8 - Lipids and cholesterol Flashcards

1
Q

What is the main type of lipid involved in cellular membranes?

A

Glycerophospholipids - phospholipids with an additional small molecule attached to the phosphate.

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2
Q

What are 4 examples of cellular glycerophospholipids and their functions?

A

Phosphatidylinositol - precursor of signalling molecules.

Phosphatidylserine - A key ‘‘eat me “ signal in apoptosis.

Phosphatidylcholine - Structural component of membranes.

Phosphatidylethanolamine - Donor of functional groups to some membrane anchored proteins, structural roles, regulates curvature.

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3
Q

What are 3 properties of lipids?

A

Lipids are amphipathic meaning they have a hydrophobic (non-polar) end and a hydrophilic (polar ) end.

Membranes made by lipids are fluid.

Lipids can produce signalling molecules.

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4
Q

What is an example of a lipid signalling molecule and how does it work?

A

Ptdins has an inositol ring which can be phosphorylated by kinases:

Ptdins -> Ptdins 4P -> Ptdins(4,5)P2

Certain signals catalyse the breakdown of Ptdins(4,5)P2 into inositol trisphosphate and diacylglycerol both of which are key intracellular messengers.

Ptdins(4,5)P2 -> DAG + IP3

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5
Q

Where does GPL biosynthesis occur, what molecule are GPL’s synthesised from and how does the process take place?

A

GPL biosynthesis occurs within the ER.

The molecule used to synthesise GPL’s is phosphatidate.

Phosphatidate’s conversion into diacylglycerol (DAG) is catalysed by phosphatidic acid phosphatase (PAP).

DAG can then react with an activated alcohol to form phospholipids or with acyl CoA to form triglycerides.

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6
Q

What is an example of a disease involving glycerophospholipids, who is often affected and how is it treated?

A

PC is a major component of lung surfactant, maintaining surface tension of fluid to keep alveoli open.

Low PC (due to lack of dipalmitoyl phosphatidylcholine biosynthesis ) results in collapse of alveoli - respiratory distress syndrome.

Often affects premature babies causing laboured breathing, blue fingers / toes.

Treated with ventilation (O2) and artificial surfactant.

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7
Q

What is sphingomyelin’s 2 main roles?

A

Sphingomyelin:
- Major structural component of membranes (lipid rafts)
- Source of messenger molecules (ceramide and sphingosine-1-phosphate).

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8
Q

How is sphingomyelin synthesised and what enzyme catalyses the synthesis?

A

Ceramide + Phosphatidylcholine -> Sphingomyelin + DAG.

Reaction catalysed by sphingomyelin synthase.

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9
Q

How are gangliosides synthesised and what is their role?

A

Gangliosides are sphingolipids that have been modified by the addition of sugars.

Gangliosides are important cell surface molecules that are highly prevalent in nervous tissue.

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10
Q

What is an example of a disease involving gangliosides?

A

Tay Sachs disease: inherited disorder affecting motor function and vision - fatal by 3 years, can be diagnosed during pregnancy no treatment available.

Patient is unable to degrade gangliosides (happens in lysosomes), lysosomes (particularly in neurons) fill with gangliosides.

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11
Q

What role does sphingosine play in the body?

A

Sphingosine is phosphorylated by sphingosine kinase to generate sphingosine-1-phosphate - a key signalling molecule

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12
Q

What are 3 characteristics of cholesterol?

A

Helps maintain membrane bilayer integrity and regulates permeability.

Precursor of steroids, vitamins and bile salts

Excess cholesterol is associated with cardiovascular disease

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13
Q

What is the first step in cholesterol biosynthesis?

A
  1. Synthesis of isopentenyl pyrophosphate (via mevalonate)
  • Acetoacetyl CoA + Acetyl CoA + H2O -> HMG-CoA + CoA
  • HMG-CoA reductase converts HMG into mevalonate.
  • Mevalonate is converted into a 5-carbon unit: 3-isopentenyl pyrophosphate.
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14
Q

What is the second step of cholesterol synthesis?

A
  1. Condensation of six molecules of isopentenyl pyrophosphate to form squalene
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15
Q

What is the third and final step of cholesterol biosynthesis?

A
  1. Cyclisation of squalene to lanosterol which is then processed forming cholesterol.
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16
Q

Where is cholesterol synthesised and how is cholesterol biosynthesis regulated?

A

Cholesterol is synthesised in the liver and the intestines

Rate of cholesterol synthesis is responsive to how much cellular cholesterol is present.

Regulated by HMG-CoA reductase (integral membrane protein in ER).

17
Q

In what 4 ways is HMG-CoA reductase controlled?

A
  1. Rate of synthesis of HMG-CoA reductase mRNA.
  2. Rate of translation of HMG-CoA reductase mRNA to protein.
  3. Rate of degradation of HMG-CoA reductase protein.
  4. Phosphorylation state of HMG-CoA reductase protein.
18
Q

How does transcriptional regulation of HMG-CoA reductase work?

A

SREBP (Sterol regulatory element binding factor) - transcription factor.

SRE - the region of the HMG-CoA reductase that SREBP binds to, regulating the transcription of HMG-CoA reductase.

19
Q

How does the translational regulation of HMG-CoA reductase work?

A

The translation of HMG-CoA reductase mRNA to protein is inhibited by nonsterol metabolites derived from mevalonate.

20
Q

How does degradation regulation of HMG-CoA reductase work?

A

HMG-CoA reductase membrane domain senses increasing levels of sterols, then
Interacts indirectly with ubiquitinating enzymes.

HMG-CoA reductase becomes polyubiquitinated and is extracted from the membrane and then degraded by the proteasome

21
Q

How does phosphorylation regulation of HMG-CoA reductase work?

A

Phosphorylation is by AMP-activated protein kinase.

Phosphorylation of HMG-CoA reductase stops cholesterol synthesis.

22
Q

How is cholesterol transported around the body?

A

Cholesterol is transported in body fluids in lipoprotein particles.

23
Q

What is the structure of a lipoprotein particle and what are the 2 types?

A

lipoprotein particles have a hydrophobic lipid core, surrounded by polar lipids and proteins.

  • HDL: high density lipoprotein (Good cholesterol)
  • LDL: low density lipoprotein (Bad cholesterol)
24
Q

What do bile salts do, where are they synthesised, stored and released?

A

Bile salts solubilise dietary lipids.

Synthesised in the liver.

Stored in the gallbladder.

Released into the small intestine.

25
Q

What are the 5 classes of steroid hormones?

A

Progestogens.

Glucocorticoids.

Mineralocorticoids.

Androgens.

Oestrogens.

26
Q

How is vitamin D synthesised, what does it become and what is the role of this product?

A

7-dehydrocholesterol becomes previtamin D3 when exposed to UV light and then vitamin D3.

Vitamin D3 is converted into calcitriol which binds to a specific protein that regulates transcription.

27
Q

What are statins and what are they used to treat?

A

Statins are HMG-CoA reductase inhibitors - drugs used to reduce cholesterol.

Statins are prescribed for those at risk of coronary heart disease.