INTRODUCTION TO METABOLISM

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METABOLISM1- Biochemistry (3rd Edition) 3rd Editionby Christopher K. Mathews , Kensal E. van Holde, Kevin G.Ahern2- Lehninger Principles of Biochemistry 4th Editionby David L. Nelson , Michael M. Cox3- Biochemistry: International Editionby Lubert Stryer , Jeremy M. Berg , John L. Tymoczko4- Textbook of Biochemistry With Clinical Correlations,Fourth Editionby Thomas M. DevlinAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

INTRODUCTION TOMETABOLISMANDSOME BIOENERGETICCONSIDRATIONAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Concepts Intermediary metabolism:all reactions concerned with storing andgenerating metabolic energy and with using thatenergy in biosynthesis of low molecular weightcompound and energy storage compounds( denovo protein and nucleic acid Not included)An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Energy metabolism:is that part of intermediary metabolismconsisting of pathways that store or generatemetabolic energy. Central pathways (of metabolism):are substantially the same pathways in manydifferent organisms, and they account for relativelylarge amounts of mass transfer and energygeneration within a cell; they are the quantitativelymajor pathways.An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

All multicellular organisms and many bacteria areaerobic organisms; they depend absolutely uponrespiration, the coupling of energy generation tothe oxidation of nutrients by oxygen. metabolite ( noun ) : substance undergoingchange during metabolism, are theintermediates and products of metabolism Oxidation and Reduction in Organic Chemistry A reduction will result in a net increase in thenumber of C-H bonds, or a net decrease in thenumber of C-O bonds (or equivalent, such as C-Cl,C-Br, etc). An oxidation will result in a net decrease in thenumber of C-H bonds, or a net increase in thenumber of C-O bonds (or equivalent).An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

PYRUVATEAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.ETHANOL

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FREE WAYS ON THE METABOLIC ROADMAPAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

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CENTRAL PATHWAYS OF ENERGYMETABOLISM Glycolysis (glucose)pyruvate Fermentation (anaerobic) pyruvateethanol Oxidative metabolism-respiration- (aerobic)pyruvateacetyl-coenzyme Aβ-oxidation of fatty acidsome amino acidsanabolic directionCITRIC ACID CYCLE (CAC) In aerobic all catabolic pathways converge on the CAC oxidative reactions of CAC generate reduced electroncarriers whose re-oxidation derives ATPbiosynthesis.(through e-transport& oxidative phosphorylation)An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

DISTINCT PATHWAY FORBIOSYNTHESIS AND DEGRDATION i.e. fatty acid synthesis takes place in cytosol, bydistinct mechanisms and different enzymes thanfatty acid oxidation which occur in mitochonderia Reasons :1. Exergonicity & endergonicity (of each pathway)2. Need to control the flow of metabolites inrelation to the bio-energetic status a cellEx: futile cycleregulationsubstrate cycleAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Bio-energetic considerations Oxidation as metabolic energy BIOLOGICAL OXIDATIONS are oxidation reactionsoccur without a large increase in temperature and withcapture of some of the free energy as chemical energy.- Metabolic energy capture occurs largely through thesynthesis of ATP, a molecule designed to provide energy forbiological work. The capture of energy is quite efficient.- i.e : catabolism of glucose, for example, about 40% of the2870 kJ/mol of energy released is used to drive the synthesisof ATP from ADP and Pi.An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

More highly reduced a substrate , the higher itspotential for generating biological energy Biological energy is used for1- countless reaction2- transport materials across membranes3- transmit nerve impulses4- contract musclesAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Important Points about G1. Three important terms relating to the free energychange of a process are:a- G - the total free energy change for a reaction under anyconditionsb- G - free energy under standard conditions (all concentrationsof 1M)c- G - the free energy change under standard biologicalconditions (all concentrations 1M, [H2O] constant, and pH 7.0)Thus, a positive may influence a reaction, but cellular conditionsmay make the overall for the reaction negative.2. G and only G determines whether a reaction is favorable aswritten. Only when is negative is a reaction favored. The sign of G or G does not determine the direction a reaction will proceed.3. G depends on temperature ( G H - T S). This can be a factorfor a given reaction occurring in different organisms living under verydifferent conditions of temperature.An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Energetic BiomoleculesAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

HYDROLYSIS REACTIONS FOR SOMEBIOCHEMICALLY IMPORTANT PHOSPHATECOMPOUNDS ﺟﺰﻳﺋﺎت طﺎﻗوﻳﺔ .wmf - Shortcut.lnkAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

(ATP) Adenosine Tri Phosphate:An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

ATP as Free Energy Currency thermodynamically unstable compound used to provide energy in a wide variety of metabolicreactions Hydrolysis of either phosphoanhydride bond in ATP hasa G of about -31 kJ/mol. ATP breakdown is usually coupled withthermodynamically unfavorable reaction. ATP has a high "phosphoryl group transfer potential"rather than calling it a high energy compound. ATP hydrolysis under cellular conditions yields ADP Pior AMP PPi. Effective G' values in cells may be close to -50 kJ/molAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Energy Yields, respiratory Quotients,and Reducing Equivalents More highly reduced a substrate , the higher its potential forgenerating biological energyFat has higher caloric content than carbohydrateC6H12O6 6O26CO2 6H2O G -3.74 kcal/g RQ 1 (mol CO2/mol of O2)C16H32O2 23O2RQ 0.7 (why?)16CO2 6H2O G - 9.30kcal/g Reducing equivalent: express degree of substratemole of H atom)NAD , NADP reductive biosynthesis)An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.oxidation (1NADH, NADPH (major source for

