Lipid Synthesis Flashcards

1
Q

what are the fates of fatty acids?

A

triacylglycerol synthesis- storage or energy
phospholipid synthesis- membrane storage
other lipids

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2
Q

when are fatty acids made?

A

when carbohydrate consumption > immediate need

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3
Q

where does fatty acid biosynthesis occur?

A

liver

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4
Q

what initiates fatty acid biosynthesis?

A

high glucose flux- signals there is a lot of glucose, so citrate starts leaving the TCA cycle

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5
Q

what TCA cycle intermediate is used to make TAGs?

A

citrate

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6
Q

what are the steps of turning citrate into TAGs?

A
  1. citrate to acetyl-CoA and oxaloacetate via ATP citrate lyase
  2. acetyl-CoA to malonyl CoA by acetyl-CoA carboxylase
  3. malonyl CoA to palmitate by fatty acid synthase
  4. palimitate is modified or added directly to glycerol to make TAGs
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7
Q

what does ATP-citrate lyase do?

A

converts citrate to acetyl CoA

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8
Q

what does acetyl-CoA carboxylase do?

A

convert acetyl CoA to malonyl CoA

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9
Q

what does fatty acid synthase do?

A

converts malonyl CoA to palmitate

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10
Q

where are TAGs stored?

A

adipose tissue

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11
Q

what is the cofactor for ACBX? how does it work?

A

biotin interacts with the enzyme and gets a COO- from HCO3-

enzyme transfers the carboxyl from biotin to acetylCoA, adding the third carbon

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12
Q

how is ACBX regulated?

A

fed state- increased citrate, dephophorylation, decreased fatty acyl-CA
fasting state- decreased citrate, phophorylation, increased fatty acyl CoA

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13
Q

what is the first committed step of fatty acid biosynthesis?

A

acetyl CoA carboxylase reaction

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14
Q

what is the overall reaction for palmitate formation?

A

1 aceyl-CoA + 7 malonyl-CoA + 14NADPH –> palmitate + 14 NADPH + 7CO2 + 8CoA + 6H2O

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15
Q

what are the enzymes involved in palmitate formation?

A

malonyl/acetyl transferase

ketoacyl synthase

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16
Q

what is the cofactor involved in palmitate formation?

A

pantotheine arm, located in the middle of malonyl/acetyl transferase

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17
Q

what is the structure of malonyl/acetyl transferase?

A

7 catalytic sites on each of 2 subunits oriented oppositely toward each other
Pan-E arm moves substrates to each catalytic site

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18
Q

how many times is the cycle repeated until palmitate is formed?

A

7

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19
Q

what is the cycle of repeated steps?

A
  1. condensation- lose CO2
  2. reduction- via NADPH
  3. dehydration- lose H2O
  4. reduction- via NADPH
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20
Q

where do the substrates of fatty acid synthase come from?

A

malonyl CoA- acetyl carboxylase reaction
acetyl CoA- ATP citrate lyase reaction
NADPH- pentose shunt or malate conversion to pyruvate

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21
Q

what is elongation and desaturation of fatty acids?

A

adding carbons and double bonds to palmitate or essential fatty acids

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22
Q

why are fatty acids made longer and desaturated?

A

membrane fluidity- double bonds–>looser parking
- longer chains = more double bonds
make precursors for biologically active molecules
- eicosanoids
-TF ligand
-DAGs used in signaling

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23
Q

what is the only fatty acid that is made fully?

A

palmitate

24
Q

what organisms make odd chain fatty acids? even?

A

prokaryotes make odd chain

animals make even chain

25
Q

what is used to add double bonds at certain locations?

A

desaturases specific for a number of carbons from the delta end

26
Q

what is linoleic acid?

A

18:2omega6

27
Q

what is linolenic acid?

A

18:3omega3

28
Q

how are the essential fatty acids modified?

A

start at delta6 desaturase step of palmitate conversion
delta6 desaturase–>elongation–>delta5 desaturase
(linolenic does another elongation and deta4 desaturase)

29
Q

what are the essential fatty acids?

A

linoleic and linolenic

30
Q

what desaturases do humans have?

A

delta9
delta6
delta5
delta4

31
Q

what is delta6 deficiency?

A

low delta 6 desaturase deficiency

can’t change linoleic acid, linolenic acid, or palmitate to other fatty acids

32
Q

what is palmitate the precursor for?

A

omega 9 family fatty acids

33
Q

what class is palmitate?

A

saturated

34
Q

what class is linolate?

A

omega 6

35
Q

what class is linolenate?

A

omega3

36
Q

what class does palmitate act as the precursor for?

A

omega 9

37
Q

what is the product of palmitate elongation/desaturase used for?

A

make prostaglandins

38
Q

what is the regulated step of fatty acid synthesis?

A

delta9 desaturase
essential fatty acids (linolate and linolenate) inhibit delta9 desaturase
also regulated by transcription (more in fed state)

39
Q

what regulates transcription of the enzymes necessary for fatty acid synthase?

A

SREBP-1c

40
Q

which enzymes are regulated by SREBP-1c?

A

acetyl-CoA carboxylase
fatty acid synthase
stearoyl-CoA desaturase

41
Q

what happens to transcription in the fed state?

A

increased

42
Q

what happens to transcription in the fasting state?

A

decreased

43
Q

what happens to transcription in the presence of essential amino acids?

A

less transcription

44
Q

how does SREBP-1c work?

A
  • 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
45
Q

what inhibits SREBP-1c?

A

polyunsaturated fatty acids (linolate and linolenate)

46
Q

what stimulates SREBP-1c?

A

insulin

47
Q

where are the 3 main sites of TAG synthesis?

A

intestine
adipose
liver
(mammary glands during lactation)

48
Q

how is glycerol formed?

A

glucose–>dihydroxyacetone phosphate–>glycerol-3-phosphate

49
Q

where is glycerol used directly? why?

A

liver because it has glycerol kinase

50
Q

what are the steps of TAG formation?

A

glycerol-3-P + 2 fatty acids make phosphatidic acid via acyl transferase
phosphatidic acid - phosphate make DAG
DAG + FA makes TAG via acyl transferase

51
Q

what is ApoB100?

A

protein used to make VLDL

52
Q

what is VLDL? what is in it?

A

very low density lipoprotein

contains TAG and cholesterol

53
Q

where is VLDL released?

A

into blood stream

54
Q

what are the difference between ApoB48 and ApoB100?

A

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

55
Q

what happens to VLDL in the blood?

A

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