BCH3033 Biochemistry 1 Chapter 10 b PDF

BCH3033: Biochemistry 1 Chapter 10 b 03.15.2023 Donella Beckwith, Ph.D. [email protected] 1 Some Common Types of Storage and Membrane Lipids 2 Membrane lipids are composed of hydrophobic tails attached to polar head groups. Cellular membranes are composed of a variety of lipids, including glyceropho...

BCH3033: Biochemistry 1 Chapter 10 b 03.15.2023 Donella Beckwith, Ph.D. [email protected] 1 Some Common Types of Storage and Membrane Lipids 2 Membrane lipids are composed of hydrophobic tails attached to polar head groups. Cellular membranes are composed of a variety of lipids, including glycerophospholipids and sterols. These lipids are used for structuring membranes as well as for displaying molecules on the membrane surfaces for signaling and molecular recognition. 3 Sterols Have Four Fused Carbon Rings sterols = structural lipids present in the membranes of most eukaryotic cells Have a characteristic structure: – steroid nucleus: consists of four fused rings almost planar relatively rigid 4 Cholesterol cholesterol = major sterol in animal tissues – amphipathic – polar head group – nonpolar hydrocarbon body – membrane constituents – similar to stigmasterol in plants and ergosterol in fungi 5 Sterols Serve as Precursors for Products with Specific Biological Activities For example: steroid hormones are biological signals that regulate gene expression bile acids are polar derivatives of cholesterol (amphipathic) – they emulsify dietary fats in the intestine to make them more readily accessible to digestive lipases 6 Question 1 Which statement regarding cholesterol is false? A. B. C. D. It is the precursor for steroid hormones. It is the precursor for bile acids. It is not usually a component of eukaryotic membranes. It has a hydrophilic functional group. 7 Question 2 Membrane lipids do NOT include: A. B. C. D. glycerophospholipids. triacylglycerols. sphingolipids. glycolipids. 8 Lipids have uses in the cell beyond energy storage and membranes construction. Many lipids are present in the cell at smaller amounts than those making up membranes or being stored as fat. These lipids can function as cellular messengers, hormones, electron carriers, or pigments. – Some play active roles in metabolic traffic 9 Phosphatidylinositols and Sphingosine Derivatives Act as Intracellular Signals phosphatidylinositol (PI) and its phosphorylated derivatives regulate cell structure and metabolism x 6 1 5 2 4 3 10 Phosphatidylinositol 4,5Bisphosphate (PIP2) in the cytoplasmic face of plasma membranes serves as a reservoir of messenger molecules that are released in response to extracellular signals – phospholipase C hydrolyzes PIP2 to IP3 and diacylglycerol (DAG) (intracellular messengers of the calcium pathway) 5 4 11 Inositol Phospholipids Serve As Points of Nucleation For supramolecular complexes involved in signaling proteins or in exocytosis More specifically they bind to phosphatidylinositol 3,4,5trisphosphate (PIP3) in the plasma membrane – initiates formation of multienzyme complexes at the membrane’s cytosolic surface (For those interested this topic continues in chapter 12) 12 Membrane Sphingolipids Serve As Sources of Intracellular Messengers ceramide and sphingomyelin are potent regulators of protein kinases ceramide or its derivatives are involved in the regulation of: – cell division – differentiation – migration – programmed cell death (For those interested this topic continues in chapter 12) 13 Question 3 Which statement is false? A. Phosphorylated derivatives of phosphatidylinositol regulate cell structure and metabolism. B. Extracellular signals activate a specific phospholipase C in the membrane, which hydrolyzes PIP2 to release two products that act as intracellular messengers. C. Formation of PIP3 in response to extracellular signals brings the proteins together in signaling complexes at the surface of the plasma membrane. D. PIP3 is a potent regulator of protein kinases. 