Week 2 Lecture 3 v2 PDF

Week 2 Lecture 3 Learning Objectives By the end of this chapter you should be able to: Identify cell compartments, membranes and structure. Identify the functions of cell organelles. Explain protein synthesis and the role of ribosomes. Describe energy release and consumption in chemic...

Week 2 Lecture 3 Learning Objectives By the end of this chapter you should be able to: Identify cell compartments, membranes and structure. Identify the functions of cell organelles. Explain protein synthesis and the role of ribosomes. Describe energy release and consumption in chemical reactions. Discuss the role of glycolysis Role of glucose transporters in regulating glucose metabolism  Components of Cells Copyright © 2018 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part, except for use as permitted in a license distributed with a certain product or service or otherwise on a password-protected website for classroom use. Cytoplasmic Matrix Cytoskeleton provides Cytoskeleton the following: Components: Structural support Microtubules Framework for Intermediate organelles filaments Pathway for Microfilaments intercellular communication  Mitochondrion Mitochondrial membrane: Outer membrane — relatively porous Inner membrane Selectively permeable Site of electron transport chain View inside a macrophage highlighting the nucleus and mitochondria. This is a confocal microscope image showing the cell nucleus (blue) with areas of high DNA concentration (light blue) and the tubular mitochondria organized into fused networks (green).  HeLa Cells (A) Deconvoluted STED images showing changes in the mitochondrial morphology under concomitant change of the cristae density upon nutrition starvation for 3 and 12 h (HBSS containing Ca2+ and Mg2+). Morphological changes of the mitochondrial inner membrane captured by STED microscopy Nucleus Largest organelle: Surrounded by nuclear envelope Contains DNA: Cell genome is the entire set of genetic information. Nucleolus: Site of RNA transcription Ribosome assembly/synthesis-The process begins in the nucleus and completed in the cytoplasm. Nucleic Acids DNA and RNA Adenine, guanine, and cytosine in both: Uracil in RNA only. Thymine in DNA only. Complimentary base pairing of double stranded DNA RNA is single stranded—But can fold on itself to generate complex secondary structures. Hyperuricemia: Accumulation of high concentrations of uric acid causes uric acid to clump together in sharp crystals. These crystals can settle in your joints and cause gout, a painful form of arthritis. They can also build up in your kidneys and form kidney stones. RNA Comes in Diverse Shapes and plays roles beyond translation (A) C. elegans is a useful model organism for understanding how different cell types develop. (B) Ambros and Ruvkun studied the lin-4 and lin-14 mutants. Ambros had shown that lin-4 appeared to be a negative regulator of lin- 14. (C) Ambros discovered that the lin- 4 gene encoded a tiny RNA, microRNA, that did not code for a protein. Ruvkun cloned the lin-14 gene, and the two scientists realized that the lin-4 microRNA sequence matched a complementary sequence in the lin-14 mRNA. (A) C. elegans is a useful model organism for understanding how different cell types develop. (B) Ambros and Ruvkun studied the lin-4 and lin-14 mutants. Ambros had shown that lin-4 appeared to be a negative regulator of lin- 14. (C) Ambros discovered that the lin- 4 gene encoded a tiny RNA, microRNA, that did not code for a protein. Ruvkun cloned the lin-14 gene, and the two scientists realized that the lin-4 microRNA sequence matched a complementary sequence in the lin-14 mRNA. Ruvkun cloned let-7, a second gene encoding a microRNA. The gene is conserved in evolution, and it is now known that microRNA regulation is universal among multicellular organisms. Ribosomes link amino acids together to generate proteins  Steps of Protein Synthesis Copyright © 2018 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part, except for use as permitted in a license distributed with a certain product or service or otherwise on a password-protected website for classroom use. Biological Energy ATP: major storage form of energy in cells Paul Boyer (Boyer Hall): Received the Nobel Prize for his work on understanding how ATP-Synthase generates ATP. ATP synthase is a protein that catalyzes the formation of the energy storage molecule ATP using ADP and inorganic phosphate (Pi). ATP synthase is a molecular machine that rotates as protons pass through, joining ADP and Pi. Energy is needed for the following: Physical exertion Anabolism Active transport Transfer of genetic information Energy Release and Consumption in Chemical Reactions Energy comes from macronutrients Free energy (G) Transferred from one form to another Units of energy (cal, kcal, J, kJ): 1 cal=4.18 J, or 1 kcal=4.18 kJ Potential energy released from bonds of nutrients Exothermic and Endothermic Reactions (2 of 3) Copyright © 2018 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part, except for use as permitted in a license distributed with a certain product or service or otherwise