Bioenergetics - CIS class-LS101 Introduction to Biology

Bioenergetics CIS class-LS101 Introduction to Biology Dr. Mrigya Babuta Assistant Professor Department of Animal Biology, School of Life Sciences  Catabolic pathways deliver chemical energy in the form of ATP, NADH, NADPH, and FADH2. These energy...

Bioenergetics CIS class-LS101 Introduction to Biology Dr. Mrigya Babuta Assistant Professor Department of Animal Biology, School of Life Sciences  Catabolic pathways deliver chemical energy in the form of ATP, NADH, NADPH, and FADH2. These energy carriers are used in anabolic pathways to convert small precursor molecules into cellular macromolecules.  Three possible catabolic fates of the pyruvate formed in glycolysis What is Glycolysis? Glycolysis Glycolysis Glycolysis  Energy consumption Preparatory Phase Payoff Phase Each molecule of glucose that passes through the preparatory phase (a), two molecules of glyceraldehyde 3-phosphate are formed ; both pass through the payoff phase (b). For each glucose molecule, two ATP Four ATP are produced in the payoff phase is utilized Net yield of two ATP per molecule of glucose converted to pyruvate.  Summary Glycolysis is a near-universal pathway by which a glucose molecule is oxidized to two molecules of pyruvate, with energy conserved as ATP and NADH. All 10 glycolytic enzymes are in the cytosol, and all 10 intermediates are phosphorylated compounds of three or six carbons. In the preparatory phase of glycolysis, ATP is invested to convert glucose to fructose 1,6-bisphosphate. The bond between C-3 and C-4 is then broken to yield two molecules of triose phosphate. In the payoff phase, each of the two molecules of glyceraldehyde 3- phosphate derived from glucose undergoes oxidation at C-1; the energy of this oxidation reaction is conserved in the form of one NADH and two ATP per triose phosphate oxidized. The net equation for the overall process is Summary  Three possible catabolic fates of the pyruvate formed in glycolysis  Pyruvate to Lactate lactate dehydrogenase Condition in which this reaction is Favored? Cell types such as erythrocytes, which have no mitochondria and thus cannot oxidize pyruvate to CO2 Pyruvate to Alcohol  Gluconeogenesis The important precursors of glucose in animals are three carbon compounds such as lactate, pyruvate, and glycerol, as well as certain amino acids Formation of one molecule of glucose from pyruvate requires 4 ATP, 2 GTP, and 2 NADH; it is expensive In mammals, gluconeogenesis in the liver, kidney, and small intestine provides glucose for use by the brain, muscles, and erythrocytes. Animals cannot convert acetyl-CoA derived from fatty acids into glucose; plants and microorganisms can. Gluconeogenesis- Glucose synthesis Glyconeogenesis- Glycogen synthesis  Fate of Pyruvate The conversion of pyruvate to acetyl groups, then the entry of those groups into the citric acid cycle, also called the tricarboxylic acid (TCA) cycle or the Krebs cycle (after its discoverer, Hans Krebs).  Pyruvate Is Oxidized to Acetyl-CoA and CO2 The overall reaction catalyzed by the pyruvate dehydrogenase complex is an oxidative decarboxylation, an irreversible oxidation process in which the carboxyl group is removed from pyruvate as a molecule of CO2 and the two remaining carbons become the acetyl group of acetyl-CoA.  Citrate synthase At each turn of the cycle, three NADH, one FADH2, one GTP (or ATP), and two CO2 are released in oxidative decarboxylation reactions.  Flavoproteins contain a very tightly, sometimes covalently, bound flavin nucleotide, either FMN or FAD. The oxidized flavin nucleotide can accept either one electron (yielding the semiquinone form) or two (yielding FADH2 or FMNH2).  Summary In citric acid cycle (Krebs cycle, TCA cycle) compounds derived from the breakdown of carbohydrates, fats, and proteins are oxidized to CO2, with most of the energy of oxidation temporarily held in the electron carriers FADH2 and NADH. During aerobic metabolism, these electrons are transferred to O2 and the energy of electron flow is trapped as ATP. Acetyl-CoA enters the citric acid cycle in the mitochondria of eukaryotes, the cytosol of bacteria. In seven sequential reactions, including two decarboxylations, the citric acid cycle converts citrate to oxaloacetate and releases two CO2. For each acetyl-CoA oxidized by the citric acid cycle, the energy gain consists of three molecules of NADH, one FADH2, and one nucleoside triphosphate (either ATP or GTP).  