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biochem block 3 > fatty acid synthesis > Flashcards

fatty acid synthesis Flashcards

1
Q

what will stimulate lipogenesis?

A

insulin

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2
Q

why is lipogensis greater in high carbohydrate v.s high fat diets?

A

carbohydrates provide all of the components needed (glycerol and acetyl-CoA) whereas fat only provides acetyl-CoA

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3
Q

3 sites for lipogenesis in humans

A
  • liver (main site)
  • adipose tissue
  • lactating mammary gland
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4
Q

what is the most common FA synthesized in the body? exception?

A

m/c is palmitiate (16:0), except for lactating mammary gland which will make C8-C12

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5
Q

what is the significance of mammary gland synthesizing medium chain FA?

A

medium chain FA do not require carnitine shuttle, this is important bc infants have immature livers and thus low supply of carnitine

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6
Q

elongation of palmitate =

A

stearate (18:0)

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7
Q

shortening of palmitate =

A

myristate (14:0)

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8
Q

where in the cell does FA synthesis occur?

A

in cytosol, important to keep it separated from FA oxidation occurring in the mitochondria

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9
Q

what reducing agent is used in FA synthesis?

A

NADPH

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10
Q

what is the first committed step of FA synthesis? cofactor? enzyme?

A

formation of malonyl-CoA from acetyl-CoA + CO2, biotin cofactor, enzyme is acetyl-CoA carboxylase , uses 1 ATP

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11
Q

what enzymes are used to transfer malonyl-CoA and acetyl-CoA to ACP?

A

malonyl-transferase or acetyl-transferase

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12
Q

what is the product of condensation between acetyl-CoA and malonyl-CoA?

A

acetoacetyl-CoA (by acyl-malonyl ACP condensing enzyme)

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13
Q

what are steps 4-6?

A

4- reduction with NADPH
5- dehydration
6- reduction with NADPH

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14
Q

what steps are repeated for elongation?

A

4-6

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15
Q

what is the resulting compound after one round of reactions?

A

butyryl-ACP

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16
Q

what will be added to butyryl-ACP for elongation?

A

malonyl-ACP

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17
Q

at which end does elongation occur?

A

carboxyl terminal

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18
Q

what enzyme will release the FA from ACP once synthesis is complete?

A

thioesterase

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19
Q

how many acetyl-CoA, NADPH and ATP required for 1 molecule of palmitate?

A

8 acetyl-CoA
14 NADPH
7 ATP

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20
Q

why are 7 ATP needed to make 1 molecule of palmitate?

A

each malonyl-ACP required uses 1 ATP to synthesize from acetyl-CoA

21
Q

describe fatty acid synthase

A

multi-unit enzyme complex with 7 “activities” on 1 enzyme complex

22
Q

describe the overall regulation of fatty acid synthase

A

under transcriptional regulation

23
Q

describe fatty acid synthase regulation in liver

A

regulation by insulin = increased expression through USFs and SREBPs

24
Q

what is the action of PUFAs on fatty acid synthase regulation

A

polyunsaturated FAs decrease fatty acid synthase expression through suppression of SREBP production

25
Q

describe fatty acid synthase regulation in adipose cells

A

regulation by leptin = inhibits SREBP-1 expression and thus decreases fatty acid synthase expression

26
Q

how/why is leptin produced?

A

produced in fat cells in response to excess fat storage

27
Q

ow does leptin regulate body weight? (3)

A
  • decreases food intake
  • increases energy expenditure
  • inhibits FA synthesis
28
Q

how does acetly-CoA reach the cytosol?

A

acetyl-CoA is produced in mitochondria but needs to be in cytosol for FA synthesis, it is transported to cytosol via citrate carrier

29
Q

how does the citrate carrier work? (6)

A
  • in mito, acetyl-CoA is converted to citrate
  • citrate passes through mito membrane into cytosol
  • citrate + ATP in cytosol yield oxaloacetate and acetyl-CoA
  • malate dehydrogenase (using NADH) will convert oxaloacetate to malate + NAD+
  • malic enzyme (using NADP+) will convert malate to pyruvate + NADPH + CO2
  • pyruvate will travel back into mitochondria where it is converted back to oxaloacetate by pyruvate carboxylase
30
Q

what are 2 sources of NADPH in the cell?

A

1- PPP (oxidative portion)

2- malic enzyme pathway

31
Q

what is the major regulated enzyme in FA synthesis?

A

acetyl-CoA carboxylase

32
Q

what is the consequence of phosphorylation on acetly-CoA carboxylase?

A

since FA synthesis is anabolic, when acetyl-CoA carboxylase is phosphorylated, it is inhibited

33
Q

what will phosphorylate/inactivate acetyl-CoA carboxylase?

A

Protein Kinase A

stimulated by glucagon/epinephrine –> cAMP

34
Q

what will dephosphorylate/activate acetyl-CoA carboxylase?

A

protein phosphatase (stimulated by insulin); dephosphorylated form is highly active even in the absence of citrate

35
Q

what local metabolite exerts allosteric control on acetyl-CoA carboxylase?

A

citrate promotes activity of acetly-CoA carboxylase by enabling it to form polymers; citrate can partially overcome inhibition caused by phosphorylation

36
Q

how are FA longer than C16 formed in the body?

A

enzymes present on the cytosolic surface of the ER add 2C units (from malonyl-CoA)

37
Q

what enzymes are responsible for desaturation?

A

desaturases present on the inner ER membrane surface in a “mini-ETC”

38
Q

what are the components of the mini-ETC?

A

1- NADH cytochrome b5 reductase (FAD –> FADH2)
2- cytochrome b5 (Fe)
3- desaturase (Fe)

39
Q

overall reaction for conversion of stearate (18:0) to oleate (18:1 cis D9)

A

sterate +NADH + O2 –> Oleate + NAD+ + H2O

40
Q

where is FA oxidation controlled?

A

at the level of the carnitine shuttle (CPT1)

41
Q

where is FA synthesis controlled?

A

at the level of acetyl-CoA carboxylase

42
Q

what is the “general pathway” for storage of synthesized fatty acids as triglycerides?

A
  • glycerol-3-P + acyl-CoA =
  • lysophosphatidic acid + acyl-CoA =
  • phosphatidic acid - PO4 =
  • 1,2-DAG + acyl-CoA =
  • TAG
43
Q

what tissues will use the “general pathway”?

A

liver and adipocytes

44
Q

what is the source of glycerol-3-P?

A

synthesized from glucose via glycolysis steps

glucose –> DHAP –> G3P

45
Q

what is unique of TAG synthesis in the small intestine?

A

small intestine will re-aceylate 2-MAG

46
Q

differences between b-oxidation and FA synthesis: location

A

b-oxidation: mitochondria

FA synthesis: cytosol

47
Q

differences between b-oxidation and FA synthesis: group carrier

A

b-oxidation: CoA

FA synthesis: ACP

48
Q

differences between b-oxidation and FA synthesis: electron donor/acceptor

A

b-oxidation: FAD, NADH

FA synthesis: NADPH

49
Q

differences between b-oxidation and FA synthesis: unit product/donor

A

b-oxidation: Acetyl-CoA

FA synthesis: Malonyl-CoA

biochem block 3 (7 decks)

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