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CARBOHYDRATEMETABOLISMANAEROBIC PROCESSESAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Glycolysis Earliast metabolic pathwayUniversal in living cellsRegulation of glycolysis is well understoodThe central metabolic role this pathway plays ingenerating both energy and metabolicintermediates for other pathwaysAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

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Summary of Glycolysis Glycolysis is a central metabolic pathway involvingmetabolism of the sugar glucose Divided into a phase in which ATP energy is investedand a phase in which ATP energy is generated The starting point for glycolysis is the moleculeglucose and the process ends with formation of twopyruvate molecules Additional products of glycolysis include two ATPsand two NADHs.An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

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Reaction 1An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Reaction 2: isomerizationAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Reaction 3: phosphorylationAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Reaction 4: cleavageAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Reaction 5: isomerizationAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

nd2An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.phase

Reaction 6: oxidationAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Reaction pathway for glyceraldehyde-3-phosphate dehydrogenaseAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Reaction 7: substrate levelphosphorylationAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Reaction 8: shift of phosphorylgroupAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Reaction 9: dehydrationAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Reaction 10: substrate levelphosphorylationAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

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Strategy of glycolysis1. The process of glycolysis requires ATP energy inputbefore ATP and NADH energy can be released. Thisbreaks glycolysis into two phases - an energy inputphase (reactions 1-5) and an energy release phase(reactions 6-10). The energy input phase includes tworeactions (hexokinase and phosphofructokinase),each where ATP is used.An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

2. Glycolysis, through the formation of pyruvate,includes a single oxidation step:D-Glyceraldehyde-3-Phosphate NAD Pi 1,3Bisphosphoglycerate NADH H Because there are two molecules of G3P permolecule of glucose, there is a total of twomolecules of NADH formed per molecule of glucose.An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

3. 1,3BPG and PEP are phosphorylated compounds,each with a phosphoryl group that has a free energyhigher than that of the phosphate on ADP. Thus1,3BPG and PEP can transfer a phosphoryl group toADP to form ATP. This is called substrate levelphosphorylation and it yields four molecules of ATPper molecule of glucose in the energy releasing phaseof glycolysis. Thus, the 10 reactions of glycolysisgenerate two net molecules of ATP per molecule ofglucose.An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

METABOLIC FATES OF PYRUVATE Under aerobic conditionspyruvate is transformed into acetyl-CoA, which thenenters the citric acid cycle. Under anaerobic conditions1. In animal cells and lactic acid bacteria, pyruvate isconverted to lactate. In this case, NADH addselectrons to pyruvate, forming NAD and lactate.Pyruvate NADH H Lactate NAD 2. Yeasts recycle NADH to NAD by alcoholicfermentation:Pyruvate - acetaldehyde - ethanol.An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

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Entry of Other Sugars intothe Glycolytic Pathway1. Monosaccharide Sugars Galactose, mannose, and fructose are the main sugarsof interest. All can be phosphorylated at position six byhexokinase and ATP (Note :fructose can enter the the glycolyticpathway as fructose-1-phosphate.Galactose can also be converted toglucose via theUDP-galactose-4-epimerase catalyzed pathway)2. Disaccharides The enzyme lactase breaks down the disaccharidelactose to yield the monosaccharides galactose andglucose. Maltase breaks down maltose to yield twomolecules of glucose. Sucrase breaks down sucrose toyield fructose and glucose. All of thesemonosaccharidessubsequently enter glycolysisAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

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Routes for utilizing substrates other than glucosein glycolysis.An evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

3. PolysaccharidesGlycogen (from animals), starch (e.g., amyloseand amylopectin from plants), and cellulose(from plants) Glycogen phosphorylase catalyzesphosphorolysis of glycogen to glucose-1phosphateAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

Glycerol Glycerol is a product of fat metabolism. It can beconverted to glycerol-3-phosphate in the liver byglycerol kinase. This reaction consumes onemolecule of ATP. Glycerol-3-phosphate is thenoxidized by glycerol-3-phosphate dehydrogenase todihydroxyacetone phosphate (DHAP), reducing onemolecule of NAD in the process. Once formed, DHAPcan enter glycolysisAn evaluation version of novaPDF was used to create this PDF file.Purchase a license to generate PDF files without this notice.

1- Biochemistry (3rd Edition) 3rd Edition by Christopher K. Mathews , Kensal E. van Holde, Kevin G. Ahern 2- Lehninger Principles of Biochemistry 4th Edition by David L. Nelson , Michael M. Cox 3- Biochemistry: International Edition by Lubert Stryer , Jeremy M. Berg , John L. Tymoczko 4- Textbook of Biochemistry With Clinical Correlations,

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