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50 Cards in this Set
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- Back
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What is fluoroacetate and where is it found?
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It is found in poisonous plants and it is the active ingredient in compound 1080, which is used by ranchers to kill coyotes and foxes
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What do cells do with fluoroacetate?
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They convert it to fluorocitrate, which is a potent inhibitor of the citrate cycle enzyme mitochondrial aconitase
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What is the fuel for this metabolic engine?
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Acetyl-CoA
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What is the exhaust?
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Two molecules of CO2
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What is the energy output?
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8 electrons (redox energy) and one GTP that is converted to ATP (phosphoryl transfer energy)
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How many ATP are generated from one NADH?
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~ 2.5 ATP/NADH
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How many ATP are generated from one FADH2?
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~ 1.5 ATP/NADH
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Each turn of the cycle produces how many ATP for every acetyl-CoA?
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~ 10 ATP
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What is this metabolic engine dependent on?
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It is dependent on a constant supply of O2, just like a combustion engine
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Why do we refer to this as the citrate cycle?
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It's called the citrate cycle because citrate is the first product of the pathway and the unprotonated form of citric acid is the predominant species at this physiological pH
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What does the citrate cycle accomplish for the cell?
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It transfers 8 electrons from acetyl-CoA to the coenzymes NAD+ and FAD to form 3 NADH and 1 FADH2, which are then re-oxidized by the electron transport chain to produce ATP by the process of oxidative phosphorylation. It generates 2 CO2 as waste products and uses substrate level phosphorylation to generate 1 GTP which is converted to ATP by nucleoside disphosphate kinase. It supplies metabolic intermediates for amino acid and porphyrin biosynthesis
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What is the overall net reaction of the citrate cycle?
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Acetyl-CoA + 3 NAD+ + FAD + GDP + Pi + 2 H2O --> CoA + 2 CO2 + 3 NADH + 3 H+ + FADH2 + GTP
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Is this reaction favorable?
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Yes, very.
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What are the key enzymes of the citrate acid cycle?
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Pyruvate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and alpha-keyoglutarate dehydrogenase
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What does pyruvate dehydrogenase do?
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It is critical to flux of acetyl-CoA through the cycle
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How many coenzymes does pyruvate dehydrogenase require?
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It requires 5 coenzyme
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What is pyruvate dehydrogenase activated by?
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It is activated by NAD+, CoA, and Ca2+ (in muscle cells)
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What is pyruvate dehydrogenase inhibited by?
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It is inhibited by acetyl-CoA, ATP, and NADH
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What does citrate synthase do?
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It catalyzes the first reaction in the pathway
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What is citrate synthase inhibited by?
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It is inhibited by citrate, succinyl-CoA, NADH, and ATP
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How in inhibition of citrate synthase reversed?
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It is reversed by ADP
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What does isocitrate dehydrogenase do?
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It catalyzes the oxidative decarboxylation of isocitrate
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How does it accomplish this?
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It transfers two electrons to NAD+ to form NADH, and in the process, releases CO2
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What is isocitrate dehydrogenase activated by?
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It is activated by ADP and Ca2+
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What is isocitrate dehydrogenase inhibited by?
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It is inhibited by NADH and ATP
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What does alpha-ketoglutarate dehydrogenase do?
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It catalyzes an oxidative decarboxylation reaction that produces CO2, NADH, and succinyl-CoA
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What is it activated by?
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It is activated by Ca2+ and AMP
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What is it inhibited by?
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It is inhibited by NADH, succinyl-CoA, and ATP
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What are examples of the citrate cycle in real life?
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Citrate is produced commercially by fermentation methods
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What is Citrate?
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It is a flavor enhancer and food preservative
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What happens in the first four reactions of the citrate cycle?
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The two carbon acetate group of acetyl-CoA is linked to the four carbon oxaloacetate substrate to form a six carbon citrate molecule
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What happens to the citrate then?
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It is transformed into isocitrate
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What does becoming isocitrate allow?
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It allows two decarboxylation reactions to take place, yielding two NADH and the high energy four carbon cycle intermediate succinyl-CoA.
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What happens in the second half of the cycle?
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oxaloacetate is regenerated from succinyl-CoA by four successive reactions that lead to the formation of one GTP (ATP), one FADH2, and one NADH
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What happens in reaction 1 of the citrate cycle?
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A condensation occurs of oxaloacetate and acetly-CoA by citrate synthase to form citrate
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What occurs in reaction 2 of the citrate cycle?
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Isomerization of citrate by aconitase occurs to form isocitrate
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What occurs in reaction 3 of the citrate cycle?
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Oxidative decarboxylation of isocitrate by isocitrate dehydrogenase occurs to form alpha-ketoglutarate, CO2, and NADH
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What occurs in reaction 4 of the citrate cycle?
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Oxidative decarboxylation of alpha-ketoglutarate by alpha-ketoglutarate dehydrogenase occurs to form succinyl-CoA, CO2, and NADH
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What occurs in reaction 5 of the citrate cycle?
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A conversion occurs of succinyl-CoA to succinate by succinyl-CoA synthetase in a subtrate level phosphorylation reaction that generates GTP
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What does the enzyme nucleoside disphosphate kinase do?
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It interconverts GTP and ATP by a readily reversible phosphoryl transfer reaction
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What occurs in reaction 6 of the citrate cycle?
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Oxidation of succinate by succinate dehydrogenase occurs to form fumarate
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What occurs during reaction 7 of the citrate cycle?
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Hydration of fumarate by fumarase occurs to form malate
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What occurs during reaction 8 of the citrate cycle?
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Oxidation of malate by malate dehydrogenase occurs ot form oxaloaceate
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By combining the glycolytic pathway, the pyruvate dehydrogenase reaction, and the citrate cycle into one complete circuit, we obtain what net reaction?
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Glucose + 2 H2O + 10 NAD+ + 2 FAD + 4 ADP + 4 Pi --> 6 CO2 + 10 NADH + 6 H+ + 2 FADH2 + 4 ATP
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How is the citrate cycle significantly different than glycolysis pertaining to end products?
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The end product of the citrate cycle pathway, oxaloacetate, is the substrate for the first reaction
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What does this infer about flux through the pathway?
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It is continually monitored by resetting the level of available substrate after each turn of the cycle
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In addition to substrate available, what are the two other regulatory mechanisms at play in the citrate cycle?
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Product inhibition and feedback control of key enzymes
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What role does NADH and FADH2 have in connecting the citrate cycle to ATP synthesis?
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NADH and FADH2 function as carrier molecules that transport electron pairs from redox reaction in the citrate cycle to the electron transport system where they are reoxidized to provide redox energy that can be harnessed for ATP synthesis
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Why is the citrate cycle considered the hub of metabolism?
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It is considered the hub of metabolism because it provides the crucial link between oxidation of acetyl-CoA and ATP synthesis, and in addition, provides metabolic precursors for the biosynthesis of amino acids, fatty acids, cholesterol, heme, and glucose
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What is the primary function of the citrate cycle in terms of energy conversion reactions?
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It oxidizes acetyl-CoA, and in the process, transfers four pairs of electrons from citrate cycle intermediates to 3 moles of NADH and 1 mole of FADH2 during each turn of the cycle
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