BMS100_Ph1-20-W23_Cell membrane post-learning 1_Phospholipids.pdf

Lecture : Cell membrane and cytoskeleton Post-learning 1: Phospholipids Dr. Rhea Hurnik BMS 100 Learning Outcomes Classify phospholipids as belonging to either fatty acid or isoprenoid structural group List the 3 main components of a phospholipid Name the 3 most common phosphoglycerides found in the...

Lecture : Cell membrane and cytoskeleton Post-learning 1: Phospholipids Dr. Rhea Hurnik BMS 100 Learning Outcomes Classify phospholipids as belonging to either fatty acid or isoprenoid structural group List the 3 main components of a phospholipid Name the 3 most common phosphoglycerides found in the cell membrane. Describe the cellular location and basic steps of phospholipid synthesis and outline the role of the transfer molecule, CDP Explain how phospholipids synthesized in the smooth ER reach the plasma membrane Lipid introduction Lipids can be broken down structurally into two main classes: § 1) Those based on fatty acid structure § 2) Those based on isoprenoid structure Fatty acids Fatty acids can form of number of derivatives, including phospholipids § Phospholipids have three components: Hydrocarbon chain Backbone § Glycerol Phosphoglycerides § Ceramide Sphingomyelin Phosphate-alcohol head group Phosphoglycerides Phospholipids with a glycerol backbone § If both fatty acids are linked to the glycerol backbone with an ester link, it is called a phosphatidate § If one fatty acids is linked to the glycerol backbone with an ester link while the other has an ether link, it is called a plasmalogen § Both can be found in the cell membrane, but phosphatidates are much more common Phosphatidates The basic structure of a phospholipid is phosphatidic acid H § Looking at the structure of phosphatidic acid, why do you suppose we call it a “phosphatealcohol head group” Phosphatidic acid Phospholipids in the cell membrane Let’s take a look at the three most common phosphoglycerides in the cell membrane: § Phosphatidylethanolamine § Phosphatidylserine § Phosphatidylcholine Phospholipids in the cell membrane Phosphatidylethanolamine Phospholipids in the cell membrane Phosphatidylserine Phospholipids in the cell membrane Phosphatidylcholine Sphingomyelin Sphingomyelin is another common phospholipid found in the cell membrane § Contains a ceramide backbone Can also be classified as a sphingolipid Check your knowledge What are the components of a glycerophospholipid? § 2 Hydrocarbon chains, glycerol, phosphate-alcohol head group § 3 Hydrocarbon chains, glycerol, phosphate-alcohol head group § 2 Hydrocarbon chains, ceramide backbone, phosphatealcohol head group § 3 Hydrocarbon chains, ceramide backbone, phosphatealcohol head group Phospholipid synthesis Phospholipid synthesis occurs primarily on the luminal surface of the smooth ER and the inner mitochondrial membrane § We will will only be discussing the synthesis of glycerophospholipids § Basic steps § 1. Synthesis of glycerol backbone § 2. Attachment of fatty acids to backbone via ester linkage § 3. Addition of head group § 4. Exchange/modification of head group First two steps are shared with triacylglycerol synthesis Phospholipid synthesis – 1 & 2 Steps 1 & 2 § Starting molecule, glycerol-3-phosphate can be derived from: Addition of phosphate group to glycerol § Only occurs in the liver Conversion of glycerol-3-phosphate from dihydroxyacetone phosphate (DHAP) § DHAP is an intermediate from which catabolic pathway? Phospholipid synthesis – 1 & 2 Step 1 & 2 H § Two fatty acyl CoAs are added to glycerol-3-phosphate forming phosphatidic acid § Often, but not always, the fatty acid at C-1 is saturated and the fatty acid and C-2 is unsaturated Phosphatidic acid Phospholipid synthesis – 3 Step 3: Addition of head group § One of the hydroxl is first activated by attachment of a nucleotide, cytosine diphosphate (CDP) Phospholipid synthesis – 3 Step 3: Addition of head group § CMP is displaced via nucleophilic attack and replaced by a head group Phospholipid synthesis – 3 Step 3: Addition of head group § Let’s take a look at an example Phospholipid synthesis – 3 Step 3: Addition of head group § Another possibility utilized by eukaryotes is the addition of CDP-headgroup to diacylglycerol Phospholipid synthesis – 3 Step 3: Addition of head group § Let’s take a look at an example Phospholipid synthesis – 4 Step 4: Modification or alteration of headgroup § Phosphatidylserine and phosphatidylethanolamine can be interconverted in a reversible head-group exchange reaction Phospholipid synthesis – 4 Step 4: Modification or alteration of headgroup § Phosphatidylethanolamine can be converted to phosphatidylcholine by addition of 3 methyl groups Methyl groups are donated by S-adenosylmethionine (SAM) a common methyl donor § Denotated as adoMet Phosphatidylinositol Phosphatidylinositol is a less common phospholipid in the cell membrane, but it plays an important role in cell signalling § More to come later! Phospholipids, next steps Now we need to get some newly made phospholipids to the other side of the sER membrane and to the cell membrane § Will they spontaneously flip over to the luminal side? Phospholipids, next steps Now we need to get some newly made phospholipids to the other side of the ER membrane and to the cell membrane § Will they spontaneously flip over to the luminal side? NO! Require a special enzymes, flippase, to translocate phospholipids across the ER membrane to the cytosolic side § Pieces of sER membrane contain the new phospholipids bud off as little vesicles and are insert into the plasma membrane Check your knowledge What nucleotide is used help with the addition of head group to phosphatidic acid? § A) Cytosine § B) Guanine § C) Adenine § D) Thymine End References Alberts et al. Molecular Biology of the Cell. Garland Science. Betts et al. Anatomy and Physiology (2ed). OpenStax Lehninger Principles of Biochemistry 4th ed. Figure 21-36. Page 818