Online Lesson 1: Introduction to Metabolism and Biochemical Reactions PDF

Online Lesson 1 Introduction to Metabolism and Biochemical Reactions  Lesson Outcomes By the end of this lesson, you should be able to: – Explain how metabolic pathways are organized and regulated within a living cell. – Compare autotrophs and heterotrophs, aerobic and a...

Online Lesson 1 Introduction to Metabolism and Biochemical Reactions  Lesson Outcomes By the end of this lesson, you should be able to: – Explain how metabolic pathways are organized and regulated within a living cell. – Compare autotrophs and heterotrophs, aerobic and anaerobic organisms. – Compare nucleophilic substitutions, nucleophilic additions, carbonyl condensations, eliminations, and oxidations and reductions biochemical reactions. 2  Introduction to Metabolism Metabolism describes all biochemical reactions in living cells. Catabolism pathways are the sum of all metabolic processes by which complex molecules are broken down to simpler ones. Catabolism is generally accompanied by the net release of chemical energy. 3  Introduction to Metabolism (Cont.) Anabolism pathways are the sum of all metabolic processes by which complex molecules are built up from simpler ones. Anabolism is generally accompanied by the consumption of chemical energy. Metabolites are small molecules of (intermediates and metabolism products) that serve as intermediates in catabolic and anabolic pathways. 4  Introduction to Metabolism (Cont.) Catabolic and anabolic pathways stages are numbered and colored Catabolic pathways are in red, anabolic pathways are in blue. Appling, Dean, R. et al. Biochemistry: Concepts and Connections. (2nd Edition), 2018. 5  Introduction to Metabolism (Cont.) Most organisms get raw materials and the energy for biosynthesis from organic molecules such as glucose. Organisms can make a living, based on the source of their energy molecules, in two different ways: – Autotrophs – Heterotrophs 6  Introduction to Metabolism (Cont.) Autotrophs (self-feeding): – Synthesize glucose and all their other organic compounds from inorganic carbon, supplied as carbon dioxide. E.g., plants. Heterotrophs (feeding on others): – Synthesize their organic metabolites only by consuming other organic compounds. E.g., animals. 7  Introduction to Metabolism (Cont.) Almost all multicellular organisms and many bacteria are aerobic organisms. Aerobic organisms depend on cellular respiration process. Cellular respiration is a process that generate cellular energy by oxidizing nutrient molecules using O2 as the electron acceptor. 8  Introduction to Metabolism (Cont.) Some microorganisms can or must grow in anaerobic environments. Anaerobic environments refers to the absence of oxygen or the absence of a need for oxygen. Any biological processes that must or can occur without oxygen are called anaerobic process. 9  Introduction to Metabolism (Cont.) Glycolysis: – A catabolic pathway that converts a glucose into two pyruvate molecules and energy in both aerobic and anaerobic cells. The main input to glycolysis process is glucose, and it comes either from polysaccharides or dietary carbohydrates. – In the absence of oxygen, pyruvate is reduced to lactate or ethanol and CO2 molecules by anaerobic processes called fermentations. 10  Introduction to Metabolism (Cont.) Oxidative metabolisms: – When oxygen is present, pyruvate undergoes oxidative metabolism (respiration) where pyruvate is oxidized to acetyl-coenzyme A (acetyl-CoA). – Acetyl-CoA undergoes oxidation in the citric acid cycle. Citric acid cycle may also accept acetyl-CoA from lipids or proteins to completes the oxidative metabolisms. 11  Introduction to Metabolism (Cont.) Citric acid cycle: – Oxidation reaction of citric acid cycle produces reduced electron carriers. Examples of high energy electron carriers: – Nicotinamide adenine dinucleotide (NAD+) – Flavin adenine dinucleotide (FAD) – Electron carriers can be reoxidized to synthesis adenosine triphosphate (ATP) from adenosine diphosphate (ADP+). 