ch1131 chemical energy_glycolysis to oxidative p summary 2013

8/10/2019 CH1131 Chemical Energy_Glycolysis to Oxidative P Summary 2013

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GLYCOLYSIS - SUMMARY

What Is the Overall Pathway in Glycolysis?In glycolysis, one molecule of glucose gives rise, after a long series of reactions,

to two molecules of pyruvate. Along the way, two net molecules of ATP andNADH are produced.

How Is the 6-Carbon Glucose Converted to the 3-Carbon Glyceraldehyde-3Phosphate? In the first half of glycolysis, glucose is phosphorylated to glucose-6-phosphate, using an ATP in the process. Glucose-6-phosphate is isomerized tofructose-6-phosphate, which is then phosphorylated again to fructose-1,6-bisphosphate, utilizing another ATP. Fructose-1,6-bisphosphate is a keyintermediate, and the enzyme that catalyzes its formation, phosphofructokinase,is an important controlling factor in the pathway. Fructose 1,6-bisphosphate is

then split into two 3-carbon compounds, glyceraldehyde-3-phosphate anddihydroxyacetone phosphate, the latter of which is then also converted toglyceraldehyde-3-phosphate. The overall reaction in the first half of the pathwayis the conversion of one molecule of glucose into two molecules ofglyceraldehyde-3-phosphate at the expense of two molecules of ATP.

How Is Glyceraldehyde-3-Phosphate Converted to Pyruvate? Glyceraldehyde-3-phosphate is oxidized to 1,3-bisphosphoglycerate and NAD+ isreduced to NADH. The 1,3-bisphosphoglycerate is then converted to 3-phosphoglycerate and ATP is produced. 3-Phosphoglycerate is converted in two

steps to phosphoenol pyruvate, an important high-energy compound.Phosphoenol pyruvate is then converted to pyruvate and ATP is produced. Theoverall reaction of the second half of the pathway is that two molecules ofglyceraldehyde-3-phosphate are converted to two molecules of pyruvate and fourmolecules of ATP are produced.

How Is Pyruvate Metabolized Anaerobically?Several metabolic fates are possible for pyruvate. In aerobic metabolism,pyruvate loses carbon dioxide; the remaining two carbon atoms become linked tocoenzyme A as an acetyl group to form acetyl-CoA, which then enters the citric

acid cycle. There are two fates for pyruvate in anaerobic metabolism. Inorganisms capable of alcoholic fermentation, pyruvate loses carbon dioxide toproduce acetaldehyde, which, in turn, is reduced to produce ethanol. In otherorganisms, the common fate of pyruvate in anaerobic metabolism is reduction tolactate.



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How Much Energy Can Be Produced by Glycolysis?In each of two reactions in the pathway, one molecule of ATP is hydrolyzed foreach molecule of glucose metabolized. In each of two other reactions, twomolecules of ATP are produced by phosphorylation of ADP for each molecule ofglucose, giving a total of four ATP molecules produced. There is a net gain of two

ATP molecules for each molecule of glucose processed in glycolysis. Theanaerobic breakdown of glucose to lactate can be summarized as follows:

Glucose + 2 ADP + 2 Pi → 2 Lactate + 2 ATPThe overall process of glycolysis is exergonic.

GLYCOGEN METABOLISM - SUMMARY

How Is Glycogen Produced and Degraded?When an organism has an available supply of extra glucose, more than isimmediately needed as a source of energy extracted in glycolysis, it formsglycogen, a polymer of glucose. Glycogen synthase catalyzes the reactionbetween a glycogen molecule and UDP-glucose to add a glucose molecule to theglycogen via an α(1→4) linkage. Branching enzyme moves sections of a chain of

glucoses so that there are α(1→6) branch points. Glycogen can readily bebroken down to glucose in response to energy needs. Glycogen phosphorylaseuses phosphate to break an α(1→4) linkage, yielding glucose-1-phosphate and aglycogen molecule shorter by one glucose. Debranching enzyme aids in thedegradation of the molecule around the α(1→6) linkages. Control mechanismsensure that both formation and breakdown of glycogen are not activesimultaneously, a situation that would waste energy.

How Does Gluconeogenesis Produce Glucose from Pyruvate?The conversion of pyruvate (the product of glycolysis) to glucose takes place by

a process called gluconeogenesis. Gluconeogenesis is not the exact reversal ofglycolysis. There are three irreversible steps in glycolysis, and it is in these threereactions that gluconeogenesis differs from glycolysis. The net result ofgluconeogenesis is the reversal of these three glycolytic reactions, but thepathway is different, with different reactions and different enzymes.



