___ (__) 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

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