Membrane Structure and Transport - Kevin Ahern's BB 451 Lecture #32 2017

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Highlights of Lipids/Membranes 1. Eicosanoids are compounds made from the 20 carbon fatty acid, arachidonic acid. These include prostanoids, thromboxanes, leukotrienes and endocannabinoids. 2. Prostaglandins are like hormones, but act very close to the point of synthesis. They stimulate swelling/inflammation, creating pain, uterine contractions, and the synthesis of intestinal tissue. 3. Prostaglandins are made from arachidonic acid by cyclooxygenases. Cyclooxygenases catalyze formation of a bond that creates a cyclic structure in arachidonic acid and adds one or more oxygens to it. 4. There are different COX enzymes, called COX 1, COX 2, and COX 3. 5. COX 1 enzymes are inhibited by aspirin and other related compounds. These compounds are called Non-Steroidal Anti-Inflammatory Drugs (NSAIDS). 6. Drug manufacturers sought inhibitors of COX 2 enzymes to see if they could make a pain-kiliing NSAID that didn't affect stomach tissue. Several, such as VIOXX and Celebrex were made, but some of them had negative effects on heart tissue and had to be withdrawn. 7. The cannabinoid known as anandamide is made from arachidonic acid and ethanolamine. It is called an endocannabinoid in animals and acts on specific brain receptors. Phytocannabinoids are compounds made in plants, such as marijuana, that affect the same receptors. 8. Endocannabinoids are responsible for pain reduction and experiences like runners' high. They are synthesized during periods of heavy exercise. I didn't mention it in class, but the receptor bound by endocannabinoids is the same one affected by chocolate. 9. Steroids are lipids that are derived from cholesterol. Cholesterol is found in the membrane of cells and is important for membrane stability. Cholesterol is prominent in brain membranes - up to 14% of the dry weight of brain. Compounds related to cholesterol made in plants are called phytosterols. 10. Cholesterol is a precursor of two important classes of compounds - steroid hormones and bile acids. Steroid hormones include mineralocorticoids, progestagens, glucocorticoids, and the sex hormones - androgens and estrogens. 11. Fat soluble vitamins include vitamins A,D, E, and K. Vitamin A comes in several forms.(Note - this is a correction from the video lecture). They include the alcohol form, known as retinol. This is primarily the storage form. An aldehyde form is known as retinal and is the form found in vision (wrongly stated in class as retinol). Retinal comes in two forms - the all trans form and a form with a single cis bond known as 11-cis retinal. All vision arises from isomerization of the 11-cis form in the eye to the all trans form. 12. Vitamin D is made from cholesterol. It is important for calcium and phosphate absorption/metabolism and the level of its active form is carefully controlled by the body. Synthesis of vitamin D in the body requires UV light. 13. Vitamin E is an antioxidant in the membrane bilayer and may protect against reactive oxygen species. 14. Vitmain K is involved in blood clotting. 15. A lipid bilayer has a polar exterior facing water and a non-polar interior. As such, the bilayer provides a barrier to polar and non-polar substances. Glycerophospholipids and sphingolipids in an aqueous environment will spontaneously form a lipid bilayer. 16. Lipids in lipid bilayers are not evenly distributed. 17. There are two types of movement of lipids in membranes - lateral or transverse. 18. Lateral movements occur freely and rapidly in fluid membranes. 19. Transverse movements require enzymes for movement from one side to the other. These include flippases, floppases, and scramblases. 20. Membrane fluidity is determined by the composition of fatty acids in the bilayer's glycerophospholipids and sphingolipids. Shorter, more unsaturated fatty acids favor more fluidity at lower temperatures. 21. Membranes transition from more solid-like to more liquid-like over a range of temperature. The mid-point of this temperature ranges is known as the Tm. 22. Cholesterol in a membrane has the effect of widening the range of transition, but does not change the Tm. Membrane Transport 1. Lipid bilayers create virtually impermeable barriers to movement of most molecules except water, carbon dioxide, carbon monoxide, and oxygen. 2. Most biochemicals do not readily cross lipid bilayers. Differences in concentration of these materials across a membrane, create electrical or chemical gradients. These are sources of potential energy. 3. Osmotic pressure is a good example of a potential energy created by a chemical gradient against a semi-permeable membrane. 4. Four types of membrane proteins are integral (protein projects through both sides of the membrane), peripheral (protein projects into only one side of the membrane), anchored (protein is linked to a molecule embedded in the lipid bilayer, or associated (protein associating with a membrane by interacting with a membrane protein).