8 - Lipids and cholesterol Flashcards
What is the main type of lipid involved in cellular membranes?
Glycerophospholipids - phospholipids with an additional small molecule attached to the phosphate.
What are 4 examples of cellular glycerophospholipids and their functions?
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.
What are 3 properties of lipids?
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.
What is an example of a lipid signalling molecule and how does it work?
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
Where does GPL biosynthesis occur, what molecule are GPL’s synthesised from and how does the process take place?
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.
What is an example of a disease involving glycerophospholipids, who is often affected and how is it treated?
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.
What is sphingomyelin’s 2 main roles?
Sphingomyelin:
- Major structural component of membranes (lipid rafts)
- Source of messenger molecules (ceramide and sphingosine-1-phosphate).
How is sphingomyelin synthesised and what enzyme catalyses the synthesis?
Ceramide + Phosphatidylcholine -> Sphingomyelin + DAG.
Reaction catalysed by sphingomyelin synthase.
How are gangliosides synthesised and what is their role?
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.
What is an example of a disease involving gangliosides?
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.
What role does sphingosine play in the body?
Sphingosine is phosphorylated by sphingosine kinase to generate sphingosine-1-phosphate - a key signalling molecule
What are 3 characteristics of cholesterol?
Helps maintain membrane bilayer integrity and regulates permeability.
Precursor of steroids, vitamins and bile salts
Excess cholesterol is associated with cardiovascular disease
What is the first step in cholesterol biosynthesis?
- 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.
What is the second step of cholesterol synthesis?
- Condensation of six molecules of isopentenyl pyrophosphate to form squalene
What is the third and final step of cholesterol biosynthesis?
- Cyclisation of squalene to lanosterol which is then processed forming cholesterol.
