Lipid Synthesis Flashcards
what are the fates of fatty acids?
triacylglycerol synthesis- storage or energy
phospholipid synthesis- membrane storage
other lipids
when are fatty acids made?
when carbohydrate consumption > immediate need
where does fatty acid biosynthesis occur?
liver
what initiates fatty acid biosynthesis?
high glucose flux- signals there is a lot of glucose, so citrate starts leaving the TCA cycle
what TCA cycle intermediate is used to make TAGs?
citrate
what are the steps of turning citrate into TAGs?
- citrate to acetyl-CoA and oxaloacetate via ATP citrate lyase
- acetyl-CoA to malonyl CoA by acetyl-CoA carboxylase
- malonyl CoA to palmitate by fatty acid synthase
- palimitate is modified or added directly to glycerol to make TAGs
what does ATP-citrate lyase do?
converts citrate to acetyl CoA
what does acetyl-CoA carboxylase do?
convert acetyl CoA to malonyl CoA
what does fatty acid synthase do?
converts malonyl CoA to palmitate
where are TAGs stored?
adipose tissue
what is the cofactor for ACBX? how does it work?
biotin interacts with the enzyme and gets a COO- from HCO3-
enzyme transfers the carboxyl from biotin to acetylCoA, adding the third carbon
how is ACBX regulated?
fed state- increased citrate, dephophorylation, decreased fatty acyl-CA
fasting state- decreased citrate, phophorylation, increased fatty acyl CoA
what is the first committed step of fatty acid biosynthesis?
acetyl CoA carboxylase reaction
what is the overall reaction for palmitate formation?
1 aceyl-CoA + 7 malonyl-CoA + 14NADPH –> palmitate + 14 NADPH + 7CO2 + 8CoA + 6H2O
what are the enzymes involved in palmitate formation?
malonyl/acetyl transferase
ketoacyl synthase
what is the cofactor involved in palmitate formation?
pantotheine arm, located in the middle of malonyl/acetyl transferase
what is the structure of malonyl/acetyl transferase?
7 catalytic sites on each of 2 subunits oriented oppositely toward each other
Pan-E arm moves substrates to each catalytic site
how many times is the cycle repeated until palmitate is formed?
7
what is the cycle of repeated steps?
- condensation- lose CO2
- reduction- via NADPH
- dehydration- lose H2O
- reduction- via NADPH
where do the substrates of fatty acid synthase come from?
malonyl CoA- acetyl carboxylase reaction
acetyl CoA- ATP citrate lyase reaction
NADPH- pentose shunt or malate conversion to pyruvate
what is elongation and desaturation of fatty acids?
adding carbons and double bonds to palmitate or essential fatty acids
why are fatty acids made longer and desaturated?
membrane fluidity- double bonds–>looser parking
- longer chains = more double bonds
make precursors for biologically active molecules
- eicosanoids
-TF ligand
-DAGs used in signaling
what is the only fatty acid that is made fully?
palmitate
what organisms make odd chain fatty acids? even?
prokaryotes make odd chain
animals make even chain
what is used to add double bonds at certain locations?
desaturases specific for a number of carbons from the delta end
what is linoleic acid?
18:2omega6
what is linolenic acid?
18:3omega3
how are the essential fatty acids modified?
start at delta6 desaturase step of palmitate conversion
delta6 desaturase–>elongation–>delta5 desaturase
(linolenic does another elongation and deta4 desaturase)
what are the essential fatty acids?
linoleic and linolenic
what desaturases do humans have?
delta9
delta6
delta5
delta4
what is delta6 deficiency?
low delta 6 desaturase deficiency
can’t change linoleic acid, linolenic acid, or palmitate to other fatty acids
what is palmitate the precursor for?
omega 9 family fatty acids
what class is palmitate?
saturated
what class is linolate?
omega 6
what class is linolenate?
omega3
what class does palmitate act as the precursor for?
omega 9
what is the product of palmitate elongation/desaturase used for?
make prostaglandins
what is the regulated step of fatty acid synthesis?
delta9 desaturase
essential fatty acids (linolate and linolenate) inhibit delta9 desaturase
also regulated by transcription (more in fed state)
what regulates transcription of the enzymes necessary for fatty acid synthase?
SREBP-1c
which enzymes are regulated by SREBP-1c?
acetyl-CoA carboxylase
fatty acid synthase
stearoyl-CoA desaturase
what happens to transcription in the fed state?
increased
what happens to transcription in the fasting state?
decreased
what happens to transcription in the presence of essential amino acids?
less transcription
how does SREBP-1c work?
- in ER membrane held by SCAP
-in presence of insulin, SREBP-1c is moved from ER to golgi
-S1p cleaves part of SREBp
S2p cleaves a helix loop helix
helix loop helix travels into nucleus and binds to the regulatory element of the lipogenic genes
what inhibits SREBP-1c?
polyunsaturated fatty acids (linolate and linolenate)
what stimulates SREBP-1c?
insulin
where are the 3 main sites of TAG synthesis?
intestine
adipose
liver
(mammary glands during lactation)
how is glycerol formed?
glucose–>dihydroxyacetone phosphate–>glycerol-3-phosphate
where is glycerol used directly? why?
liver because it has glycerol kinase
what are the steps of TAG formation?
glycerol-3-P + 2 fatty acids make phosphatidic acid via acyl transferase
phosphatidic acid - phosphate make DAG
DAG + FA makes TAG via acyl transferase
what is ApoB100?
protein used to make VLDL
what is VLDL? what is in it?
very low density lipoprotein
contains TAG and cholesterol
where is VLDL released?
into blood stream
what are the difference between ApoB48 and ApoB100?
ApoB48 is only in the intestinal and it is used to make chylomicrons which are secreted into lymphatic system
ApoB100 is in the liver and used to make VLDLs which are secreted into the blood
what happens to VLDL in the blood?
interacts with ApoCII/CIII and ApoE
binds to lipoprotein lipase
TAGs are removed
IDL- formed if some tags removed, cleared by liver or can rebind
LDL- formed if all Tags removed0 can be cleared by many tissues
*ApoE disassociates from LDL/IDL before recycling
