18.1: Phospholipids and Sphingolipids: Synthesis and Intracellular Movement

• Fatty acids are composed of:

  • Phospholipids

  • Sphingolipids

  • Triglycerides

• The synthesizing of fatty acids occurs through water-soluble enzymes which are modified through the endoplasmic reticulum

• The synthesizing final steps are catalyzed by membrane associations in the ER, Golgi, mitochondria, and peroxisomes

• Pre-existing membranes have each type of membrane initially incorporated into it

• The exoplasmic and cytosolic leaflets distribute membrane phospholipids

18.2: Cholesterol: A Multifunctional Membrane Lipid

• The cytosol is the main base for the initial steps in cholesterol biosynthesis, and the last steps take place in the ER membrane

• HMG-CoA reductase catalyzes the rate-controlling step required for cholesterol biosynthesis

• HMG-CoA has transmembrane segments embedded into the ER

• The biosynthetic precursors of steroid hormones are intermediated by cholesterol and isoprenoid, and lipid-soluble vitamins, bioactive molecules, and bile acids also helped

• There is evidence that indicates that cholesterol and phospholipid membrane movement is not highly dependent on the Golgi complex

• Systems that help with cholesterol and phospholipid transport:

  • Golgi independent vesicular transport

  • Direct protein-mediated contacts that travel between different membranes

  • Soluble protein carriers

• StAR proteins move cholesterol through the mitochondria for the function of steroid hormone synthesis

• StAR proteins have a hydrophobic cholesterol building pocket

• NPC1 is needed for cholesterol to move normally into intracellular compartments

18.3: Lipid Movement into and out of Cells

• Proteins needed for lipid movement in and out of cells

• Cell surface transport proteins and water-soluble binding proteins; or

• Lipoprotein secretion and lipoprotein receptor facilitated uptake

• Fatty acids are transported in the plasma membrane through fatty acid transporters such as FATPs and CD36, and these fatty acids are moved between intracellular binding proteins and extracellular carriers

• The ABC superfamily, which is made of ATP hydrolyzing small molecule pumps, controls ABC proteins which control the export of lipids in the cells

• Lipids in lipoprotein cores:

  • Cholesterol

  • Esters

  • Triglycerides

• Lipoproteins all have a unique characteristic protein and a different function in the cellular export system

18.4: Feedback Regulation of Cellular Lipid Metabolism

• Enzymes, transporters, receptors, and proteins are controlled by two key transcription control pathways

• The active nSREBP transcription factor is released from the Golgi in the insig-1(2)/SCAP/SREBP pathway by intramembrane proteolysis, which occurs when the cholesterol levels are low

• It then acts like a gene expression containing sterol regulatory elements (SREs)

• Membrane proteins in the lipid metabolism can have homologous transmembrane sterol sensing domains in them

• Domains like this can help with detection and responses to changes in levels of both lipids and sterols

18.5: The Cell Biology of Atherosclerosis, Heart Attacks, and Strokes

• Atherosclerosis progressively accumulates cholesterol, the extracellular matrix, and inflammatory and other cells

• If the atherosclerotic plaques cause partial or complete blockage of the coronary arteries then the heart cannot get its needed nutrients, which can ultimately cause a heart attack (similarly, this happening to the brain causes a stroke)

• Infection or injury can cause inflammatory responses in the artery wall, which cause foam cells that show atherosclerosis

• Plasma LDL (bad cholesterol) causes the formation of foam cells

• Plasma HDL (good cholesterol) reverses the transport of cholesterol, lessening the risk of atherosclerosis

• Two drugs used to treat atherosclerosis:

  • Statins (reduces cholesterol biosynthesis)

  • Bile acid sequestrants (prevent enterohepatic recycling of bile acids)