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BIOCHEM > Final Lipid cholesterol biosynthesis > Flashcards

Final Lipid cholesterol biosynthesis Flashcards

1
Q

What is phosphatidate and where does its synthesis take place

A

precursor for triacylglycerols liver and phospholipids found in ER

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2
Q

Phosphatidate can lead to the production of Triacylglycerol, tell me the process?

A
  1. Phosphatidate is formed by the addition of two fatty acids to glycerol 3-phosphate
  2. Phosphatidate is first hydrolyzed to give diacylglycerol (DAG),
  3. which is then acylated to a triacylglycerol
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3
Q

Where does phospholipid synthesis take place?

A

endoplasmic reticulum

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4
Q

The synthesis of triacylglycerol is completed by what complex that is bound to the ER membrane

A

triacylglycerol synthetase complex

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5
Q

Phospholipid synthesis, which takes place in the endoplasmic reticulum, requires the combination of

A

diacylglycerol with an alcohol for one or the other components to be activated

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6
Q

The activated phosphatidyl unit then reacts with the hydroxyl group of an alcohol called inositol&raquo_space;>what are the products?

A

phosphatidylinositol and cytidine monophosphate (CMP)

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7
Q

Subsequent phosphorylations of phosphatidylinositol catalyzed by specific kinases lead to the synthesis of

A

phosphatidylinositol 4,5-bisphosphate, a membrane lipid that is also an important molecule in signal transduction

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8
Q

what happens when activated phosphatidyl unit reacts with the alcohol phosphatidylglycerol?

A
  1. products are diphosphatidylglycerol (cardiolipin) and CMP.
    2a. For example, it is required for the full activity of cytochrome c oxidase (complex IV).
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9
Q

Cardiolipin plays an important role in the ….

A

organization of the protein components of oxidative phosphorylation

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10
Q

ethanolamine is phosphorylated by ATP to form the precursor, phosphorylethanolamine. This precursor then reacts with CTP to form the activated alcohol, CDP-ethanolamine. The phosphorylethanolamine unit of CDP-ethanolamine is subsequently transferred to a diacylglycerol to form phosphatidylethanolamine, this is an example of

A

alcohol being activated by phosphorylation and subsequent reaction with CTP to form CDP-alcohol.
The activated alcohol reacts with diacylglycerol to form the phospholipid

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11
Q

Sphingolipids are synthesized from what and found in where?

A

ceramide
plasma membrane in all eukaryotes

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12
Q

Ceramide is the starting point for the formation of

A

sphingomyelin and gangliosides.

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13
Q

How is phospatidate formed?

A

the addition of two fatty acids to glycerol 3-phosphate

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14
Q

Tell me how phosphatidate formed aka the steps

A
  1. glycerol 3-phosphate is first acylated by a saturated acyl CoA to form lysophosphatidate,
  2. commonly acylated by unsaturated acyl CoA to yield phosphatidate
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15
Q

In some cases, diacylglycerol is activated by forming

A

cytidine diphosphodiacylglycerol (CDP- diacylglycerol

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16
Q

In triacylglycerol biosynthesis, the product is a hydrophobic molecule but for Phospholipid synthesis the molecule is?

A

Amphiphatic

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17
Q

What enzyme catalyzes the conversion of phosphatidate to diacylglycerol

A

Phosphatidic acid phosphatase (PAP)

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18
Q

when PAP activity is high, phosphatidate is ….

A

phosphatidate is dephosphorylated and diacylglycerol is produced

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19
Q

When PAP activity is lower, Phosphatidate is …

A

used as a precursor for different phospholipids, such as phosphatidylinositol and cardiolipin

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20
Q

In a way how is Phosphatidate unique?

A
  1. signal molecule itself
  2. regulates the growth of ER and nuclear membrane
  3. acts as a cofactor that stimulates gene expression
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21
Q

What are the signal molecules that enhance the activity of PAP?

A

CDP-diacylglycerol, phosphatidylinositol, and cardiolipin

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22
Q

What are the signal molecules that inhibit the activity of PAP?

A

sphingosine and dihydrosphingosine

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23
Q

If there was an ihibition/loss in PAP function what would that mean for normal adipose tissue development?

A
  1. The loss of PAP function prevents normal adipose-tissue development, leading to lipodystrophy (severe loss of body fat) and insulin resistance
  2. would also mean it would be hard to store energy and produce energy for muscles.
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24
Q

Excess PAP can lead to what condition and why

A

obesity- b/c the PAP would lead to more production of triacylglycerol thus more stored in adipose tissue

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25
Q

Cholesterol is vital in the body, how

A

fluidity of animal cell membranes and is the precursor of steroid hormones such as progesterone, testosterone, estradiol, and cortisol

26
Q

Where is cholesterol synthesized

A

in the liver

27
Q

Cholesterol is synthesized in the liver from what molecule

A

acetyl CoA in 3 stages

28
Q

The rate of cholesterol synthesis is lowly responsive to the cellular level of cholesterol? T or False

A

False

29
Q

All 27 carbon atoms of cholesterol are derived from acetyl CoA in a three-stage synthetic process but what are the locations

A

stage 1 in Cytoplasm
Stage 2&3 in ER lumen

30
Q

what occurs in the stage one of cholesterol synthesis

A

is the synthesis of isopentenyl pyrophosphate, an activated isoprene unit that is the key building block of cholesterol

31
Q

What happens in stage 2&3 of cholesterol biosynthesis?

