Chapter 17 Metabolism: An Overview PDF

Reginald H. Garrett Charles M. Grisham www.cengage.com/chemistry/garrett Chapter 17 Metabolism: An Overview © 2017 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 ser...

Reginald H. Garrett Charles M. Grisham www.cengage.com/chemistry/garrett Chapter 17 Metabolism: An Overview © 2017 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. Chapter 17 “All is flux, nothing stays still. Nothing endures but change.” Heraclitus c. 540 – 480 B.C. Metamorphosis of butterflies is a dramatic example of metabolic change. Essential Question What are the anabolic and catabolic processes that satisfy the metabolic needs of the cell? Outline 17.1 Is metabolism similar in different organisms? 17.2 What can be learned from metabolic maps? 17.3 How do anabolic and catabolic processes form the core of metabolic pathways? 17.4 What experiments can be used to elucidate metabolic pathways? 17.5 What can the metabolome tell us about a biological system? 17.6 What food substances form the basis of human nutrition? Metabolism Metabolism represents the sum of the chemical changes that convert nutrients, the “raw material” necessary to nourish living organisms, into the energy and the chemically complex finished products of cells. Metabolism consists of literally hundreds of enzymatic reactions organized into discrete pathways. 17.1 Is Metabolism Similar in Different Organisms? Organisms show remarkable similarity in their major metabolic pathways This is evidence that all life descended from a common ancestral form And yet, living things also exhibit metabolic diversity Note the classification of organisms in Table 17.1 Oxygen is essential for aerobes, but obligate anaerobes are poisoned by oxygen 17.1 Is Metabolism Similar in Different Organisms? Autotrophs use CO2; heterotrophs use organic carbon; phototrophs use light; chemotrophs use organic and inorganic electron donors Mindtap Role of Oxygen Can organisms use oxygen as an electron acceptor in energy-producing pathways? o Those that can…aerobes o Those that can survive without oxygen…anaerobes o Those that require oxygen…obligate aerobes (humans) o Those that can adapt to anaerobic conditions by substituting other electron acceptors for oxygen in their energy-producing pathways…facultative anaerobes (E. coli) o Those that cannot use oxygen at all and are even poisoned by it…obligate anaerobes (botulin toxin) 17.1 Is Metabolism Similar in Different Organisms, Con’t? The flow of energy in the biosphere and the carbon and oxygen cycles are intimately related The impetus driving the cycle is light energy Phototrophs use light to drive synthesis of organic molecules Heterotrophs use these as building blocks CO2, O2, and H2O are recycled See Figure 17.1 Flow of Energy in the Biosphere Is Coupled to the Carbon and Oxygen Cycles Outline 17.1 Is metabolism similar in different organisms? 17.2 What can be learned from metabolic maps? 17.3 How do anabolic and catabolic processes form the core of metabolic pathways? 17.4 What experiments can be used to elucidate metabolic pathways? 17.5 What can the metabolome tell us about a biological system? 17.6 What food substances form the basis of human nutrition? 17.2 What Can Be Learned From Metabolic Maps? Metabolism consists of catabolism and anabolism Catabolism: degradative pathways o Usually energy-yielding Anabolism: biosynthetic pathways o Usually energy-requiring Metabolic maps portray the principal reactions of intermediary metabolism When the major metabolic routes are known and their functions are understood, the maps become easy to follow, despite their complexity A Metabolic Map Figure 17.2 A metabolic map, indicating the reactions of intermediary metabolism and the enzymes that catalyze them. More than 500 different chemical intermediates, or metabolites, and a greater number of enzymes are represented here. 17.2 What Can Be Learned From Metabolic Maps? One interesting transformation of the metabolic map represents each intermediate as a black dot and each enzyme as a line In this way, more than a thousand enzymes and substrates are represented by just two symbols A dot connected to a single line must be a nutrient, a storage form, an end product, or an excretory product 17.2 What Can Be Learned From Metabolic Maps? A dot connected to just two lines is probably an intermediate in one pathway and has only one fate in metabolism A dot connected to three lines represents an intermediate that has two metabolic fates See Figure 17.3 and Table 17.2 17.2 What Can Be Learned From Metabolic Maps? 17.2 What Can Be Learned From Metabolic Maps? Figure 17.3 The metabolic map as a set of dots and lines. The heavy dots and lines trace the central energyreleasing pathways known as glycolysis and the citric acid cycle. Organization in Pathways Pathways consist of sequential steps The enzymes may be separate o Or may form a multienzyme complex o Or may be a membrane-bound system New research indicates that multienzyme complexes are more common than once thought Multienzyme Systems May Take Different Forms Figure 17.5 Schematic representation of types of multienzyme systems carrying out a metabolic pathway. (a) Physically separate, soluble enzymes with diffusing intermediates. (b) A multienzyme complex. Substrate enters the complex and becomes bound and then modified by E1 to E5. No intermediates are free to diffuse away. (c) A membrane-bound multienzyme system. Outline 17.1 Is metabolism similar in different organisms? 