fatty acid synthesis Flashcards

(49 cards)

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
describe fatty acid synthase regulation in adipose cells
regulation by leptin = inhibits SREBP-1 expression and thus decreases fatty acid synthase expression
26
how/why is leptin produced?
produced in fat cells in response to excess fat storage
27
ow does leptin regulate body weight? (3)
- decreases food intake - increases energy expenditure - inhibits FA synthesis
28
how does acetly-CoA reach the cytosol?
acetyl-CoA is produced in mitochondria but needs to be in cytosol for FA synthesis, it is transported to cytosol via citrate carrier
29
how does the citrate carrier work? (6)
- 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
what are 2 sources of NADPH in the cell?
1- PPP (oxidative portion) | 2- malic enzyme pathway
31
what is the major regulated enzyme in FA synthesis?
acetyl-CoA carboxylase
32
what is the consequence of phosphorylation on acetly-CoA carboxylase?
since FA synthesis is anabolic, when acetyl-CoA carboxylase is phosphorylated, it is inhibited
33
what will phosphorylate/inactivate acetyl-CoA carboxylase?
Protein Kinase A | stimulated by glucagon/epinephrine --> cAMP
34
what will dephosphorylate/activate acetyl-CoA carboxylase?
protein phosphatase (stimulated by insulin); dephosphorylated form is highly active even in the absence of citrate
35
what local metabolite exerts allosteric control on acetyl-CoA carboxylase?
citrate promotes activity of acetly-CoA carboxylase by enabling it to form polymers; citrate can partially overcome inhibition caused by phosphorylation
36
how are FA longer than C16 formed in the body?
enzymes present on the cytosolic surface of the ER add 2C units (from malonyl-CoA)
37
what enzymes are responsible for desaturation?
desaturases present on the inner ER membrane surface in a "mini-ETC"
38
what are the components of the mini-ETC?
1- NADH cytochrome b5 reductase (FAD --> FADH2) 2- cytochrome b5 (Fe) 3- desaturase (Fe)
39
overall reaction for conversion of stearate (18:0) to oleate (18:1 cis D9)
sterate +NADH + O2 --> Oleate + NAD+ + H2O
40
where is FA oxidation controlled?
at the level of the carnitine shuttle (CPT1)
41
where is FA synthesis controlled?
at the level of acetyl-CoA carboxylase
42
what is the "general pathway" for storage of synthesized fatty acids as triglycerides?
- glycerol-3-P + acyl-CoA = - lysophosphatidic acid + acyl-CoA = - phosphatidic acid - PO4 = - 1,2-DAG + acyl-CoA = - TAG
43
what tissues will use the "general pathway"?
liver and adipocytes
44
what is the source of glycerol-3-P?
synthesized from glucose via glycolysis steps | glucose --> DHAP --> G3P
45
what is unique of TAG synthesis in the small intestine?
small intestine will re-aceylate 2-MAG
46
differences between b-oxidation and FA synthesis: location
b-oxidation: mitochondria | FA synthesis: cytosol
47
differences between b-oxidation and FA synthesis: group carrier
b-oxidation: CoA | FA synthesis: ACP
48
differences between b-oxidation and FA synthesis: electron donor/acceptor
b-oxidation: FAD, NADH | FA synthesis: NADPH
49
differences between b-oxidation and FA synthesis: unit product/donor
b-oxidation: Acetyl-CoA | FA synthesis: Malonyl-CoA