BMS 100 Cell Membrane and Cytoskeleton Lecture Notes 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 fo...

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