Lecture'14'–'Chapter'15'Metabolism'1'Outline'- Metabolism'- ATP'as'the'universal'currency'of'free'energy'- Coupled'ReacBons'- AcBvated'carriers'- RegulaBon'of'metabolic'processes'2'What'is'Metabolism?'ATP' ADP'MoBon'AcBve'transport'Biosynthesis'(anabolism)'Signal'amplificaBon'Photosynthesis!(autotrophs)!OxidaBon'of'fuel'molecules'(catabolism)'(chemoheterotroph)'3'The'complex'of'physical'and'chemical'processes'occurring'within'a'living'cell'or'organism'that'are'necessary'for'the'maintenance'of'life.'Contain'potenBal'energy'that'can'be'released'by'oxidaBon'Hydrocarbon'Fuels'(fossil'fuel,'biofuel,'glucose)'~ 30 ATPs 6'CO2'6'H2O'C6H12O6'+'6'O2'−2880'kJ/'mol'6'CO2'6'H2O'4'Energy'is'released'from'glucose'in'a'stepwise'fashion,'forming'ATP'5'30\32'ATP'Free'Energy'Released'by'OxidaBon'of'single\carbon'compounds'6'Two'main'types'of'Cellular'Fuel'7'OxidaBon\ReducBon'reacBons':'Overview''Aox'''+'''Bred''''''''''''''''''''Ared''''+'''''Box'ReducBon'\\\''Gain'of'e\/loss'of'oxygen/gain'of'hydrogen'OxidaBon'\\\''Loss'of'e\/gain'of'oxygen/loss'of'hydrogen'8'NADH'NADH'Metabolism'e/!e/!e/!e/!e/!e/!e/!9'High'Enthalpy/Low'Entropy'(Higher'free'energy)'Low'Enthalpy/High'Entropy'(Lower'free'energy)'Catabolism'Anabolism'OxidaBon'of'carbon'fuel'NADH'NADH'FADH2'e/!10'The'stages'of'catabolism'11'Adenosine\5’\Triphosphate'(ATP)'Phosphate tail Adenine (base) Ribose (sugar) 2 α β γ 12'Phospho\'ester'bond'Phosphoric!Anhydride!Linkages''(Phosphoryl'Groups'with'High'Transfer'PotenBal)'in'Adenosine'NucleoBdes'13'Hydrolysis'of'Phosphoric'Acid'Anhydrides'is'Highly'Favorable'ΔG°’'='\30.5'kJ'mol\1'ATP'Orthophosphate'Pi'14'ADP'∆J'+'pyrophosphate!∆G°’='\45.6'kJ'mol\1'(PPi)'15'∆J'+'pyrophosphate!∆G°’='\33.6'kJ'mol\1'(PPi)'16'/!/!H!/!/!H!Hydrolysis'of'Pyrophosphate'Is'Also'Thermodynamically'Favorable'(Pi)'(Pi)'17'Three'ways'to'make'ATP'in'Eukaryotes'1. Substrate\level'phosphorylaBon:'Phosphate'is'transferred'to'ADP'in'a'coupled'reacBon'involving'from'a'molecule'with'an''high\phosphoryl'group'transfer'potenBal.'2. OxidaBve'phosphorylaBon'during'Cellular'respiraBon'by'ATP'phosphatase'3. CreaBne'kinase'Molecules'with'High\Phosphoryl'Group'Transfer'PotenBal'18'Coupled\ReacBon'For'ProducBon'of'ATP'''''''(Substrate\level'PhosphorylaBon)'PEP'+'H2O''''\\\>'''''pyruvate''+'Pi' ''''''''∆G'='\62.2'kJ/mol''''ADP'+'Pi'''''\\\>''''ATP'+'H2O ' ''''∆G'='+30.5'kJ/mol'PEP'+'ADP''''\\\>'''pyruvate'+'ATP''''''''''Overall'∆G'='\31.5'kJ/mol'19'ReacBons'(1)'and'(2)'are'coupled'(1)'(2)''∆G°’overall''='''∆G°’reacBon'1'+'∆G°’reacBon'2'If'the'net'∆G°’'value'(∆G°’overall)'is'sufficiently'negaBve,'forming'the'products'(eg.'pyruvate'and'ATP)'is'an'exergonic'process''(3)'Molecules'with'High\Phosphoryl'Group'Transfer'PotenBal'20'The'Large'NegaBve'Free'Energy'Change'of'ATP'Hydrolysis'Drives'many'Unfavorable'ReacBons'in'the'Cell'Example:''PhosphorylaBon'of'glucose'is'driven'by'hydrolysis'of'ATP'ATP'+'H2O'''''''''''''ADP'+'Pi'' ''''''''∆G°’reacBon'1'='\30.5'kJ/mol ''glucose'+'Pi''''''''''''G\6\P'''+'H2O ' '∆G°’reacBon'2'='+14'kJ/mol'glucose'+'ATP'''''''''''G\6\P'+'ADP'''' '∆G°’overall'='\16.5'kJ/mol'Coupled'reacBons'Molecules'with'High\Phosphoryl'Group'Transfer'PotenBal'22'23'Three'ways'to'make'ATP'in'Eukaryotes'1. Substrate\level'phosphorylaBon:'Phosphate'is'transferred'to'ADP'in'a'coupled'reacBon'involving'from'a'molecule'with'an''high\phosphoryl'group'transfer'potenBal.'2. OxidaBve'phosphorylaBon.'