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Biochemistry 2 > Lipid biosynthesis > Flashcards

Lipid biosynthesis Flashcards

1
Q

Functions of lipids

A

Energy storage (TG)

Constituents of membranes

Anchors for membrane proteins (IP2/IP3)

Cofactors for enzymes (Vit K)

Signaling molecules (eicosanoids, IP3)

Pigments (retinal)

Detergents (bile salt)

Transporters

Antioxidants (Vit A)

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2
Q

What is the first step of fatty acids biosynthesis

A

Formation of Malonyl-CoA from acetyl-CoA

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3
Q

the enzyme responsible for conversion of acetyl-CoA to Malonyl-CoA

A

Acetyl-CoA Carboxylase (ACC)

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4
Q

Three important domains in ACC

A

Biotin carboxylase
Transcarboxylase
Biotin carrier protein

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5
Q

How the conversion of acetyl-CoA with ACC happens

A

Biotin carrier protein has an arm. It is used to capture bicarbonate and transfer to acetyl-CoA

Biotin carboxylase portion of ACC with the use of ATP adds CO2 to biotin carrier protein arm

Once it is carboxylated, biotin carrier protein shifts 180 degrees to transcarboxylase arm. At transcarboxylase arm there is also a docking mechanisms for acetyl-CoA

Addition of CO2 to acetyl-CoA= malonyl-CoA

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6
Q

What enzyme takes malonyl and converts to FAs

A

Fatty Acid Synthase (does not use ATP)

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7
Q

What is particular about Fatty Acid synthase

A

It consists of 6 enzymes
AND

Functions as dimer

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8
Q

2 types of Fatty acid Synthase and where it can be found

A

Type I in vertebrates and fungi

Type II in bacteria and plant

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9
Q

How many FAs are synthesized a time by Fatty Acid synthase dimer

A

2

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10
Q

What is the first requirement for synthesis of FAs with FAS and what happens with it

A

Acetyl-CoA not activated

It is captured by KS domain of the synthase

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11
Q

What is ACP domain and what does it do

A

Acyl carrier protein

It gets malonyl-CoA with the help of MAT domain

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12
Q

What happens after malonyl-CoA is attached

A

With that the carboxyl group of malonyl co a, it interacts with acetyl coa, the result is malonyl coa adds two more carbons to itself-> grow of the chain

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13
Q

Why ACP is an important domain

A

It is where the chain grows and receives malonyl-CoA

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14
Q

What happens after acetyl-CoA is added to malonyl-CoA

A

We need to get rid of double bonds and oxygen, so there is reduction happening and hydrogen is added

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15
Q

After the reduction of the chain occurs, what happens

A

The chain is transferred to KS domain, so ACP is ready to receive new malonyl-CoA

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16
Q

Each cycle FAS adds how many carbon to the chain and what is the limit

A

Adds 2 carbons

Until 16 carbons are reached (palmitate) after than new enzymes are needed

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17
Q

Most common FAs synthesized

A

Palmitate

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18
Q

Long chain FA are produced in

A

ER or in mitochondria

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19
Q

Palmitate is synthesized in

A

Cytoplasm

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20
Q

Two saturated FAs that synthesized

A

Palmitate (16:0)

Stearate (18:0)

21
Q

What FAs can come from palmitate and stearate

A

Palmioleate (16:1)

Oleate (18:1)
Double bond at C9-10

22
Q

What is needed to synthesize palmioleate and oleate

A

Fatty acyl-CoA desaturase by oxidative reactions

23
Q

What is the issue of linoleate

A

It is (18:2 delta 9,12)

As it has 2 double bonds they cannot be synthesized in mammals-> essential

24
Q

What is synthesized from linoleate

A

Arachidonate (20: delta 5,8,11,14)

25
Q

Can mammals synthesize arachidonate

A

Yes, if linoleate is available

26
Q

What are sources of acetyl-CoA how it is regulated and thus biosynthesis of FAs is regulated

A

From pyruvate->Puryvate decarboxylation (cytoplasm)

AA catabolism in
mitochondria

27
Q

If AAs catabolism happens inside mitochondria, so how acetyl-CoA is delivered to cytoplasm

A

Acetyl-CoA+oxaloacetate->citrate with citrate synthase

Now citrate can be transported out of mitochondria because there are mitochondrial transporters in the mitochondrial wall

In cytoplasm: citrate lyase breaks down citrate to acetyl-CoA and oxaloacetate .

