Metabolism (Chapter 6) Exam Notes PDF

Metabolism (Chapter 6) 1. Metabolism The sum of all biochemical reactions occurring in the cell that provide energy and create substances that sustain life ○ Catabolism: The breaking down of macromolecules into simpler components, releasing energy in the process...

Metabolism (Chapter 6) 1. Metabolism The sum of all biochemical reactions occurring in the cell that provide energy and create substances that sustain life ○ Catabolism: The breaking down of macromolecules into simpler components, releasing energy in the process. ○ Anabolism: The buildup of macromolecules by combining simpler molecules using the energy released by the catabolic pathway. 2. What is Energy? - Energy is the capacity to do work/ cause change Potential (stored energy) vs. Kinetics (motion) ○ potential energy: chemical, mechanical, gravitational,nuclear ○ kinetic energy: water waves, electricity, muscle contraction, vesicle movement along microtubules 3. Thermodynamics First Law of Thermodynamics ○ Energy cannot be created or destroyed (principle of conservation of energy) but only transformed or transferred from one form to another. Second Law of Thermodynamics ○ None of the energy transfers is completely efficient: some energy is lost as heat or reduced organization → increased entropy (disorder). Gibbs Free Energy (G) is usable energy, or energy available to do work. ○ The change in free energy, ΔG, can be calculated for any chemical reaction from the formula: ΔG = ΔH - TΔS where: T = absolute temperature in K (K = °C + 273) H = change in enthalpy (potential energy) S = change in entropy ○ G < 0: Reaction does NOT require external energy input (spontaneous): Exergonic ○ G > 0: Reaction requires external energy input (not spontaneous): Endergonic  ○ G = 0: The reaction is at equilibrium and cannot do work; organisms reach equilibrium only when they die. 4. Adenosine Triphosphate (ATP) ATP is the energy currency of the cell. ○ Hydrolysis of ATP is a spontaneous reaction and releases a large amount of free energy. ○ It powers cellular reactions with a positive ΔG (coupling). 5. Activation Energy The initial amount of energy required to start a reaction. 6. Enzymes Biological catalysts that lower the activation energy, increasing the rate of the reaction. ○ Enzymes emerge from the reaction unchanged. ○ Enzymes cannot change the Gibbs free energy of the reaction. ○ Enzymes are generally proteins, but RNA has recently been recognized to also have enzymatic activities. Enzymes are highly specific due to the three-dimensional shape of the enzyme's catalytic site. ○ Induced-fit vs. Lock-key fit Enzyme Components ○ Protein (Apoenzyme) ○ Cofactor (inorganic) vs. Coenzymes (organic) Factors That Influence Enzyme Activity ○ Temperature ○ pH Both responsible for denaturation of the proteins. ○ Substrate concentration ○ Inhibitors Competitive vs. Non-competitive Competitive inhibitor: Has a similar structure to the enzyme’s substrate and competes with it for the catalytic or active site. Non-competitive: Binds to the enzyme at a different site called the allosteric site and induces a conformational change that modifies the shape of the catalytic site, consequently inhibiting the substrate’s binding. Feedback Inhibition  The end product of a metabolic pathway becomes the inhibitor of the first enzyme in the pathway, blocking all subsequent steps. Important regulatory mechanism in the cell. Chapter 7: Cellular Respiration GLUCOSE is the major energy source of cells. A. Glucose Oxidation Glucose contains electrons that, when removed (oxidized), become the source of energy to make ATP. The electrons ultimately end up in oxygen to form water. I. Oxidation-Reduction Reactions ○ Also called redox reactions, these partially or completely transfer electrons from donor to acceptor atoms; the donor is oxidized as it releases electrons, and the acceptor is reduced. ○ When completely oxidized, glucose forms CO2; this reaction is spontaneous and releases a lot of energy (~680 kcal/mol). B. Steps in Cellular Respiration Glucose oxidation is performed in a controlled ("step-wise") manner where the electrons are stored in NADH. There are 4 steps in cellular respiration: 1. Glycolysis ○ Occurs in the cytoplasm of both eukaryotic and prokaryotic cells. ○ Each molecule of glucose (6-carbons) is oxidized into 2 molecules of pyruvate (3-carbons) with the production of 4 molecules of ATP (NET ATP: 2 molecules, since 2 ATP were consumed during the energy-investment phase), and reduction of 2 molecules of NAD+ to NADH. 2. Pyruvate Oxidation ○ Occurs in the mitochondrial matrix of eukaryotic cells and in the cytoplasm of prokaryotic cells. ○ Pyruvate (3 carbon) is converted to acetyl-CoA (2 carbon) with the release of 1 molecule of CO2 and reduction of 1 NAD+ to NADH for each molecule of pyruvate. 3. Citric Acid Cycle  ○ Occurs in the mitochondrial matrix of eukaryotic cells and in the cytoplasm of prokaryotic cells. ○ Acetyl-CoA (2 carbon) combines with oxaloacetate (4 carbon) to make citrate (6 carbon). ○ The 2 carbon atoms (from acetyl-CoA) of citrate are further oxidized to produce CO2, NADH, and FADH2. 1 ATP is produced for each Acetyl-CoA entering the cycle. 