A

Stage 2: is the condensation of six molecules of isopentenyl pyrophosphate to form squalene Stage 3: squalene cyclizes and the tetracyclic product is subsequently converted into cholesterol

32
Q

The committed step of in cholesterol synthesis is ?

A

HMG CoA is then transformed into mevalonate

33
Q

acetyl CoA and acetoacetyl CoA are combined to form ?

A

HMG CoA

34
Q

What catalyzes the reaction of HMG CoA to mevalonate?

A

HMG CoA reductase and driven by 2 NADPH

35
Q

How is cholesterol synthesis in relation to ketone body formation?

A

HMG is the intermediate in ketone body formation

36
Q

How can HMG CoA reductase be inhibited?

A

class of molecules called statins

37
Q

which part in stage one of cholesterol synthesis is high demanding in ATP?

A

when Mevalonate is converted into 3-isopentenyl pyrophosphate

38
Q

Are you going to run cholesterol with low levels of energy?

A

No, because it is linked to the energy of the cell.
stage one requires 3 ATP molecules

39
Q

Six molecules of isopentenyl pyrophosphate condense to form squalene by the following sequence:

A

C5->C10->C15->C30

40
Q

In gluconeogenesis we have seen that 3 carbon molecules have come together to become glucose 3,6- biphosphate, where do we see this in cholesterol synthesis?

A

two isomeric forms of isopentenyl pyrophosphate to form dimethylallyl pyrophosphate

41
Q

Which stage in cholesterol is more demanding in energy?

A

stage one
stage two is driven by hydrolysis and reduction by NADPH

42
Q

In the final step what intermediate is used to produce the final product of Cholesterol?

A

Squalene

42
Q

How do we regulate cholesterol biosynthesis?

A

mediated by the cellular levels of cholesterol and in the amount/activity of HMG- CoA reductase

43
Q

sterol regulatory element-binding protein (SREBP) Controls what process?

A

The rate of synthesis of HMG-CoA reductase mRNA

44
Q

SCAP and SREBP stay in the endoplasmic reticulum in response to levels of what?

A

When levels of cholesterol are elevated

45
Q

When the level of cholesterol begins to fall, where is the SCAP and SREBP located?

A

golgi

46
Q

cholesterol level has fallen, what is the feedback regulation?

A

SCAP escorts SREBP to the Golgi complex, where it is proteolytically processed and activated. The activated SREBP moves to the nucleus to simulate reductase mRNA synthesis.

47
Q

when level are low in cholesterol how is ti possible to disassociate SREBP from SCAP

A

Serine protease cleaves inside the lumen of Golgi, and then SREBP moves along the membrane to be cleaved by metalloprotease. thus releasing the DNA binding domain into cytoplasm.

48
Q

we know that cholesterol levels can take part in the regulation of cholesterol but what other ways ti can be regulated?

A
  1. rate of translation of the reductase mRNA - controlled by diet cholesterol and metabolites of mevalonate
  2. Increases in cholesterol concentration result in the proteolytic degradation of the reductase.
  3. Phosphorylation of the reductase by AMP- dependent kinase inactivates the enzyme
49
Q

why does cholesterol synthesis cease when ATP levels are low?

A

To make cholesterol it is very demanding in energy

50
Q

How are we able to transport cholesterol?

A

Lipoproteins transport cholesterol and triacylglycerols in the organism

51
Q

The protein components of lipoproteins (called apoproteins) have two roles:

A

(1) solubilize the lipids
(2) direct the particles to specific targets

52
Q

The greater proportion of lipid, the less dense the particle true or false

A

true

53
Q

Low-density lipoprotein (LDL) is the major carrier of cholesterol in the blood true or false

A

true

54
Q

LDL carries cholesterol released into the blood back to the liver, a process called reverse cholesterol transport true or false?

A

false its High-density lipoprotein (HDL

55
Q

What are VLDL and purpose?

A

very low density protien, it used for Triacylglycerols and cholesterol over the liver’s own needs are exported into the blood

56
Q

in what form is cholesterol transferred into peripheral tissue?

A

LDL

57
Q

HDL is transferred from what type of tissue and what is the process sometimes called?

A

liver; reverse cholesterol transport

58
Q

to form
squalene what transformation is involved?

A

in Stage 2 it involves the transformation of 6 isopentenyl pyrophosphate molecules

59
Q

Cholesterol synthesis is regulated in the liver and LDL is normally removed from the blood in a process called

A

receptor-mediated endocytosis

60
Q

What is the mechanism of transport for cholesterol into cell?

A
  1. Apoprotein B-100 in LDL binds to the LDL-receptor on the cell surface.
  2. The receptor-LDL complex is internalized, a process called endocytosis.
  3. The LDL is hydrolyzed in lysosomes, whereas the LDL receptor is returned to the cell surface to bind another LDL particle.
61
Q

Cholesterol is used as a precursor for what Hormone and synthesis of what type of molecules?

A

steroids and bile salts and vitamins

BIOCHEM (5 decks)

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