28
Q

What happens when citrate is broken down in the cytoplasm

A

Oxaloacetate is needed to be sent back in mitochondria.

Two options:
1)Conversion to malate with malate dehydrogenase and then malate is transported through malate-alpha ketoglutarate transporter

2)OR malate can be converted to pyruvate by malic enzyme in the cytoplasm-> pyruvate transported into the mitochodria

29
Q

What are other way to regulate biosynthesis of FAs except acetyl-CoA concetration

A

Acetyl-CoA carboxylase is the limiting enzyme

It is inhibited by phosphorylation by epinephrine and glucagon signal (PKA pathway)

Palmitoyl-CoA ( the end product) inhibit ACC -> negative feedback

Citrate accumulation in mitochondria results in activation of ACC

30
Q

Catabolism of FAs
Produces ___
Take place in ___

A

Produces acetyl-CoA
Produces electron donors (FADH2 and NADH)
-Takes place in the mitochondria

31
Q

Anabolism of FAs
requires ___
Takes place in ___

A

Requires acetyl-CoA and malonyl-CoA

Requires electron donor NADPH (as hydrogen donor)

Takes place in cytosol in animals

32
Q

Insulin and FA synthesis relationship

A

Insulin promotes FA synthesis

33
Q

How ACC is regulated

A

When it is phosphorylated it is inactive

When dietary carbohydrate coming-> a lot of carbohydrate-> high insulin leading to activation of phosphatase->dephopshorylation -> acetyl CoA to malonyl-CoA

Low glucose leads to glucagon-> GPCR-> PKA->phosphorylated ACC-> inactivation

34
Q

What happens when there is accumulation of malanyl-CoA

A

Cells are in energy sufficiency situation.

Malanyl inhibits carnitine acyl transferase-1 that transfers FA in mitochondria -> inhibition of beta-oxidation-> less energy

35
Q

The most common store form of FAs

A

TGs

36
Q

from where we can get glycerol?

A

Glycolysis or release from TG metabolism

37
Q

How glycerol is converted to phosphatidic acid

A

1) Glycerol is converted to G3P

2) Acyl transferase that takes 2 Fatty acyls and attached to G3P->phosphatidic acid ( 2 FAs and phosphate group)

38
Q

What happens to phosphatidic acid

A

1) attachment of head group and thus -> glycerophospholipid-> membrane
2) or with phosphatidic acid is dephosphorylated to 1,2-Diacylglycerol , where third carbon is free, with phosphatidic acid phosphatase. So acyl transferase attaches another FAs->TGs

39
Q

What hormone promotes synthesis of TG

A

Insulin

40
Q

Cholesterol is

A

Structure membrane and precursor for signaling molecules

41
Q

How do we synthesize cholesterol

A

Acetate -> HMG-CoA with HMG-CoA synthase

HMG-CoA to Mevalonate with HMG-CoA reductase

And then phosphorylated, polymerized and cyclized to cholesterol

42
Q

Biosynthesis of cholesterol occurs in

A

Cytoplasm/ microsomes

43
Q

What step in cholesterol synthesize can be regulated

A

HMG-CoA reductase

44
Q

AMP-dependent protein kinase and cholesterol synthesize

A

When AMP rises (low energy situation), AMPK phosphorylates the enzyme-> reduced activity -> reduced cholesterol synthesize

So acetate and FAs are used for energy rather than cholesterol synthsize

45
Q

Glucagon and epinephrine and cholesterol synthesize

A

Glucagon-> low energy

Leads to PKA pathway-> phosphorylation-> reduced activity of HMG-CoA reductase

46
Q

Insulin and HMG-CoA reductase

A

Cascades leading to dephosphorylation-> increased activity

47
Q

What does Insig do

A

Insulin-induced gene protein senses cholesterol levels. and triggers ubiquination of HMG-CoA reductase-> limited cholesterol synthesize

48
Q

What is SREBPs and what do they do

A

Transcriptional factors

Sterol Regulatory Element Binding proteins activate HMG-CoA reductase by inducing its transcription

49
Q

What are statins or lipitor

A

Drugs that inhibits HMG-CoA reductase -> to treat high cholesterol

Biochemistry 2 (17 decks)

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