on a password-protected website for classroom use. Exothermic and Endothermic Reactions (3 of 3) Copyright © 2018 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part, except for use as permitted in a license distributed with a certain product or service or otherwise on a password-protected website for classroom use. The Role of High-Energy Phosphate in Energy Storage 95% of the human body's total creatine and phosphocreatine stores are found in skeletal muscle, while the remainder is distributed in the blood, brain, testes, and other tissues. Copyright © 2018 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part, except for use as permitted in a license distributed with a certain product or service or otherwise on a password-protected website for classroom use. The Role of High-Energy Phosphate in Energy Storage Copyright © 2018 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part, except for use as permitted in a license distributed with a certain product or service or otherwise on a password-protected website for classroom use.  Glycolysis Glykis: Sweet Lysis: Splitting Glycolysis: Splits one molecule of glucose (6 carbon molecule) into two molecules of pyruvate (3 carbon molecule). Free energy generated during this process produces two molecules of ATP and and 2 molecules of NADH. NADH production consumes NAD+. ADP is utilized to add a high energy phosphate to make ATP. Fate of Glucose  Glucose Metabolism Complete Glucose Oxidation Glucose + 6O2 = 6 CO2 + H2O dG=-2840 kJ/mol Glycolysis Glucose + 2NAD+ = 2Pyruvate + 2NADH + 2H+ dG=-146 kJ/mol 5.2% of total free energy that can be released by glucose is released during glycolysis.  Glycolysis Glycolysis takes place in the cytosol where enzymes involved in glucose processing are found. Glycolysis is the major ATP generating pathway found in cells like cornea, lens, erythrocytes, etc. These are cells that have little access to oxygen and thus largely reliant on non-oxidative processes.  Glycolysis Essential for tissues that are highly reliant on glucose, like the brain. Under anaerobic conditions, glycolysis generates lactate and ATP.  Stage of 1 of Glycolysis: Energy Requiring Step Stage 1 (Reactions 1-5): A preparatory stage in which glucose is phosphorylated, converted to fructose which is again phosphorylated and cleaved into two molecules of glyceraldehyde-3-phosphate. In this phase there is an investment of 2 molecules.  Stage of 1 of Glycolysis: Energy Requiring Step 1. Once phosphorylated gets trapped in cell (no longer able to be transported by GLLUTs). 2. This change from phosphoglucose to phosphofructose allows the eventual split of the sugar into two three-carbon molecules. 3. It is active when the concentration of ADP is high; it is less active when ADP levels are low and the concentration of ATP is high.  Stage of 2 of Glycolysis: Energy Generating Step Stage 2 (Reactions 6-10): The 2 molecules of glyceraldehyde-3-phosphate are converted to pyruvate with concomitant generation of four ATP molecules and two molecules of NADH. Thus there is a net gain of two ATP molecules per molecule of glucose during glycolysis.  Stage of 2 of Glycolysis: Energy Generating Step Step 6: The sixth step in glycolysis (Figure 3) oxidizes the sugar (glyceraldehyde-3- phosphate), extracting high-energy electrons, which are picked up by the electron carrier NAD+, producing NADH. The continuation of the reaction depends upon the availability of the oxidized form of the electron carrier, NAD+. NAD+ can be generated by pyruvate to lactate conversion. If NAD+is not available, the second half of glycolysis slows down or stops. If oxygen is available in the system, the NADH will be oxidized readily, though indirectly, and the high-energy electrons from the hydrogen released in this process will be used to produce ATP. In an environment without oxygen, an alternate pathway (fermentation) can provide the oxidation of NADH to NAD+. Anaerobic and Aerobic Glycolysis Aerobic Glycolysis Aerobic glycolysis is the glycolytic pathway which occurs in the cytosol in the presence of oxygen. When compared to anaerobic glycolysis, this pathway is much more efficient and produces more ATP per glucose molecule. In aerobic glycolysis, the end product, pyruvate is transferred to mitochondria for the initiation of Citric acid cycle. Therefore, the ultimate products of aerobic glycolysis are 34 ATP molecules, water, and carbon dioxide. Anaerobic Glycolysis Anaerobic glycolysis takes place in the cytoplasm when a cell lacks oxygenated environment or lacks mitochondria. In this case, NADH is oxidized to NAD+ in the cytosol by converting pyruvate into lactate. Anaerobic glycolysis produces (2 lactate + 2 ATP + 2 H2O + 2 H+) from one glucose molecule. Unlike the aerobic glycolysis, anaerobic glycolysis produces lactate, which reduces the pH and inactivates the enzymes.  