4. Oxidative Phosphorylation ○ Occurs in the inner mitochondrial membrane of eukaryotic cells and in the plasma membrane of prokaryotic cells. ○ NADH and FADH2, which contain high-energy electrons, are oxidized in the inner mitochondrial membrane (or plasma membrane in prokaryotic cells) to form ATP. ○ A series of proteins (electron transport chain) takes the 2 electrons from NADH and creates a proton gradient across the membrane. ○ The energy of the proton gradient (the proton motive force) is used to make ATP. C. Substrate-Level Phosphorylation Another way to make ATP is through substrate-level phosphorylation, which does not go through the electron transport chain and uses a high-energy phosphate molecule to transfer the phosphate to ADP to form ATP. ATP generated during glycolysis and the citric acid cycle occurs through substrate-level phosphorylation, catalyzed by specific enzymes called kinases. D. In Absence of Oxygen 1. Anaerobic Respiration ○ Some living systems (prokaryotes) use an inorganic molecule as a final electron acceptor. 2. Fermentation ○ Incomplete oxidation of glucose or other carbohydrates in the absence of oxygen. ○ Uses organic compounds (pyruvate) as the terminal electron acceptors and yields a small amount of ATP. Types of Fermentation: Lactic Acid Fermentation Alcoholic Fermentation Chapter 8: Photosynthesis 1. Overview of Photosynthesis Photosynthesis is a non-spontaneous reaction; it requires the input of energy from sunlight. The goal of photosynthesis is to reduce (add electrons) carbon dioxide to make glucose. 2. Location and Process Photosynthesis takes place in chloroplasts of plants and is divided into two parts: A. Light-Dependent Reactions (Light Cycle) Occur in the thylakoids of the chloroplasts. I. Light Absorption ○ Light is absorbed by pigments (e.g., chlorophylls), resulting in charge separation that produces high-energy electrons. II. Electron Transfer ○ The high-energy electrons escape from the pigment molecule and move through the electron-transfer protein system in the thylakoid membrane, generating a proton gradient (proton motive force) and ending up in NADP+ to form NADPH. III. ATP Synthesis ○ The proton motive force provides energy to synthesize ATP via ATP synthase. IV. Water Oxidation ○ Water is oxidized (split) to make oxygen to replenish the lost electrons from the charge separation reaction. V. Key Molecules Produced ○ Three key molecules are made: ATP, NADPH, and O2. B. Light-Independent Reactions (Calvin Cycle, Dark Cycle) Occur in the stroma of the chloroplasts. I. Carbon Dioxide Capture ○ Capture of carbon dioxide (1 carbon) through the stomata by ribulose 1,5-bisphosphate (5 carbon) via the RUBISCO enzyme. II. Synthesis of Glyceraldehyde-3-Phosphate ○ Synthesis of two molecules of glyceraldehyde-3-phosphate (C3; a key glycolysis intermediate) using ATP and NADPH (from the light cycle). III. Glucose Synthesis ○ Six turns of the Calvin Cycle are needed to complete the synthesis of 1 molecule of glucose from 6 molecules of CO2. Chapter 10: Cell Division Cell division has three important functions: The development, growth, and repair of tissues in multicellular animals (Mitosis). The formation of gametes (eggs and sperm) for sexual reproduction in multicellular animals (Meiosis – Ch. 11). The reproduction of an entire unicellular organism (e.g., bacteria). 1. Cell Division in Eukaryotes: Mitosis To divide, a cell must complete several important tasks (it must grow, copy its genetic material, and physically split into two daughter cells) in an organized, predictable series of steps that make up the cell cycle. a) Organization of DNA in Eukaryotic Cells The DNA forms a complex with various protein partners that help package it into a tiny space. This DNA-protein complex is called chromatin. The fundamental unit of chromatin is the nucleosome, made of double-stranded DNA wrapped around a core of eight histone proteins (two each of different histone types - H2A, H2B, H3, and H4). b) The Cell Cycle I. Interphase G1 phase (growth phase), S phase (DNA replication and duplication), G2 phase (preparation for cell division). II. Mitotic Phase Prophase, Prometaphase, Metaphase, Anaphase, Telophase, and Cytokinesis. ○ Be familiar with the key events in each phase.  ○ Recognize the differences between animal and plant cell cytokinesis. 2. Regulation of the Cell Cycle The cell cycle must be regulated because loss of control can result in cancer. a) External Controls Based primarily on surface receptors that recognize and bind signals such as peptide hormones and growth factors, surface groups on other cells, or molecules of the extracellular matrix. The binding triggers internal reactions that speed, slow, or stop cell division. b) Internal Controls The internal controls that monitor progression through the cell cycle include three cell cycle checkpoints to ensure that critical phases do not commence before previous phases are completed correctly. I. G1 Checkpoint Determines whether all conditions are favorable for cell division to proceed. II. G2 Checkpoint Ensures that all chromosomes have been replicated and that the replicated DNA is not damaged. III. M Checkpoint (at the end of metaphase) Ensures that the chromosomes align correctly in the metaphase plate. c) Internal Control System The internal control system that directly regulates cell division