Complex Lipid Synthesis

Pre-Activity

1. Compare and contrast tryacylglycerols, glycerophospholipids, and Sphinolipids

    

   a. Look at overall structure

   b. Look at individual components

   c. Look at chemical properties

2. Using your analysis from Q1 , identify the main differences between the molecular groups above

   a. Triacylglycerols and glycerophospholipids

   b. Triacylglycerols and sphinogolipids

   c. Glycerophospholipids and sphinogolipids

Triglyceride

https://en.wikipedia.org/wiki/Triglyceride

Glycerophospholipids

https://en.wikipedia.org/wiki/Glycerophospholipid

Sphinolipids

https://en.wikipedia.org/wiki/Sphingolipid

Activity

Triacylglycerols

1. As you undoubtedly know the backbone to a triacylglycerol is glycerol, however you might not be aware that the precursor needed is actually Glycerol-3-phosphate.

1.A. How is glycerol-3-phosphate made using glycerol?

1.B. How is glycerol-3-phosphate made using intermediates in central metabolism? What metabolic pathway is this similar to? How is it different?

https://en.wikipedia.org/wiki/Glycerol_3-phosphate

1.C. Which method is used in adipocytes and why?

2. Now that we have Glycerol-3-phosphate, two fatty acids are added via esterification reactions.

2.A. What class of lipids are generated in this step?

https://en.wikipedia.org/wiki/Phosphatidic_acid

2.B. Are the fatty acids activated? How do you know?

3. Phosphatidic acids have two fatty acid chains, but triacylglycerols have three. What remaining steps must take place in order for triacylglycerol synthesis to be completed?

Glycerophospholipids

4. Similar to triacylglycerols, the glycerophospholipids use phosphatidic acid as a precursor, indeed phosphatidic acids are glycerophospholipids themselves.

4.A. What are the six main phospholipid classes found in our membranes?

https://en.wikipedia.org/wiki/Membrane_lipid#Major_classes

• Phospholipids
• Glycolipids
• Fatty Acids
• Phosphoglycerides
• Sphinogolipids
• Sterols

4.B. How are these classes similar and different from phosphatidic acids?

5. In order to modify the phosphate group on the phospholipid it must first be activated.

5.A. How is the phosphatidic acid activated?

5.B. Where does the molecule join the phosphatidic acid?

• On the phosphate

6. In order to make PI what molecule must be added to CDP-diacylglycerol and where?

$$\ce{Posphatidic Acid + CTP ->[][CDP-diacylglycerol synthase] PP_i + CDP-diacylglycerol}$$

7. In order to make PS, PE and PC a serine is joined to the CDP-diacylglycerol

7.A. Compare the structures of phosphatidylserine and phosphatidylethanolamine, how could one be converted to the other?

• Carboxylate alpha carbon

7.B. Compare the structures of PE and PC. What are the differences?

• Choline is all methylated
• Phosphatidylcholine can also be produced by three successive methylations of phosphatidyl-ethanolamine
• The methyl group donor in this pathway is an activated derivative of methionine, S-adenosyl-l-methionine (AdoMet).

7.C. To make PG and CL a glycerol-3-phophate is added to the CDP-diacylglycerol. Compare cardiolipin and PG. What is added to PG to make CL?

https://en.wikipedia.org/wiki/Cardiolipin

https://www.easybiologyclass.com/biochemistry-membrane-lipids-properties-structure-classification/

Sphinoglopids

8. What are the two molecules needed to make sphingosine? How is this different from triacylglycerol and phospholipid synthesis?

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9. What must be added to sphingosine (and where) in order to make a ceramide? Is this an esterification reaction?

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10. What happens to the palmitoyl fatty acid to make ceramide?

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11. What is added to a ceramide to make sphingomyelin? What other group of lipids is this similar to?

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12. Cerebroside is in the class of lipids called glycosphingolipids. What molecules must be added to ceramide to make this class of lipids?

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