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How Is Carbohydrate Metabolism Control led?In the same cell, glycolysis and gluconeogenesis are not highly activesimultaneously. When the cell needs ATP, glycolysis is more active; when thereis little need for ATP, gluconeogenesis is more active. Glycolysis andgluconeogenesis play roles in the Cori cycle. The division of labor between liver

and muscle allows glycolysis and gluconeogenesis to take place in differentorgans to serve the needs of an organism.Carbohydrate metabolism is controlled at several distinct points. Glycogensynthase and glycogen phosphorylase are reciprocally controlled byphosphorylation. Glycolysis and gluconeogenesis are controlled at several points,with phosphofructokinase and fructose bisphosphatase being the most important.Hexokinase and pyruvate kinase are also important control points.

Why Is Glucose Sometimes Diverted through the Pentose PhosphatePathway?

The pentose phosphate pathway is an alternative pathway for glucosemetabolism. In this pathway five-carbon sugars, including ribose, are producedfrom glucose. In the oxidative reactions of the pathway, NADPH is also produced.Control of the pathway allows the organism to adjust the relative levels ofproduction of five-carbon sugars and of NADPH according to its needs.

CITRIC ACID CYCLE - SUMMARY

What Role Does the Citric Acid Cycle Play in Metabolism?The citric acid cycle plays a central role in metabolism. It is the first part ofaerobic metabolism; it is also amphibolic (both catabolic and anabolic). Unlikeglycolysis, which takes place in the cytosol, the citric acid cycle occurs inmitochondria. Most of the enzymes of the citric acid cycle are in the mitochondrialmatrix. Succinate dehydrogenase, the sole exception, is localized in the innermitochondrial membrane.

What Is the Overall Pathway of the Citric Acid Cycle?Pyruvate produced by glycolysis is transformed by oxidative decarboxylation intoacetyl-CoA in the presence of coenzyme A. Acetyl-CoA then enters the citric acidcycle by reacting with oxaloacetate to produce citrate. The reactions of the citricacid cycle include two other oxidative decarboxylations, which transform the six-carbon compound citrate into the four-carbon compound succinate. The cycle iscompleted by regeneration of oxaloacetate from succinate in a multistep process



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that includes two other oxidation reactions. The overall reaction, starting withpyruvate, is

Pyruvate + 4 NAD+ + FAD + GDP + Pi + 2 H2O → 3 CO2 + 4 NADH +

FADH2 + GTP + 4 H+

NAD+ and FAD are the electron acceptors in the oxidation reactions. The cycle isstrongly exergonic.

How Is Pyruvate Converted to Acetyl-CoA? Pyruvate is produced by glycolysis in the cytosol of the cell. The citric acid cycletakes place in the matrix of the mitochondria, so the pyruvate must first passthrough a transporter into this organelle. There, pyruvate will find pyruvatedehydrogenase, a large, multisubunit protein made up of three enzymes involvedin the production of acetyl-CoA plus two enzyme activities involved in control of

the enzymes. The reaction requires several cofactors, including FAD, lipoic acid,and TPP.

What Are the Individual Reactions of the Citric Acid Cycle? Acetyl-CoA condenses with oxaloacetate to give citrate, a six-carbon compound.Citrate isomerizes to isocitrate, which then undergoes an oxidativedecarboxylation to α-ketoglutarate, a five-carbon compound. This thenundergoes another oxidative decarboxylation producing succinyl-CoA, a four-carbon compound. The two decarboxylation steps also produce NADH. Succinyl-CoA is converted to succinate with the concomitant production of GTP. Succinateis oxidized to fumarate, and FADH

2 is produced. Fumarate is converted to malate,

which is then oxidized to oxaloacetate while another NADH is produced.

What Are the Energetics of the Citric Acid Cycle, and How Is It Control led?The overall pathway has a ∆G°’ of –77.7 kJ mol –1. During the course of the cycle,starting from pyruvate, four NADH molecules and one FADH2 are produced.Between the GTP formed directly and the reoxidation of the reduced electroncarriers by the electron transport chain, the citric acid cycle produces 25 ATP.Control of the citric acid cycle is exercised at three points. There is also a controlpoint outside the cycle, the reaction in which pyruvate produces acetyl-CoA.Within the citric acid cycle, the three control points are the reactions catalyzed bycitrate synthase, isocitrate dehydrogenase, and the α-ketoglutaratedehydrogenase complex. In general, ATP and NADH are inhibitors, and ADP andNAD

+ are activators of the enzymes at the control points.



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What Role Does the Citric Acid Cycle Play in Catabolism? Like a giant trafficcircle of life, the citric acid cycle has many routes entering it. Many members ofthe three basic nutrient types, proteins, fats, and carbohydrates, are metabolizedto smaller molecules that can cross the mitochondrial membrane and enter thecitric acid cycle as one of the intermediate molecules. In this way, the cycle

allows us to get energy from the food we eat. Carbohydrates and many aminoacids can enter the cycle either as pyruvate or as acetyl-CoA. Lipids enter asacetyl-CoA. Because of the transamination reaction possible with glutamate andα-ketoglutarate, almost any amino acid can be transaminated to glutamate,producing α-ketoglutarate that can enter the cycle. Several other pathways leadto amino acids entering the pathway as succinate, fumarate, or malate.