Summary Besides acetyl-CoA, any compound that gives rise to a four- or five carbon intermediate of the citric acid cycle—for example, the breakdown products of many amino acids— can be oxidized by the cycle. The citric acid cycle is amphibolic, serving in both catabolism and anabolism; cycle intermediates can be drawn off and used as the starting material for a variety of biosynthetic products. Vertebrates cannot synthesize glucose from acetate or from the fatty acids that give rise to acetyl-CoA. In TCA cycle- At each turn of the cycle, three NADH, one FADH2, one GTP (or ATP), and two CO2 are released in oxidative decarboxylation reactions. Energy Produced Till now is: 1. 5NADH 2. 3ATP (or 2ATP and 1 GTP) 3. 1 FADH2  Electron Transport Chain The electron transport chain is a collection of membrane-embedded proteins and organic molecules, most of them organized into four large complexes labeled I to V. In eukaryotes, many copies of these molecules are found in the inner mitochondrial membrane. In prokaryotes, the electron transport chain components are found in the plasma membrane. As the electrons travel through the chain, they go from a higher to a lower energy level, moving from less electron-hungry to more electron-hungry molecules. Energy is released in these “downhill” electron transfers, and several of the protein complexes use the released energy to pump protons from the mitochondrial matrix to the intermembrane space, forming a proton gradient  Role of Electron Transport Chain Delivery of electrons by NADH and FADH\[_2\]. Reduced electron carriers (NADH and FADH\[_2\]) from other steps of cellular respiration transfer their electrons to molecules near the beginning of the transport chain. In the process, they turn back into NAD\[^+\] and FAD, which can be reused in other steps of cellular respiration. Electron transfer and proton pumping. As electrons are passed down the chain, they move from a higher to a lower energy level, releasing energy. Some of the energy is used to pump H\[^+\] ions, moving them out of the matrix and into the intermembrane space. This pumping establishes an electrochemical gradient. Splitting of oxygen to form water. At the end of the electron transport chain, electrons are transferred to molecular oxygen, which splits in half and takes up H\[^+\] to form water. Gradient-driven synthesis of ATP. As H\[^+\] ions flow down their gradient and back into the matrix, they pass through an enzyme called ATP synthase, which harnesses the flow of protons to synthesize ATP.  NADH is very good at donating electrons in redox reactions (that is, its electrons are at a high energy level), so it can transfer its electrons directly to complex I, turning back into NAD\[^+\]. As electrons move through complex I in a series of redox reactions, energy is released, and the complex uses this energy to pump protons from the matrix into the intermembrane space. FADH\[_2\] is not as good at donating electrons as NADH (that is, its electrons are at a lower energy level), so it cannot transfer its electrons to complex I. Instead, it feeds them into the transport chain through complex II, which does not pump protons across the membrane.  Both complex I and complex II pass their electrons to a small, mobile electron carrier called ubiquinone (Q), which is reduced to form QH\[_2\] and travels through the membrane, delivering the electrons to complex III. As electrons move through complex III, more H\[^+\] ions are pumped across the membrane, and the electrons are ultimately delivered to another mobile carrier called cytochrome C (cyt C). Cyt C carries the electrons to complex IV, where a final batch of H\[^+\] ions is pumped across the membrane. Complex IV passes the electrons to O\[_2\], which splits into two oxygen atoms and accepts protons from the matrix to form water. Four electrons are required to reduce each molecule of O\[_2\], and two water molecules are formed in the process.  Chemiosmotic Coupling The energy-yielding reactions of electron transport are coupled to the generation of a proton gradient across the inner mitochondrial membrane. The potential energy stored in this gradient is harvested by a fifth protein complex, ATP synthase, which couples ATP synthesis to the energetically favorable return of protons to the mitochondrial matrix.  What does the Electron Transport Chain Do The electron transport chain has two essential functions in the cell: Regeneration of electron carriers: Reduced electron carriers NADH and FADH2 pass their electrons to the chain, turning them back into NAD+ and FAD. This function is vital because the oxidized forms are reused in glycolysis and the citric acid cycle (Krebs cycle) during cellular respiration. Generating proton gradient: The transport of electron through the chain results in a gradient of a proton across the inner membrane of mitochondria, later used in ATP synthesis. 6O2 + C6H12O6 + 38 ADP + 39Pi → 38 ATP + 6CO2 + 6H2O Fatty acid entry into mitochondria via the acylcarnitine/carnitine transporter