Introduction To Metabolism PDF

INTRODUCTION TO METABOLISM Objectives u Metabolism u Catabolic and anabolic pathways in cell metabolism u Principles of metabolic reactions u Activated carriers in the metabolism u Types of reactions in the metabolism u Regulation of metabolism u Summary 3 Metabolism A ——> B ——> C ——> D ——> E u The...

INTRODUCTION TO METABOLISM Objectives u Metabolism u Catabolic and anabolic pathways in cell metabolism u Principles of metabolic reactions u Activated carriers in the metabolism u Types of reactions in the metabolism u Regulation of metabolism u Summary 3 Metabolism A ——> B ——> C ——> D ——> E u The sum of all the chemical processes occurring in an organism at one time u Highly coordinated cellular activity. u Metabolism performs 4 functions; 1. Obtain energy for the cell. 2. Convert nutrients into macromolecules. 3. Assemble macromolecules into cellular structures. 4. Degrade macromolecules as required for biological function. Metabolites: Small molecule intermediate products in the degradation and synthesis of macromolecules Metabolism u Enzymes: Basic units of metabolism. u Substrates of these enzymes are called metabolites. u A metabolic pathway is a series of connected enzymatic reactions that produce a specific product. u Metabolic pathways consist of sequential steps. u There are more than 2,000 metabolic reactions, each catalyzed by a distinct enzyme. Metabolism: Catabolism vs Anabolism u Catabolism: Degradation pathways to salvage components and energy from biomolecules such as nucleotides, proteins, lipids and polysaccharides. Generates energy. u Anabolism: Biosynthesis of biomolecules such as nucleotides, proteins, lipids and polysaccharides from simple precursor molecules. Requires energy. u Biomolecules are composed predominantly of carbon, hydrogen, oxygen and nitrogen. Catabolism vs Anabolism Catabolism and anabolism are tightly linked together by their coordinated energy requirements: catabolic processes release the energy from food and collect it in the ATP; anabolic processes use the free energy stored in ATP to perform work. Stages of metabolism Catabolism Stage I. Breakdown of macromolecules (proteins, carbohydrates and lipids) to respective building blocks. Stage II. Amino acids, fatty acids and glucose are oxidized to a common metabolite (acetyl CoA) Stage III. Acetyl CoA is oxidized in citric acid cycle to CO2 and water. As result reduced cofactor, NADH2 and FADH2, are formed which give up their electrons. Electrons are transported via the tissue respiratory chain and released energy is coupled directly to ATP synthesis. Catabolic Pathways u Pathways that release energy by breaking down complex molecules into simpler compounds Principles of Metabolic Pathways 1. Metabolic pathways are irreversible u Metabolic pathways are highly exergonic which gives the pathway direction. Consequently if two metabolites are interconvertible, the pathway from the first to the second must be different than the pathway of the second back to the first. This independent interconversion allows the two pathways to be independently regulated. 2. Every metabolic pathway has a first committed step u Most of the reactions in a metabolic pathway are close to equilibrium, but every pathway has an irreversible highly exergonic reaction that commits the intermediate it produces to continue down the pathway. Principles of Metabolic Pathways-2 3. All metabolic pathways are regulated u The control of the metabolic flux of metabolites through a pathway is accomplished by regulating the rate limiting step of the pathway which often is the first committed step of the pathway. 4. Metabolic pathways in eukaryotes occur in specific cellular locations. Compartmentation of metabolic processes Metabolic Functions of Eukaryotic Organelles 16 ATP is the “universal energy currency” of the cell. u ATP is similar to the money kept in a wallet (and like money is often spent very quickly.) u When it is gone we have to replenish it. Sometimes we have a savings account or find an ATM nearby from which we can rejuvenate our wallets (e.g., creatine phosphate) u Occasionally, we need to break a bond, which takes longer. This is analogous to waiting for metabolism to regenerate our ATP. u 17 Other high energy storage compounds DG u The higher the G the more unstable the system u A change in free energy can occur with metabolism u u Exergonic: reactions that lose energy; -DG u Endergonic: reactions that gain energy; + DG u Metabolic reactions are often coupled where an exergonic reaction fuels an endergonic reaction When reactions go to equilibrium, DG = 0 no work can be done (therefore metabolic reactions do not usually reach an equilibrium) 19 u When we eat food, we ingest reduced carbon atoms. u During metabolism we oxidize these carbons to CO2, releasing potential energy of these foods. u In addition to energy-carrying molecules, we need other molecules to carry electrons. u NADH and FADH2 u Nicotinamide adenine dinucleotide (NADH) is a major electron carrier, reduced during oxidation of fuel molecules. u Oxidized form: NAD+ u Reduced form: NADH 20 FADH2 u Flavin adenine dinucleotide (FAD) is another key electron carrier. u Oxidized form: FAD u Reduced form: FADH2 21 Types of Chemical Reactions in Metabolism Oxidation-Reduction Reactions SH2 + NAD+ + H2O ——> S + NADH + H3O+ SH2: Reduced Substrate S: Oxidized Product NAD+: Electron Acceptor Group Transfer Reactions Y: + A—X Y—A + X: Phosphoryl Group Transfer CH2OH O HO OH OH OH a-D-glucose (Glc) ADP ATP Mg2+ CH 2OPO3= O HO OH OH OH a-D-glucose–6–P (G6P) Isomerization Reactions (Intramolecular Hydrogen Shifts) Aldose H Ketose H O C B: H C O H B: + H O + C R C O H C BH O H R R H C O C O H BH C R O H Rearrangements (altered carbon skeletons) C C C C C C C C Making C-C Bonds CoASH O CH3 C S CoA Acetyl–SCoA + O C COOH H2C COOH Oxaloacetate HO Citrate Synthase H2C COOH C COOH H2C COOH Citrate Breaking C-C Bonds CH2 OPO3 2– C O HO C H H C OH H C OH Aldolase CH2 OPO3 2– a–D–fructose-1,6-bisphosphate (FBP) CH2 OH CHO CHOH + C O CH2 OPO3 = CH2 OPO3 = Glyceraldehyde–3–P [GA3P] Dihydroxyacetone–P [DHAP] Metabolic Pathways Are Regulated Metabolism is highly regulated to permit organisms to respond to changing conditions Most pathways are irreversible Flux - flow of material through a metabolic pathway which depends upon: (1) Supply of substrates (2) Removal of products (3) Enzyme activities Levels of Metabolism Regulation 1. Nervous system. 2. Endocrine system. 3. Interaction between organs. 4. Cell (membrane) level. 5. Molecular level Feedback inhibition Product of a pathway controls the rate of its own synthesis by inhibiting an early step (usually the first “committed” step (unique to the pathway) Feed-forward activation Metabolite early in the pathway activates an enzyme further down the pathway