What Role Does the Citric Acid Cycle Play in Anabolism? While the citric acid cycle takes place in mitochondria, many anabolic reactionstake place in the cytosol. Oxaloacetate, the starting material for gluconeogenesis,

is a component of the citric acid cycle. Malate, but not oxaloacetate, can betransported across the mitochondrial membrane. After malate from mitochondriais carried to the cytosol, it can be converted to oxaloacetate by malatedehydrogenase, an enzyme that requires NAD+. Malate, which crosses themitochondrial membrane, plays a role in lipid anabolism, in a reaction in whichmalate is oxidatively decarboxylated to pyruvate by an enzyme that requiresNADP+, producing NADPH. This reaction is an important source of NADPH forlipid anabolism, with the pentose phosphate pathway the only other source. Inaddition, most of the intermediates have anabolic pathways leading to aminoacids and fatty acids, as well as some that lead to porphyrins or pyrimidines.

ELECTRON TRANSPORT AND OXIDATIVE PHOSPHORYLATION- SUMMARY

What Role Does Electron Transport Play in Metabolism? In the final stages of aerobic metabolism, electrons are transferred from NADH tooxygen (the ultimate electron acceptor) in a series of oxidation–reductionreactions known as the electron transport chain. This series of events isdependent upon the presence of oxygen in the final step. This pathway allows forthe reoxidation of the reduced electron carriers produced in glycolysis, the citricacid cycle, and several other catabolic pathways, and is the true source of the

ATPs produced by catabolism.

What Are the Reduction Potentials for the Electron Transport Chain?



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The overall reaction of the electron transport chain shows a very large, negative ∆G°’ due to the large differences in reduction potentials between the reactionsinvolving NADH and those involving oxygen. If NADH were to reduce oxygendirectly, the ∆E°’ would be more than 1 V. In reality, there are many redoxreactions in between, and the correct order of events in the electron transport

chain was predicted by comparing the reduction potentials of the individualreactions long before the order was established experimentally.

How Are the Electron Transport Complexes Organized? Four separate respiratory complexes can be isolated from the inner mitochondrialmembrane. Each of the respiratory complexes can carry out the reactions of aportion of the electron transport chain. In addition to the respiratory complexes,two electron carriers, coenzyme Q and cytochrome c, are not bound to thecomplexes but are free to move within and along the membrane, respectively.Complex I accomplishes the reoxidation of NADH and sends electrons to

Coenzyme Q. Complex II reoxidizes FADH2 and also sends electrons to CoQ.Complex III involves the Q cycle and shuttles electrons to cytochrome c.

Complex IV takes the electrons from cytochrome c and passes them to oxygen inthe final step of electron transport.

What Is the Connection between Electron Transport and Phosphorylation? During the process of electron transport, several reactions occur in whichreduced carriers that have both electrons and protons to donate are linked tocarriers that can only accept electrons. At these points, hydrogen ions arereleased to the other side of the inner mitochondrial membrane, causing theformation of a pH gradient. The energy inherent in the charge and chemicalseparation of the hydrogen ions is used to phosphorylate ADP to ATP when thehydrogen ions pass back into the mitochondria through ATP synthase.

What Is the Mechanism of Coupling in Oxidative Phosphorylation? A complex protein oligomer is the coupling factor that links oxidation andphosphorylation. The complete protein spans the inner mitochondrial membraneand projects into the matrix as well. The portion of the protein that spans themembrane is called F0; it consists of three different kinds of polypeptide chains (a,b, and c). The portion that projects into the matrix is called F1; it consists of fivedifferent kinds of polypeptide chains (α, β, γ, δ, and Є, in the ratio α3 β 3 γ δ Є).The F1 sphere is the site of ATP synthesis. The whole protein complex is called

ATP synthase. It is also known as mitochondrial ATPase. Two mechanisms, thechemiosmotic mechanism and the conformational coupling mechanism, havebeen proposed to explain the coupling. Chemiosmotic coupling is the mechanismmost widely used to explain the manner in which electron transport and oxidativephosphorylation are coupled to one another. In this mechanism, the protongradient is directly linked to the phosphorylation process. The way in which the



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proton gradient leads to the production of ATP depends on ion channels throughthe inner mitochondrial membrane; these channels are a feature of the structureof ATP synthase. Protons flow back into the matrix through proton channels inthe F0 part of the ATP synthase. The flow of protons is accompanied by formationof ATP, which occurs in the F1 unit. In the conformational coupling mechanism,

the proton gradient is indirectly related to ATP production. It appears from recentevidence that the effect of the proton gradient is not the formation of ATP but therelease of tightly bound ATP from the synthase as a result of the conformationalchange.

What Are Shuttle Mechanisms?Shuttle mechanisms allow the transfer the electrons, but not the NADH,produced in cytosolic reactions into the mitochondrion.

ch1131 chemical energy_glycolysis to oxidative p summary 2013

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