(ATP'phosphatase)'3. CreaBne'kinase'Sources'of'ATP'during'Excercise'Anaerobic'24'\IniBal'pool'[ATP]!1. Transient'forms'of'stored'energy'2. Thermodynamically'unstable(Favorable/spontaneous)''3. KineBcally'stable'(Does'not'hydrolyze'unpredictably)'''Two'important'properBes'of'high\energy'compounds'25'The'High'Phosphoryl\transfer'PotenBal'of'ATP'results'from'structural'differences'between'ATP'and'its'hydrolysis'Products'1. ElectrostaBc'Repulsion'2. Resonance'Stability'3. StabilizaBon'due'to'hydraBon'4. Increased'entropy'26'Hydrolysis'of'ATP'Causes'the'Relief'of'Charge'Repulsion'27'Resonance'Structures'of'Orthophosphate'(Pi)'28'There'are'fewer'resonance'structures'available'to'the'γ\phosphate'of'ATP'than'to'free'orthophosphate.'29'Hydrolysis'of'ATP'Increases'Entropy'O'\O' O'P'OR’'P'O'P'___ _ __\O'\O'\O'O' O'H+'OH'+'Pi'ADP'+'ATP'H2O'30'What'is'the'Daily'Human'Requirement'for'ATP?'• ResBng'human'consume'about'40'kg'of'ATP'in'24'hours,'and'up'to'0.5'kg'per'minute'of'strenuous'exercise.'• This'is'equivalent'to'60'kg'for'a'2\hr'run.'• The'typical'adult'human'body'contains'50\100'g'of'ATP/ADP'• Thus'each'ATP'molecule'must'be'recycled'nearly'1300'Bmes'per'day'• The'typical'ATP'molecule'is'consumed'within'1'min'of'its'producBon.'31'AcBvated'Carriers'during'Catabolism'• ADP/ATP'• NAD+/NADH'• FAD/FADH2'• FMN/FMNH2'32'hpp://classes.midlandstech.edu/carterp/courses/bio225/chap05/lecture3.htm'ReducBon'of'NAD+'33'reduced'oxidized'reduced' oxidized'H:\'''hydride''(2'e\'+'1'H+)'or'(H'+'1'e\)'Error'on'p.'257'of'text'(says'hydrite'H'+2'e\)'DehydrogenaBon'ReacBon'(1!H+!+!1!e/)!(1!H+!+!1!e/)!34'NicoBnamide'Adenine'DinucleoBde'(NAD+)'NAD+'Collects'Electrons'Released'in'Catabolism'H:\'reduced'oxidized'35'ReducBon'of'FAD/FMN'or!FMN!or!FMNH2!36'FAD,'Flavine'Adenine'DinucleoBde'Isoalloxazine'ring'D\ribitol'Riboflavin'a'water\'soluble'vitamin''Vit'B2'37'FMN, an electron carrier component of the ETC 'Isoalloxazine'ring'D\ribitol'38'AcBvated'Carriers'during'Anabolism'• ADP/ATP'• NADP+/NADPH'39'ReducBve'Biosynthesis'2'(NADPH'+'H+)'40'2'NADP+'+'The'structure'of'nicoBnamide'adenine'dinucleoBde'phosphate'(NADP+)'41'AcBvated'Carrier'of'Acyl'Group'Coenzyme'A'(CoA'or'CoASH)'Vit'B5'42'ADP'43'1. The'carriers'are'kineBcally'stable'in'the'absence'of'specific'catalysts.'2. The'metabolism'of'acBvated'groups'is'accomplished'with'a'small'number'of'carriers.'Two'characterisBcs'are'common'to'acBvated'carriers'44'(B9)'(B7)'(B5)'(B3)'45'RegulaBon'of'Glucose'Metabolism'Normal'blood'levels:'80'to'110'mg/dL'46'Diabetes'X!Type!1!Insulin/Dependent!Blood'sugar'remains'high'47'Diabetes'Type!1!Insulin/Dependent!X!X!Type!2!Insulin/Independent!Blood'sugar'remains'high'48'RegulaBon'of'Metabolic'Pathways'1. Amounts'of'enzyme'are'controlled'2. Accessibility'to'substrates'is'regulated'3. CatalyBc'acBvity'is'regulated'• PospranscripBonal'modificaBon'of'enzymes'•
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