BCHM 307 1nd Edition Lecture 33 Outline of Last Lecture I The Citric Acid Cycle A Other Names for the Cycle B Conditions to Function II An Overview of the Citric Acid Cyle III The Citric Acid Cycle Equation IV Where the TCA Cycle Occurs Outline of Current Lecture I Mitochondria II Pyruvate Dehydrogenase Complex III Steps of the Citric Acid Cycle Current Lecture This lecture continues on with the steps of the citric acid cycle The citric acid cycle occurs in the mitochondrion in eukaryotes specifically the mitochondrial matrix The mitochondria has an inner and out membrane The outer membrane is freely permeable to small molecules and ions The inner membrane contains the matrix and is impermeable to small ions In prokaryotes the citric acid cycle occurs in the cytoplasm The product of glycolysis that is need for the citric acid cycle is pyruvate Pyruvate has to get into the mitochondrial matrix somehow The pyruvate dehydrogenase complex bridges this gap This occurs in the mitochondria of eukaryotes and the cytosol of prokaryotes Pyruvate is able to cross 2 membranes through this reaction The pyruvate dehydrogenase complex is a quaternary structure consisting of a cluster of several enzymes Pyruvate is able to become Acetyl CoA through the complex Acetyl CoA is a better enzyme binding site The full equation for this reaction is given below CoA SH stands for Coenzyme A Coenzyme A contains a free thiol group which can form thioesters Pyruvate CoA SH NAD acetyl CoA CO2 NADH H Now that acetyl CoA has been formed the official citric acid cycle process can begin The steps of this process are listed below 1 Acetyl Co A has oxaloacetate and water added to it This forms citrate CoA SH and a hydrogen ion This reaction can only proceed forwards The oxaloacetate comes from the previous citric acid cycle and is the final end product formed Citrate synthase is the enzyme catalyzing this reaction 2 Citrate goes through a reversible reaction and forms isocitrate An enzyme bound intermediate is formed in between these steps which is cis Aconitate a water molecule This is an isomerization reaction catalyzed by aconitase 3 Isocitrate has NAD added to form alpha ketoglutarate carbon dioxide and NADH This is a redox reaction with NAD being reduced Isocitrate dehydrogenase catalyzes this reaction 4 Alpha ketoglutarate has CoASH and NAD added to it This forms succinyl CoA carbon dioxide NADH and a hydrogen ion This is a redox reaction catalyzed by alpha ketoglutarate dehydrogenase complex 5 Succinyl CoA had GDP and inorganic phosphate added to it This is a reversal reaction It forms succinate CoASH and GTP Succinate is perfectly symmetric molecule Succinyl CoA synthetase catalyzes this reaction 6 Succinate has FAD added to it This reversible reaction forms fumarate and FADH2 This is a redox reaction catalyzed by succinate dehydrogenase Succinate dehydrogenase is an insoluble enzyme associated with the inner mitochondrial membrane 7 Fumarate has water added to form L malate This is a reversible reaction This reaction is catalyzed by fumerase 8 Malate and NAD are combined to form oxaloacetate NADH and a hydrogen ion This is the final step of the citric acid cycle This is an example of a redox reaction and it is a reversible reaction catalyzed by malate dehydrogenase
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