14 Eicosanoids Carry Messages to Nearby Cells eicosanoids = paracrine hormones, substances that act only on cells near the point of hormone synthesis instead of being transported in the blood involved in: – reproductive function – inflammation, fever, and pain associated with injury or disease – formation of blood clots – regulation of blood pressure 15 – gastric acid secretion Eicosanoids Are Derived From Arachidonic Acid Eicosanoids are derived from arachidonic acid (20-C PUFA) Four major classes of eicosanoids = prostaglandins, thromboxanes, leukotrienes, and lipoxins 16 Question 4 Which statement regarding eicosanoids is false? A. They are produced from arachidonate. B. They are classified as neither prostaglandins nor thromboxanes. C. They act as paracrine hormones. D. They have many different effects. 17 Prostaglandins (PG) prostaglandins (PG) = class of eicosanoids that contain a fivecarbon ring array of functions: – stimulate contraction of the smooth muscle of the uterus – affect blood flow to specific organs, the wake-sleep cycle, and the responsiveness of certain tissues to hormones – elevate body temperature and cause inflammation and pain 18 Thromboxanes (TX) thromboxanes (TX) = class of eicosanoids that have a sixmembered ring containing an ether produced by platelets (also called thrombocytes) act in the formation of blood clots and reduction of blood flow to the site of a clot 19 Leukotrienes (LT) leukotrienes (LT) = class of eicosanoids that contain three conjugated double bonds powerful biological signals – leukotriene D4 induces contraction of the smooth muscle lining the airways to the lung 20 Lipoxins (LX) lipoxins (LX) = last class of eicosanoids that are linear and contain several hydroxyl groups along the chain potent anti-inflammatory agents 21 Matúš Soták, Et al., Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures, iScience, 25(7) 2022, 104602, ISSN 2589-0042, https://doi.org/10.1016/j.isci.2022.104602. Question 5 A novel subclass of thromboxane was discovered in lipids isolated from a newly discovered poison dart from the Amazon valley. What unique structural feature is likely present in these lipids? A. B. C. D. four conjugated double bonds a six-membered ring a long-chain alcohol bound to a double ring a five-membered ring 22 Steroid Hormones Carry Messages between Tissues steroids = oxidized derivates of sterols – lack the alkyl chain attached to ring D of cholesterol – more polar than cholesterol steroid hormones move through the bloodstream (on protein carriers) to target tissues binding to highly specific receptor proteins in the nucleus triggers changes in gene expression 23 Steroids Derived From Cholesterol 24 Question 6 Steroid hormones: A. act locally. B. travel through the bloodstream on lipid carriers. C. bind to receptor proteins in the nucleus to change metabolism. D. have low affinity for their receptors. 25 Vitamins D and A Are Hormone Precursors vitamins = compounds that are essential to the health of humans and other vertebrates but cannot be synthesized – Must be obtained from your diet fat-soluble vitamins include the groups A, D, E, and K – Soluble in nonpolar organic solvents 26 Vitamin D3 and Calcitriol vitamin D3 (cholecalciferol) = formed in the skin from 7dehydrocholesterol in a photochemical reaction driven by the UV component of sunlight – not biologically active – converted by enzymes in the liver and kidney to calcitriol 27 Vitamin D Deficiencies deficiency leads to defective bone formation and the disease rickets 28 Vitamin D3 Production and Metabolism calcitriol = hormone that regulates calcium uptake in the intestine and calcium levels in the kidney and bone 29 Question 7 Which statement is false regarding vitamin D3? A. Vitamin D3 serves as a hormone precursor. B. Vitamin D3 forms from a photochemical reaction driven by UV light. C. Vitamin D3 is biologically active in the intestine, kidney, and bone. D. Vitamin D3 is a cure for the disease rickets. 30 Vitamin A1 and All-Trans-Retinoic Acid vitamin A1 (all-transretinol) = acts in processes of development, cell growth and differentiation, and vision – can be stored for some time in the body vitamin A1 or β-carotene can be converted enzymatically to all-transretinoic acid all-trans-retinoic acid = retinoid hormone that acts through a family of nuclear receptor proteins to regulate gene expression 31 Carotenoids carotenoids = natural products with a characteristic extensive system of conjugated double bonds, which makes possible their strong absorption of visible light (450–470 nm) – β-carotene pigment is a source of vitamin A 32 Vitamin A Deficiencies in pregnant women, leads to congenital malformations and growth retardation in the infant in adults, leads to dryness of skin, eyes, and mucous membranes, and night blindness “golden rice” = genetically engineered rice enriched in β-carotene 33 Question 8 Vitamin A1 and its derivatives: A. B. C. D. are involved in regulating cell growth and differentiation. contain only trans C–C double bonds. are not stored in the body in significant amounts. act as antioxidants. 