12  Introduction to Metabolism (Cont.) Electron transport chain: – A sequence of electron carrier molecules in a cell where electrons pass from one carrier to the next. – The chain captures the energy released when high energy electron carrier molecules are oxidized – The energy is used to synthesis ATP. 13  Introduction to Metabolism (Cont.) Phosphorylation: adding phosphate group – The phosphorylation of adenosine diphosphate (ADP+) to adenosine triphosphate (ATP). – It occurs in conjunction with the flow of electrons in the electron transport chain of the inner mitochondrial membrane. 14  Introduction to Metabolism (Cont.) Gluconeogenesis: – A process by which glucose is synthesized from noncarbohydrate precursors – Examples of noncarbohydrate precursors are: Glycerol Lactate Some amino acids Acetyl-CoA (in plants) 15  Introduction to Metabolism (Cont.) Photosynthesis: – A process by which energy from light is captured by green plants and used to synthesis carbohydrate from CO2 and H2O. – The light energy is used to produce energy (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH). – Both ATP and NADPH are used for carbohydrate synthesis as a source of energy. 16 Types of Biochemical Reactions The five types of chemical reactions commonly found in cells and catalyzed by cellular enzymes are: – Nucleophilic substitution reactions – Nucleophilic addition reactions – Carbonyl condensation reactions – Elimination reactions – Oxidation/reduction reactions 17 Types of Biochemical Reactions (Cont.) Carbonyl group: – Most of biological reactions involve polar carbonyl group because most biological molecules contain one or more carbonyl groups. – The electron-poor C atom has a partial positive charge (δ+) and the electron-rich O atom has a partial negative charge (δ−). 18 Types of Biochemical Reactions (Cont.) Nucleophiles (Nu): – Are negatively polarized, electron-rich atoms that can form a bond by donating a pair of electrons to an electron-poor atoms. E.g., include hydroxide ion, alkoxides, or ionized carboxylates, thiolates, carbanions, deprotonated amines, and the imidazole side chain of histidine. 19 Types of Biochemical Reactions (Cont.) Electrophiles: – Are positively polarized, electron-poor atoms that can form a bond by accepting a pair of electrons from an electron-rich atoms. E.g., includes protonated imines, phosphate groups, and protons. Appling, Dean, R. et al. Biochemistry: Concepts and Connections. (2nd Edition), 2018. 20 Types of Biochemical Reactions (Cont.) Nucleophilic substitution reaction: One nucleophile replaces a second nucleophile. The best leaving nucleophilic groups are those that are stable as anions. Halides (e.g., CL−, Br−, and I−) and the conjugate bases of strong acids (e.g., PO43−) are good leaving groups 21 Types of Biochemical Reactions (Cont.) Nucleophilic addition reactions: – The addition of nucleophilic atoms to carbonyl carbon of aldehydes and ketones. – Carbonyl carbon in aldehydes and ketones is bonded to C and H atoms that are not best leaving nucleophilic groups. – Carbonyl groups typically undergo nucleophilic addition reactions instead of substitution reactions. 22 Types of Biochemical Reactions (Cont.) Carbonyl condensation reactions: – Forms new C-C bond between a carbonyl carbon of one reactant and the α carbon of another carbonyl molecule. – If the second carbonyl is an aldehyde or ketone, the reaction is called an aldol condensation. If the second carbonyl is an ester, then the reaction is called a Claisen condensation. 23 Types of Biochemical Reactions (Cont.) Elimination reactions: – The removal of two atoms (substitutes) from a molecule to form a C=C bond. – The most common elimination mechanism involves a carbanion intermediate produced by the lose of OH− to form the C-C double bond (where X=OH). Appling, Dean, R. et al. Biochemistry: Concepts and Connections. (2nd Edition), 2018. 24 Types of Biochemical Reactions (Cont.) Oxidation-reduction (redox) reactions: – Energy producing reactions in most cells involving oxidation of energy molecules like glucose. – A reversible electron transfer reaction from an electron donor (the reductant) to an electron acceptor (the oxidant). 