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Metabolism The total reaction of the cell in which the enzymes participate to exchange matter and energy between the cell and its environment . -In order to stay a life the cell should keep an energy supply for the essential metabolic activities .There are thousands of chemical reactions taking place with the cell and out of the cell in order to perform certain function .These reactions involved as exchange of the matter and energy .This energy is either utilized or evolved. -These chemical reaction can involve: Oxidation,Reduction,Hydroxylation,Carboxylation, Condensation, all of them are catalyzed by enzymes -So as a result of metabolism we have energy production,e.g In oxidation of protein. Function of Metabolism 1-Energy production, e.g The oxidation of protein, F.A, Glucose, Acetyl-CO-A is formed, enter the pathways of produce energy, but when energy production inhibited, death occur. 2. Building units production, e,g. amino acid, F.A. & simple they important for building new structure because of the continuous breakdown of the body tissues which must be replaced. 3.The synth. of protein: from the amino acids , lipids from F.A., nuclic acid (N.A.) from purine, pyrmidine. 4. Special cellular function molecules, e.g. mitochondria, in the cell membrane (phospho-lipids) are important in the permeability of the cell membrane, polysaccharides are import in the cell – cell recognition. *sources of energy: the main source is the sun light usually plants take the sun light with CO2 + H2O to produce glucose. - The metabolism can be classified into tow types:1. Catabolism. 2. Anabolism. * Catabolism (catabolic metabolism): Degradation or the breakdown of the large molecules into simple ones. - Catabolism has 3 stages:a- Conversion to building units.e.g. Polysacch. --------- Hexoces (6C) or Pentose (5C) Lipids F.A. + glycerol Protein A.A. b- The formation of acetyl-co-A: The conversion of all these substances (hexoses, pentoses, F.A., A.A.) into 2 carbon compound which is Acetyl-CO-A which is common among all these nutrients. c. Oxidation of the Acetyl-CO-A into Co2 + H2O. the energy is produced as (ATP) in krebs TcA cycle. * These catabolic stages are all associated with the liberation of energy. The energy produced takes place in the catabolism. *Anabolism: The process of biosynthesis & collection of small molecule & synthesis of large ones (condensation of small molecule). It is the reverse of catabolism. Ctab. Large small Anab. Small large a.a protein F.A. + glycerol fats (Triglyceride) * Anabolism is characterized by the use of the energy produced by catabolism. i.e, (ATP) is produced by catabolism & utilized by anabolism. * The two processes occur at the same time but in different compartment – Anabo. in cytoplasm – catab. in mitochondria. e.g. F.A. oxidation in the mitochondria. F.A. synthesis in the cytoplasm. * Note: The same enzyme catalyzed the catabolism & the anabolism. e.g. Glucose E1 pyruvate E2 lactic acid. This process is called (glycolysis). While Lactic acid E3 pyruvate E4 glucose. This process is called (glyconeogenesis). e.g. glycogen lactic acid need 12 enzymes. Lactic glycogen needs 9 enzymes. * The catabolism & the anabolism can not catalyzed by the same enzymes because:1. They occur at the same time. 2. One of them involves ATP production & the other ATP utilization. Catabolism involves energy production. Anabolism involves energy reduction. * Catabolism & anabolism could be represented as a tree Polysacch. Protein Glucose A.A. Lipid F.A.+ glycerol Acetyl – CO – A H2O CO2 ATP * The types of the energy which are involved in metabolism:1. Potential energy: energy stored in the organ molecules Sun light Glucose, Lipid, proteins CO2 + H2O + Energy. [o] 2. Free energy: energy which can do work at a constant temp. & pressure. * In any living organism - Isothermal: no heat is used for doing work. - Use the chemical energy (energy stored in ATP molecule). * ATP is synthesized from the phosphorelation of ADP. This occurs with the oxidation reactions: ATP formation:ADP + Pi ATP - Enzyme reaction couples oxidation reactions. * When the ATP is formed it will diffuse from the site of production to the sites of utilization in the cell. ATP energy is transferred to an acceptor molecule & used when needed. Electron transfer system:One of the systems (in respiratory chain) transferring the energy from catabolic process to anabolic process & usually Co-enzymes such as NADP is needed