Lecture'17'*'Chapters'18+19'The'Tricarboxylic'Acid'Cycle'(TCA)'a.k.a.''Kreb’s'cycle'a.k.a.'Citric'Acid'Cycle'(CAC)'1'Outline'v 'Overview'of'the'process'of'complete'oxidaHon'of'glucose'(glycolysis'+'TCA'Cycle'+'OxidaHve'PhophorylaHon)''v 'Preparatory'step'for'TCA'Cycle'(Pyruvate'à'Acetyl'CoA)'v 'ReacHons'of'the'TCA'Cycle'(8)'v 'RegulaHon'of'the'TCA'Cycle'v 'TCA'Cycle'can'also'provide'precursors'for'biosynthesis'v 'AnapleroHc'reacHons'v 'The'glycoxylate'cycle'2'1x'2x'2x'2x'2x'2x'2x'2x'OxidaHve'phosphorylaHon'GTP/%NADH'3'NADH'1'FADH2'3'4'pyruvate'Pyruvate''+'CoA'+'NAD+''è Acetyl'CoA''+'CO2'+'NADH'+'H+'''The'Decisive'Step'*'The'Pyruvate'Dehydrogenase'Complex'5'PreparaHon'for'the'cycle'The'point'of'no'return'6'7'Pyruvate'Dehydrogenase'Complex'uses''three'CatalyHc'Coenzymes'(ProstheHc'groups)'FAD'Thiamine'pyrophosphate'(TPP)'Lipoic'acid'E1'E2'E3'Thiazole'ring'8'Lipoic'Acid'+'Lysine'='Lipoamide'9'Pyruvate'Dehydrogenase'Complex'uses''two'Stoichiometric'Coenzymes'NAD+'ATP'Pantothenic'acid'β*mercaptoethalamine'Coenzyme'A'(Bound'to'acetyl'group)'10'E2'E2'E1'E3'PDH'CatalyHc'and'Stoichiometric'Coenzymes'lipoamide'NAD+'CoA'11'The'synthesis'of'acetyl'CoA'from'pyruvate'consists'of'three'steps:'1''2''3'12'Step'1:'DecarboxylaHon'(E1)'13'Step'2.'OxidaHon'(E1):'Acetyl'group'is'oxidized'and'transferred'to'one'of'lipoamide'“S”.''The'other'“S”'of'lipoamide'is'reduced.'14'Step'3.'FormaHon'of'acetyl'CoA'(E2):'15'4.'ReoxidaHon'of'dihydrolipoamide'(E3)'16'5.'Transfer'of'electrons'to'NAD+'(E3)'17'h^p://iai.asm.org/content/28/3.to'Flexible'Linkages'Allows'Lipoamide'to'move'between'AcHve'Sites'18'High'blood'glucose'+''Low'energy'charge'Low'blood'glucose'+''High'energy'charge'RegulaHon'of'the'PDH'Complex'19'Pyruvate'dehydrogenase''''E1'''''E2''''E3'''NAD+'Acetyl'CoA'Pyruvate'NADH'Allosteric'RegulaHon'of'E2'and'E3'Acetyl'CoA'NADH'Substrates'ATP'Pyruvate'CoA'NAD+'Products'20'The'Covalent'RegulaHon'of'the'Pyruvate'Dehydrogenase'Component'(E1)'in'Higher'Eukaryotes'E1' E1'21'Pyruvate'dehydrogenase'''E1'''E2'''E3'acHve'Pyruvate'dehydrogenase'''E1'''E2'''E3'inacHve'P*'ATP'ADP'Pi'H2O'Pyruvate'dehydrogenase'kinase%Pyruvate'dehydrogenase'phosphatase%22'Pyruvate'dehydrogenase'''E1'''E2'''E3'acHve'Pyruvate'dehydrogenase'''E1'''E2'''E3'inacHve'P*'ATP'ADP'Pi'H2O'NAD+,'HS*CoA,'ADP,'Pyruvate'Pyruvate'dehydrogenase'kinase%Pyruvate'dehydrogenase'phosphatase%NADH,'Acetyl'CoA'High'energy'sHmulates'kinase'NAD+,'Ca2+'and'HS*CoA'Low'energy'sHmulates'phosphatase'éinsulin'(liver'and'adipose'éepinephrine'23'Advantages'of'MulHenzyme'Complexes'*
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