34 Vitamins E and K and the Lipid Quinones Are Oxidation-Reduction Cofactors vitamin E = collective name for a group of lipids called tocopherols tocopherols = hydrophobic compounds that contain a substituted aromatic ring and a long isoprenoid side chain – associate with cell membranes, lipid deposits, and lipoproteins – biological antioxidants 35 Vitamin E Deficiencies cause scaly skin, muscular weakness and wasting, and sterility very rare in humans principal symptom is fragile erythrocytes 36 Question 9 Which statement is true? A. B. C. D. Vitamin E is a hormone precursor. Vitamin D regulates milk production in mammary glands. Prostaglandins are found only in the prostate gland. Membrane sphingolipids can be used to produce intracellular messengers. 37 Vitamin K vitamin K = contains an aromatic ring that undergoes a cycle of oxidation and reduction during the formation of active prothrombin, a blood plasma protein essential in blood clotting 38 Vitamin K Deficiencies slow blood clotting extremely uncommon in humans 39 Question 10 Which of the following hormones regulate calcium uptake in the intestines and calcium levels in the kidney and bone? A. B. C. D. tocopherols carotenoids calcitriol 7-dehydrocholesterol 40 Warfarin warfarin = a synthetic compound that inhibits the formation of active prothrombin – potent rodenticide – invaluable anticoagulant drug for treating humans at risk for excessive blood clotting 41 Dolichols Activate Sugar Precursors for Biosynthesis dolichols = isopenoid alcohols that activate and anchor sugars to cellular membranes – sugar groups are then used in the synthesis of complex carbohydrates, glycolipids, and glycoproteins – allow attached sugars to participate in sugar-transfer reactions 42 Many Natural Pigments Are Lipidic Conjugated Dienes conjugated dienes = have carbon chains with alternating single and double bonds – allow the delocalization of electrons – compounds can be excited by visible light 43 Question 11 Which statement is false? A. Ubiquinone is involved in electron transport. B. Natural pigments are often lipids with conjugated double bonds. C. Many lipids have structures based on repeating isoprene units. D. Vitamin K is essential for the dissolution of blood clots. 44 Lipid Extraction Requires Organic Solvents neutral lipids are extracted with ethyl ether, chloroform, or benzene – does not permit lipid clustering driven by the hydrophobic effect membrane lipids are extracted by ethanol or methanol – reduces the hydrophobic interactions among lipid molecules – weakens the hydrogen bonds and electrostatic interactions that bind membrane lipids to membrane proteins 45 Adsorption Chromatography Separates Lipids of Different Polarity lipids in mixtures can be separated based on their polarity and interactions with polar materials such as silica, using adsorption chromatography methods such as HPLC or TLC 46 Gas Chromatography Resolves Mixtures of Volatile Lipid Derivatives GC volatilizes lipids so that they can be carried by a stream of inert gas and resolved based on their ability to partition into a soluble column material 47 Question 12 Which method is NOT typically used in the purification of lipids? A. B. C. D. ammonium sulfate precipitation extraction with organic solvents thin-layer chromatography gas chromatography 48 Question 13 Lipids were extracted from plasma membranes. What method could be used to separate them by exploiting differences in volatility? A. B. C. D. gas chromatography adsorption-column chromatography thin-layer chromatography mass spectroscopy 49 Mass Spectrometry Reveals Complete Lipid Structure allows the analysis of crude mixtures of lipids without prefractionation can determine the length of a hydrocarbon chain or positions of double bonds 50 Question 14 Mass spectrometry: A. B. C. D. cannot be used with lipids other than fatty acids. can determine the mass but not the identify of a lipid. can be used to identify individual lipids in complex mixtures. cannot determine the locations of double bonds in a fatty acid. 51