17.2 What can be learned from metabolic maps? 17.3 How do anabolic and catabolic processes form the core of metabolic pathways? 17.4 What experiments can be used to elucidate metabolic pathways? 17.5 What can the metabolome tell us about a biological system? 17.6 What food substances form the basis of human nutrition? How Do Anabolic & Catabolic Processes Form the Core of Metabolic Pathways? Catabolic pathways are characteristically energyyielding Anabolic pathways are characteristically energyrequiring Catabolism involves the oxidative degradation of complex nutrient molecules Anabolism is a synthetic process in which the varied and complex biomolecules are assembled from simpler precursors Figure 17.6 Anabolism and Catabolism Are Interrelated Products from one provide substrates for the other. Many intermediates are shared between anabolism and catabolism. Anabolism and Catabolism Are Not Mutually Exclusive Catabolic pathways converge to a few end products Anabolic pathways diverge to synthesize many biomolecules Some pathways serve both in catabolism and anabolism o Such pathways are amphibolic The Pathways of Catabolism Converge to a Few End Products Figure 17.7 The three stages of catabolism. Stage 1: Proteins, polysaccharides, and lipids are broken down into their component building blocks. Stage 2: The building blocks are degraded into a common product, the acetyl groups of acetyl-CoA. Stage 3: Catabolism converges to three principal end products: water, carbon dioxide, and ammonia. Comparing Pathways Anabolic and catabolic pathways involving the same product are not the same Some steps may be common to both Others must be different - to ensure that each pathway is spontaneous This also allows regulation mechanisms to turn one pathway on and the other off Cell Management of Metabolism 1. Tight and separate regulation 2. Competing pathways are isolated Isolation of Competing Pathways Isolating opposing pathways within distinct organelles avoids interference between them. Example: o The enzymes responsible for catabolism of fatty acids are localized within the mitochondria. o The enzymes responsible for fatty acid biosynthesis are found in the cytosol. Metabolic Regulation Requires Different Pathways for Oppositely Directed Metabolic Sequences Figure 17.8 Parallel pathways of catabolism and anabolism must differ in at least one metabolic step so that they can be regulated independently. Shown here are two possible arrangements of opposing catabolic and anabolic sequences between A and P. (a) Parallel sequences proceed by independent routes. (b) Only one reaction has two different enzymes. ATP Serves in a Cellular Energy Cycle ATP is the energy currency of cells Phototrophs transform light energy into the chemical energy of ATP In heterotrophs, catabolism produces ATP, which drives activities of cells ATP cycle carries energy from photosynthesis or catabolism to the energy-requiring processes of cells Figure 17.9 The ATP Cycle in Cells ATP is formed via photosynthesis in phototrophic cells or by catabolism in heterotrophic cells. Energy-requiring cellular activities are powered by ATP hydrolysis, liberating ADP and Pi. The Substrates of Catabolism Contain Relatively Reduced Forms of Carbon Figure 17.10 Comparison of the state of reduction of carbon atoms in biomolecules. Chains of -CH2- groups are the most energy-rich form of reduced carbon in the biosphere. Carbon dioxide is the final product of catabolism and the most oxidized form of carbon in the biosphere. NAD+ Collects Electrons Released in Catabolism The substrates of catabolism – proteins, carbohydrates, and lipids – are good sources of chemical energy because their carbon is reduced The oxidative reactions of catabolism release reducing equivalents from these substrates, often in the form of hydride ions These hydrides are transferred to nicotinamide adenine dinucleotide (NAD+) molecules, reducing them to NADH NADH in turn passes these reducing equivalents to other acceptors The ultimate oxidizing agent, O2, is the final acceptor of electrons, becoming reduced to H2O NAD+ Collects Electrons Released in Catabolism, Con’t Figure 17.11 Hydrogen and electrons released during oxidative catabolism are transferred as hydride ions to the pyridine nucleotide, NAD+, to form NADH + H+ in dehydrogenase reactions. NADPH Provides the Reducing Power for Anabolic Processes Whereas catabolism is oxidative, anabolism is reductive Biosynthesis typically relies on reducing equivalents from NADPH (reduced nicotinamide adenine dinucleotide phosphate) NADPH can be viewed as the carrier of electrons from catabolic reactions to anabolic reactions In photosynthesis, light energy is used to pull electrons from water and transfer them to NADP+ O2 is a by-product of this process The NADPH Cycle Figure 17.12 Transfer of reducing equivalents from catabolism to anabolism via the NADPH cycle. A Summary of Vitamins and Coenzymes Discussed Elsewhere in the Text Outline 17.1 Is metabolism similar in different organisms? 17.2 What can be learned from metabolic maps? 17.3 How do anabolic and catabolic processes form the core of metabolic pathways? 17.4 What experiments can be used to elucidate metabolic pathways? 17.5 What can the metabolome tell us about a biological system? 17.6 What food substances form the basis of human nutrition? 