Fichas
Lecture 25 - Fatty Acid Synthesis
Fichas del conjunto (24)
- 1___ (__) 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 ___ ___Coenzyme A (COA)
fatty acids
Acetyl COA
malonyl COA - 2For 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) _________(ACP)
two
1) Condensation
2) Reduction
3) Dehydration
4) Reduction - 3Consider 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 ___NADPH
- 4Review 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 - ______Structure
triacylglycerols
waxes
steroids
eicosanoids
glycosphingolipids - 5Goals->Learn the biomolecules required to synthesize fatty acids
->Understand the 4 repeated reactions required to lengthen an acyl chain
by 2 carbons
->Learn key enzymes and how fatty acid synthesis is regulated
->Understand how fatty acids are activated and the role of elongases and
desaturases
->Understand pathways to make triacylglycerol and glycerophospholipids from fatty acids (including key intermediates) and the requirement for CTP - 6Fatty 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 ____acetyl COA
NADPH
cytoplasm - 7Fatty 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 ___2
repeat - 8Acyl groups are linked to ___ or ___ Build = ___ ___ Degrade = ___ ____COA or ACP
malonyl ACP
acetyl CoA - 9___-__ 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 ____Malonyl-ACP
acetyl-CoA carboxylase (ACC)
regulation
thioester - 101st 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 ACPCondensation
acetoacetyl (OR ketoacetyl)
2
any - 11—
- 12Fatty acid synthesis is catalyzed by ___ ___ __ (__ _) ->In eukaryotes it is a dimer of large 2500 amino acid proteins Fatty acid synthesis occurs in the ___fatty acid synthase (FAS I)
cytoplasm - 13__ 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 make16 & 18
longer
expensive - 14Regulation of fatty acid synthesis by regulation of ACC activity
- 15Free 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)lipids
activated
thioester
energy - 16Modifications 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 acidElongases
malonyl
desaturases
first
FAS II - 17Example 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 reducedEssential
double
reduced
malonyl
NADH - 18Most 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 glycerophospholipidsPhosphatidate
Phosphatidate - 19How to make triacylglycerol? l. Remove the phosphate from phosphatidate forming ___ (__) 2. Transfer acyl group from ___ ___ to the alcohol group of DAGdiacylglycerol (DAG)
acyl COA - 20How 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 sourceCTP
- 21How 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)CTP
diacylglycerol (DAG)
phosphatidylcholine
phosphatidylethanolamine - 22How to make phosphatidylserine? In most eukaryotes: phosphatidyl_____: serine Phosphatidylethanolamine transferase exchanges the ____ with serine to generate phosphatidylserine (PS)ethanolamine
ethanolamine - 23How to make other glycerophospholipids? l. React CTP with phosphatidate to form ___-____ 2. React CDP-diacylglycerol with serine or ____ to generate phosphatidylserine (PS) or _____ (__) respectivelyCDP-diacylglycerol
phosphatidylinositol (PI) - 24Recap ->___ & ___ 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 glycerophospholipidsAcetyl COA and NADPH
acetyl COA carboxylase (ACC)
Fatty acid synthase I (FAS I)
desaturated
CoA
stored
Phosphatidate
CDP