25  Metabolic Control Mechanisms Living cell uses different metabolic control mechanisms, and these includes: – Control of enzyme level – Control of enzyme activity: Substance concentration Allosteric control Covalent modification of enzymes – Compartmentation – Hormonal regulation 26  Metabolic Control Mechanisms (Cont.) Control of enzyme level: – Enzyme levels in a cell may change in response to changes in metabolic needs. – Enzyme induction: the synthesis of an enzyme increases in a response to the appearance of its substrate. – Enzyme repression: the termination of enzyme synthesis in a response to the presence of end products of a metabolism. 27  Metabolic Control Mechanisms (Cont.) Substance concentration: – Substrates are usually present within cells at concentrations lower than the KM values for the enzymes that act on them. – KM (Michaelis constant) value refers to the concentration substrate at which half of the enzyme active sites are saturated. – This means, reaction velocities respond to small changes in substrate concentration. 28  Metabolic Control Mechanisms (Cont.) ​Substances that block enzyme activity are called inhibitors. – Competitive inhibitors are shaped such that they fit into an enzyme’s active site and prevent the normal substrate from binding. Permanent inhibitors results in permanent loss of enzymatic activity Reversible inhibitors cannot cause permanent loss of enzymatic activity and can be overcome by an increase in the [substrate molecules]. 29  Metabolic Control Mechanisms (Cont.) ​Competitive inhibition of enzyme activity: 30  Metabolic Control Mechanisms (Cont.) ​Reversible inhibition of enzyme activity: 31  Metabolic Control Mechanisms (Cont.) Non-competitive inhibitors: – Do not attach to the active site but instead bind to an allosteric site on the enzyme. – Alters the shape of the active site so that enzymatic activity is reduced or blocked completely. – Some enzymes have some inhibitory sites and activation sites to regulate enzyme function precisely. 32  Metabolic Control Mechanisms (Cont.) Allosteric site control: – An enzyme can be activated or inhibited by binding to allosteric effectors at allosteric site of an enzyme. – Allosteric sites are a region on enzyme that are located away from the active site of the enzyme. – The binding of allosteric effectors to an allosteric site causes the enzyme’s active site to change shape and become active. 33  Metabolic Control Mechanisms (Cont.) Covalent modification of enzymes: – Covalent modification of enzyme is the addition or removal of atoms or molecules from or to the enzymes one or more amino acids. – The addition or removal of atoms or molecules regulate the enzyme activity. 34  Metabolic Control Mechanisms (Cont.) Covalent modification of enzymes: – Phosphorylation or dephosphorylation: the addition or removal of a phosphate group. – Adenylylation: the transfer of an adenylate from ATP. – ADP-ribosylation: the transfer of an ADP- ribosyl from NAD+. – Acetylation: the transfer of an acetyl group from acetyl-coenzyme A. 35  Metabolic Control Mechanisms (Cont.) Compartmentation: division of labor – Enzymes that participate in the same metabolic mechanisms are localized to a particular compartment within the cell. – For example, RNA polymerases are found in the nucleus and nucleolus, where DNA transcription occurs, Enzymes of the citric acid cycle are all found in mitochondria where citric acid cycle occurs. 36 Compartmentation: Division of Labor Appling, Dean, R. et al. Biochemistry: Concepts and Connections. (2nd Edition), 2018. 37  Metabolic Control Mechanisms (Cont.) Hormonal regulation: – Are mechanisms that dispatch messages to regulate metabolic mechanisms. – The process of transmitting and receiving such messages and then responding with metabolic changes is called signal transduction. Hormones are one type of messengers that interact with specific receptors to cause specific metabolic changes in the target cell. 38  Reference Appling D. R., Anthony-cahill S. J., & Mathews C. K. (2018). Biochemistry: Concepts and Connections. 39