involves positive and negative regulators. I. Positive Regulators Promote the progress of the cell cycle and include cyclins and cyclin-dependent kinases (CDKs). ○ CDKs are activated when combined with cyclins and phosphorylate target proteins, regulating their activities. ○ There are four classes of cyclins distinguished by the stage of the cell cycle at which they activate CDKs. II. Negative Regulators Halt the cell cycle and include pRB, p53, and the related p21. ○ Referred to as Tumor Suppressors, since their lack of function results in uncontrolled and continuous growth of the cell (cancer). ○ When DNA damage is detected, p53 arrests the cell cycle in G1 phase until the damage is repaired. If the damage cannot be repaired, it induces apoptosis (programmed cell death), an active process involving the activation of proteases called caspases that cleave specific proteins in the cytoplasm and nucleus, inducing cell death. p53 appears mutated in more than half of human tumors. d) Conversion of Normal Cells to Cancer Cells Besides the alteration of tumor suppressor genes, the conversion of normal cells to cancer cells is also due to mutations occurring in proto-oncogenes, genes that encode proteins that drive the cell cycle forward. Mutated proto-oncogenes are referred to as oncogenes. 3. Cell Division in Prokaryotes: Binary Fission Similar in concept to mitosis but with a different purpose: cell division by mitosis in multicellular organisms causes the organism to grow or to replace old cells, whereas cell division by binary fission is how bacteria reproduce and increase their population. The bacterial chromosome is a closed, circular molecule of DNA, packed into the nucleoid region of the cell. Many bacteria also contain plasmids (small circular double-stranded DNA), which replicate independently of the host chromosome. Replication begins at the origin of replication of the bacterial chromosome, catalyzed by enzymes located in the middle of the cell. Once the origin of replication is duplicated, the two origins migrate to the two ends of the cells. Division of the cytoplasm occurs through a partition of cell wall material that grows. Chapter 11: Meiosis and Sexual Reproduction 1. Sexual Reproduction Occurs only in eukaryotes.  Requires fertilization, the fusion of two haploid cells (gametes) to form a single, unique diploid cell (zygote). ○ The zygote will then develop into an adult organism through tens of rounds of mitosis. Ploidy: the number of sets of chromosomes in a cell. ○ Haploid (n): one copy of each chromosome. ○ Diploid (2n): two copies of each chromosome. 2. Generation of Haploid Cells (Gametes) Meiosis: division of germ cells. Two rounds of nuclear division (meiosis I and II) that halves the chromosome number prior to fertilization, which will restore diploidy. As seen in mitosis, during the premeiotic interphase, DNA replicates, producing two copies, sister chromatids, of each chromosome. Meiotic phases are named like the mitotic ones: prophase, prometaphase, metaphase, anaphase, telophase, and cytokinesis. Meiosis I: First Cell Division Main Events NOT Occurring in Mitosis: ○ Prophase I: Each chromosome pairs with its homolog. The two homologs (bivalent) are held together by the synaptonemal complex. While paired, non-sister chromatids exchange DNA segments by crossing-over (chiasmata are the sites of crossing-over). ○ Metaphase I: The tetrads (4 sister chromatids) align at the metaphase plate, and each homologous chromosome is oriented toward the opposite pole of the cell. ○ Anaphase I: The homologous chromosomes of each pair segregate and move to opposite spindle poles, reducing the chromosome number to the haploid value. ○ Telophase and Cytokinesis I: Two haploid daughter cells are formed, but each chromosome still contains two chromatids. Meiosis II: Second Cell Division Produces four genetically different haploid cells. The events are similar to those occurring during mitotic division, except for the final result: four haploid cells, each containing half the number of chromosomes, are generated. 3. Genetic Variability in Offspring Why don’t you look exactly like your parents or your siblings, except in the case of identical twins? Sexual reproduction introduces genetic variability by three mechanisms: ○ Crossing Over: Between homologous chromosomes and genetic recombination (Prophase I). ○ Independent Assortment: Of homologous chromosomes (Metaphase I). The random alignment of homologous chromosomes at the metaphase plate ensures the random distribution of chromosomes in the daughter cells. ○ Random Joining: Of female and male gametes during fertilization. Genetic Diversity is key in the rate of evolution by natural selection. 4. Mitosis vs. Meiosis Mitosis Meiosis Requires one nuclear division Requires two nuclear divisions Chromosomes do not synapse nor cross Chromosomes synapse and cross over over Centromeres dissolve in mitotic anaphase Centromeres survive in anaphase I Preserves chromosome number Halves chromosome number Produces 2 daughter nuclei Produces 4 daughter nuclei Produces daughter cells genetically Produces daughter cells genetically identical to parents and to each other different from parents and each other Used for asexual reproduction and growth Used only for sexual reproduction