis of the fatty acid
Example of elongation and desaturation
____ fatty acid — must come from the diet (note is activated here)
Desaturase introduces ___ bond-oxidation-consumes NADH
- molecular oxygen is ___
Elongation — ___ COA is used to add 2 more carbons
Reduction/dehydration/reduction step occurs-consumes ___
Desaturase introduces double bond-oxidation
- molecular oxygen is reduced
Most fatty acids are incorporated into triacylglycerol or glycerophospholipids
->2 acyl groups from acyl COA molecules are transferred to glycerol 3-
phosphate
->____ is the product
->____ is intermediate to make triacylglycerols or glycerophospholipids
How to make triacylglycerol?
l. Remove the phosphate from
phosphatidate forming ___ (__)
2. Transfer acyl group from
___ ___ to the alcohol group of DAG
How to make glycerophospholipids?
Step I — CTP reacts with alcohol phosphate to form a nucleotide alcohol derivative
Need __ (a nucleotide) to make glycerophospholipid as an energy source
How to make some glycerophospholipids?
l. React __ with alcohol phosphate
2. Remove the phosphate from
phosphatidate forming ___ (__)
3. Transfer the group from
the nucleotide alcohol derivative to the alcohol group of DAG releasing CMP to generate _____ (PC) or
______ (PE)
How to make phosphatidylserine?
In most eukaryotes:
phosphatidyl_____: serine
Phosphatidylethanolamine transferase exchanges the ____ with serine to generate phosphatidylserine (PS)
How to make other glycerophospholipids?
l. React CTP with phosphatidate to
form ___-____
2. React CDP-diacylglycerol with serine or ____ to generate phosphatidylserine (PS) or _____ (__) respectively
Recap
->___ & ___ are required for fatty acid synthesis
->Generation of malonyl COA by ___ ___ (__) is a key regulatory reaction
->____ catalyzes condensation (addition of 2 carbons), reduction, dehydration and reduction reactions in fatty acid synthesis
->Major products of FAS I can be elongated and/or ____
->Fatty acids are activated by ___
->Fatty acids are ___ as triacylglycerols or used to synthesize glycerophospholipids
->____ is key intermediate and a nucleotide (__) alcohol derivative is required for synthesis of glycerophospholipids