for this processes. NADP + H NADPH Energy is produced as a result of transfer of this electrons at the presence of these enzyme. Metabolic turnover:Continuous synth. & degradation of tissue or nutrients to keep a constant conc. of the cell constituent. In the cell there are different organelles & enzymes when there is any process( metabolic process). There is a utilization of material & breakdown of cells in contact with the process. these damaged cells are replaced.e.g. in any enzymatic reaction the enzymes are exhausted , this exhaustion renders the enzyme inactive, so the body needed new enzymes , as a result there is always inactivation or activation of the enzymes. All the damage cells will be replaced so that to keep same conc. of the cell constitutes const. *This turnover varies from one organ to another , e.g. in the liver & intestine is more rapid than the other tissues, because: many exogenous compound come to the liver or intestine where it is detoxified [function of the liver the detoxification of the exogenous toxic materials] so the enzymes which are present in them are more active & are damaged & replaced very rapidly, i.e. turnover (metabolic turnover) is high which in less active tissues, such as lipid the turnover is slow. The Metabolism This is done by: 1. Identification of chemical path way. - Identification of each product - Identification of each enzyme. 2. The regularity mechanism of the reaction rate to specify which enzyme is a regulatory one. If the whole seq. Contain 10 enzymes, three enzymes of them are regulatory, all are not affected except the 3 enzymes. The 3 enzymes are regulatory when there is an accumulation of the produced the rate of the enzymes are reduced & the 3 enzymes rate increase. In the diabetes mellitus (un controlled) - The glucose pathway becomes the minor. - The fat pathway becomes the major. Fat produces more acetyl COA, this acetyl COA will be in excess of kribs cycle capacity, some of them go to the formation of keton bodies (acetone bodies). * Normally these K.b. are not present or little. - Amount of CO2 in glucose production will be less in diabetic person. Glucose [O] CO2 F.A oxidation K.B. (decrease) (increase) Accumulation Certain type of a.a., tyrosine & phenyl alanin. Produce keton bodies, so we call it (ketogenic a.a.) Tyrosine & phenyl alanin produce AC.AC (K.B) Inhibitors: It has been found when fluorocitrate is present. It will inhibit citric acid cycle (C.A. oxidation) Fluorocitrate citric acid accumulation Acetoacetate Cellular regulation of the metabolic pathway: Rate of cellular Catabolism (cata.) cellular need of energy (E) If cellular need of E , rate of cata. Changes every second (occurs instantly) also the need of intermediates in the cell & the rate of biosynth. When there is enough intermediate biosynth. When intermediates go short the rate & biosynth de There is balance between E need & the rate of cata. Level of regulation: 1.Reactants & products: enzyme kinetic activity depend on: - pH - Substrate conc. - Product conc. - Co – enz. * In living sys. usually PH & Co – enz. Constant. 2.Regulatory enzyme: When accumulation of end product give signal to enzyme to (a feed back inhibition) or it could be stimulated when there is excess metabolitic. * So, inhibition by the end product or stimulation by special metabolite. 3. Genetic control of enzyme synth:Concentrate of active from of enzyme balance between synth. & degradation. * Enzyme synth. Is controlled by genes in the DNA. 4. Hormonal control: This is important in the high multicellular organism. Insulin deficiency a. failure of glucose transport across the cell. b. FA synth. c. KB ketone body synth. * The rate of Rx. is change according to type of hormone which is stimulated. CHO Metabolism: CHO is a type of compound contain C, H2, O2 {H2 , O2} in the same ratio that as water could be classified to: Simple sugars: glucose, fructose, galactose, (( Monosacch. )) ribose Disacch.: Sucrose. Glu. + Fru. Lactose Glu. + Gala. Maltose Glu. + Glu. Formed from hydrolysis of starch Polysacch.: starch, cellulose, glycogen. In dief. the most common one is starch, which comes next glu, fru., gala. ** Lactose present in milk. Digestion: Mouth Starch contain many glu.units Salivary amylase amylopectin + amylose In starch: One chain connected to the other by 6 glycoside linkage * In the mouth starch is hydrolyzed by amylase enzyme to amylose & amylopectin (( 1,6 linkage is broken )) this hydrolysis taken place in mouth only.