Anaerobic and Aerobic Glycolysis What is the difference between Aerobic and Anaerobic Glycolysis? Aerobic glycolysis occurs in oxygen rich environments, whereas anaerobic glycolysis occurs in oxygen lack environments. Aerobic glycolysis is more efficient than anaerobic glycolysis; hence it produces a large amount of ATP than anaerobic glycolysis. Aerobic glycolysis occurs only in eukaryotes while anaerobic glycolysis occurs in both prokaryotes and eukaryotes. Unlike in anaerobic glycolysis, the end product of Aerobic glycolysis (pyruvate) is used to initiate other pathways in mitochondria. Anaerobic glycolysis produces 2ATPs per glucose molecule while aerobic glycolysis produces 36 to 38 ATPs per glucose molecule. Ultimate end product of anaerobic glycolysis is lactate, which may be harmful to the cell itself, whereas that of aerobic glycolysis is water and carbon dioxide, which are not harmful to cells. Unlike in anaerobic glycolysis, NADH + H+ undergo oxidative phosphorylation in the presence of oxygen in aerobic glycolysis. Pyruvate is reduced to lactate during anaerobic glycolysis whereas, during aerobic glycolysis, pyruvate is oxidation to acetyl coenzyme A (acetyl- CoA). Membrane Transporters of Glucose Membrane Transporters of Glucose Membrane Transporters of Glucose Membrane Transporters of Glucose  Membrane Transporters of Glucose GLUT1 was the first GLUT identified and is the most ubiquitously expressed glucose transporter. It allows glucose to cross the blood–brain barrier and supplies glucose to the developing central nervous system during embryogenesis. GLUT1 is responsible for the supply of glucose to erythrocytes, endothelial cells of the brain, and most fetal tissue. Its importance is evident in GLUT1 deficiency syndrome in which patients experience seizures beginning in early infancy due to insufficient glucose supply to the brain. Treatment includes strict adherence to a ketogenic diet that raises levels of ketone bodies in the blood to be used as fuel for the brain and other tissues.  Membrane Transporters of Glucose GLUT2 is a low-affinity, high-capacity transporter with predominant expression in the β-cells of the pancreas, liver, small intestine, and kidney. GLUT2 is involved in the transport of most monosaccharides from enterocytes into the portal blood via the basolateral membrane. And when the concentration of glucose in the intestinal lumen is high, it can transport glucose and fructose into the enterocyte through the brush border. The rate of transport is highly dependent upon the blood glucose concentration. In the pancreas, GLUT2 appears to be the sensitive indicator of blood glucose levels and is involved in the release of insulin from the β-cells.  Membrane Transporters of Glucose GLUT3 is a high-affinity glucose transporter with predominant expression in tissues such as the brain and neurons that are highly dependent on glucose as a fuel. It is also expressed in cells and tissues that have a high requirement for glucose such as spermatozoa, the placenta, and preimplantation embryos. Some data suggest that a possible dysregulation of GLUT3 might lead to glucose deficits in the brain and thus to dyslexia in children.  Membrane Transporters of Glucose GLUT4 is the primary means by which insulin regulates the cellular uptake of blood glucose in muscle and adipose tissue. Other cells and tissues such as the liver, kidneys, erythrocytes, and brain do not express GLUT4 and therefore are not dependent upon insulin for glucose uptake. One of the actions of insulin is to cause the translocation of GLUT4 from intracellular storage vesicles to the plasma membrane (discussed in the next section).  Membrane Transporters of Glucose GLUT5 is highly specific for fructose and does not recognize glucose. It is expressed primarily in the small intestine and to a lesser degree in kidney, brain, skeletal muscle, and adipose tissue. Its main function is to transport dietary fructose across the brush border membrane of enterocytes. Electron Microscopy of Insulin Secreting Cells  Glycemic Index Calculating Glycemic Index The elevation in blood glucose level above the baseline following consumption of a high-glycemic index food or 50 g of glucose in a reference food (glucose or white bread). The glycemic index of the reference food is by definition equal to 100. The elevation of blood glucose levels above the baseline following the intake of 50 g of glucose in a low-glycemic index food. The glycemic index is calculated by dividing the area under the curve for the test food by the area under the curve for the reference food and multiplying the result by 100. Some studies of GI have used glucose as the reference food, while others used white bread (Table 3.3). The reference food is assigned a score of 100. In practice, the GI is measured by determining the elevation of blood glucose for 2 hours following ingestion and plotting the values against time. The area-under- the-curve for the test food is divided by the area-under-the-curve for the reference food, then multiplied by 100. If glucose is used as the reference food and assigned a GI of 100, white bread has a GI of about 71. When white bread is used as the reference, some foods will have a GI of greater than 100. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982099/#:~:text=The%20glycemic%20index%20(GI)%20ranks, same%20test%20portions%20(15).