17.4 What Experiments Can Be Used to Elucidate Metabolic Pathways? Eduard Büchner (late 19th century) showed that fermentation of glucose in yeast cells yielded ethanol and carbon dioxide This led to a search for intermediates of glucose breakdown Metabolic inhibitors were important tools for elucidating the pathway steps Mutations were also used to create specific metabolic blocks Inhibitors Reveal the Sequence of Reactions in a Metabolic Pathway Figure 17.13 The use of inhibitors to reveal the sequence of reactions in a metabolic pathway. (a) Control. (b) Plus inhibitor. Intermediates upstream of the metabolic block (B, C, and D) accumulate, revealing themselves as intermediates in the pathway. The concentration of intermediates lying downstream (E and F) will fall. Isotopic Tracers Can Be Used as Metabolic Probes Metabolic pathways have been elucidated by use of isotopic forms of elements Metabolic substrates and intermediates can be “labeled” with a measurable isotope and then “traced” through a series of reactions Two types of isotopes have been used in this way o Radioactive isotopes, such as 14C and 32P o Stable “heavy” isotopes, such as 18O and 15N Using a Radioactive Isotope as a Metabolic Tracer Figure 17.14 One of the earliest experiments using a radioactive isotope as a metabolic tracer. Melvin Calvin found that 3-phosphoglycerate (PGA) is the first metabolite labeled when algae are incubated with radioactive CO2. NMR Spectroscopy Is a Noninvasive Metabolic Probe The nuclei of certain atomic isotopes have magnetic moments Such nuclei can absorb radio-frequency energy in the presence of a magnetic field at a unique resonant frequency The nuclear magnetic resonance (NMR) absorption of a nucleus is influenced in predictable ways by the chemical nature of its neighboring atoms and by its dynamic behavior (motion) For these reasons, NMR signals can provide a wide range of structural and dynamic information about biomolecules Metabolism Observed in Real Time with NMR Figure 17.15 The metabolism of a living subject can be observed in real time with NMR spectroscopy. Metabolic Pathways Are Compartmentalized Within Cells Figure 17.17 Compartmentalization of glycolysis, the citric acid cycle, and oxidative phosphorylation. Outline 17.1 Is metabolism similar in different organisms? 17.2 What can be learned from metabolic maps? 17.3 How do anabolic and catabolic processes form the core of metabolic pathways? 17.4 What experiments can be used to elucidate metabolic pathways? 17.5 What can the metabolome tell us about a biological system? 17.6 What food substances form the basis of human nutrition? 17.5 What Can the Metabolome Tell Us About a Biological System? The metabolome is the complete set of lowmolecular weight molecules present in an organism and excreted by it under a given set of circumstances Metabolomics is the systematic identification and quantitation of all these metabolites in each organism or sample Mass spectrometry (MS) and nuclear magnetic resonance (NMR) are both powerful techniques for metabolomic analysis 17.5 What Can the Metabolome Tell Us About a Biological System? Figure 17.18 The –omics of contemporary biochemistry and molecular biology, as it relates to metabolism. 17.5 What Can the Metabolome Tell Us About a Biological System? MS offers unmatched sensitivity for detection of metabolites at low concentrations NMR provides remarkable resolution and discrimination of metabolites in complex mixtures Mass Spectrometry Offers Remarkable Sensitivity for Metabolomic Analyses Mass spectrometry (MS) is the key tool in discovery metabolomics Technological innovations allow direct MS analysis of single bacterial colonies or very small tissue samples through microscopic interfaces Data sets can be extraordinarily complex Software can collate the MS information and create networks of structural similarities that lead to unambiguous identification of individual metabolites The MEDLIN repository lists about 250,000 metabolites and about 70,000 structures; see http://masspec.scripps.edu/ Mass Spectrometry Offers Remarkable Sensitivity for Metabolomic Analyses Analysis of urine samples from patients with inborn errors in metabolism. 17.5 What Can the Metabolome Tell Us About a Biological System? Figure 17.20 NMR provides remarkable resolution and discrimination of metabolites in complex mixtures. (a) One-dimensional NMR of 26 smallmolecule standards. (b) Two-dimensional NMR of the same set of standards overlaid on an aqueous extract of Arabidopsis Fluxomics The true phenotype of a cell depends not only on knowledge of all the metabolites in a cell at any given moment but also on information about the flow of metabolites through its metabolic network The quantitative study of metabolite flow, or flux, is termed fluxomics The fluxome is all the metabolic fluxes in a metabolic network It thus represents systems-level information on those cellular processes defined by the metabolic network The fluxome is a dynamic view of the metabolic processes in a cell or organism Outline 17.1 Is metabolism similar in different organisms? 17.2 What can be learned from metabolic maps? 17.3 How do anabolic and catabolic processes form the core of metabolic pathways? 17.4 What experiments can be used to elucidate metabolic pathways? 17.5 What can the metabolome tell us about a biological system? 17.6 What food substances form the basis of human nutrition? 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