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Home , Acetoacetic acid, Anabolism, Catabolism, Citric acid cycle, Fatty acid metabolism, Fatty acid synthesis

Metabolism: Citric Cycle & Related Pathways

Citric acid cycle a subset of the reactions of the cycle to pro- The primary catabolic pathway in the body duce a desired rather than to run the is the cycle because it is here that entire cycle (see HERE). oxidation to dioxide occurs for breakdown products of the ’s major build- Acetyl-CoA ing blocks - sugars, fatty , and amino The molecule “feeding” the is acids. The pathway is cyclic (Figure acetyl-CoA and it can be obtained from py- 6.63) and thus, doesn’t really have ruvate (from ), from a starting or ending point. All of YouTube Lectures β-oxidation, from ke- the reactions occur in mitochon- by Kevin tone bodies, and from amino HERE & HERE dria, though one is em- acid . bedded in the ’s inner from other pathways feeding into membrane. As needs change, cells may use the citric acid cycle for make the

541 citric acid cycle ‘cataplerotic’. It is worth cle intermediates are also important in amino noting that acetyl-CoA has very different acid metabolism (Figure 6.63), syn- fates, depending on the cell’s status/ thesis, electron shuttling, and shuttling of needs (see HERE). The description below de- acetyl-CoA across the mitochondrial inner scribes oxidation (catabolism) in citric acid membrane. The ability of the citric acid cy- cycle. cle to supply intermediates to pathways gives rise to the term ‘anaplerotic.’ It means ‘to Anabolically, acetyl-CoA is also very impor- fill up.’ Before discussing the citric acid cycle, tant for providing building blocks for synthe- it is important to first describe one important sis of fatty acids, bodies, amino enzyme complex that is a major source of acids and . Other citric acid cy- acetyl-CoA for the cycle.

Figure 6.63 - metabolism and the citric acid cycle. Amino acids boxed in yellow are made from the indicated intermediate. Amino acids in blue are made into the intermediate in catabolism. Image by Aleia Kim

542 Pyruvate The pyruvate enzyme is a complex of multiple copies of three subunits that catalyze the decarboxylation of pyru- vate to form acetyl-CoA. The reaction mechanism requires use of five coenzymes. is an enormous com- plex in mammals with a size five times greater than ribosomes.

Subunits

The three subunits are designated by E1, E2,

and E3. E2 is also referred to as dihydroli- Figure 6.64 - E1 Subunit of Pyruvate Dehydrogenase poamide acetyltransferase and E3 is more Wikipedia precisely called dihydrolipoyl dehydroge-

Figure 6.65 - Mechanism of action of and oxidation by pyruvate dehydrogenase.

543 nase. Confusion arises with the name for E1. tacks the electrophilic ketone carbon on the Some call it pyruvate dehydrogenase and oth- pyruvate, releasing and creat- ers give it the name pyruvate decarboxy- ing an enol that loses a proton on the carbon lase. We will use pyruvate decarboxylase to become a 1,3 dipole that includes the posi- solely to refer to E1 and pyruvate dehydroge- tively charged nitrogen of the . The nase only to refer to the complex of E1, E2, and reaction (step A in Figure 6.65) is a non-

E3. oxidative decarboxylation. Oxidation of the two carbon hydroxyethyl unit occurs in the The catalytic ac- transfer to the li- tions of pyruvate poamide. dehydrogenase can be broken Reductive down into three acetylation steps, each tak- Reductive acetyla- ing place on one tion occurs next of the subunits. (Step B) as the 2- The steps, se- carbon hy- quentially occur- droxyethyl unit ring on E1, E2, is transferred to and E3, are 1) de- lipoamide on E2. (Lipoamide is of pyruvate; 2) the name for a oxidation of the molecule of lip- decarboxylated Figure 6.66 - Oxidized and reduced structures of oic acid cova- product; and 3) lipoamide ( linked to ) lently attached to transfer of elec- a lysine side trons to ulti- chain in the E2 subunit). In in mately form NADH (Figure 6.65). the absence of , the hydroxyethyl group is not passed to lipoamide, but instead is re- leased as free acetaldehyde , which can ac- The catalytic process begins after binding of cept electrons from NADH (catalyzed by al- the pyruvate substrate with activation of the cohol dehydrogenase) and become etha- coenzyme nol in the process of . In the through formation of an ylide intermediate. presence of oxygen in almost all aerobic - The nucleophilic carbanion of the ylide at-

544 isms, the process continues with transfer of ess, electrons from FADH2 are transferred + the hydroxyethyl unit to E2 and con- to external NAD , forming NADH tinuation of the cycle below. YouTube Lectures (Step E) and completing the over- by Kevin all cycle. Then enzyme can then Oxidation step HERE & HERE begin another catalytic round by Transfer of the hydroxyethyl binding to a pyruvate. group from E1 to the lipoamide coenzyme in

E2 is an oxidation, with transfer of electrons Pyruvate dehydrogenase regulation from the hydroxyethyl group to lipoamide’s Pyruvate deyhdrogenase is regulated both disulfide (reducing it) and formation on the allosterically and by covalent modifica- lipoamide of an acetyl-thioester (oxidizing tion - / dephosphoryla- it).

The is then transferred from li- poamide to in E2 (Step C in Figure 6.65), forming acetyl- CoA, which is released and leaving reduced sulf- hydryls on the li- poamide. In order for the enzyme to return to its original state, the disul- fide bond on lipoamide must be re-formed. This occurs with transfer of elec- trons from reduced li- poamide to an FAD cova- lently bound to E3 (Step D). This reduces FAD to

FADH2. Figure 6.67 - Regulation scheme for pyruvate dehydroge- Formation of NADH nase (PD) Image by Aleia Kim In the last step in the proc-

545 tion by pyruvate dehydroge- nase (PDP).

PDK puts on any one of

three residues on the E1 subunit, which causes pyruvate ki- nase to not be able to perform its first step of catalysis - the decar- boxylation of pyruvate. PDP can remove those . PDK is allosterically activated in the mi- tochondrial matrix when NADH and acetyl-CoA concentra- tions rise. Figure 6.68 - Pyruvate dehydrogenase complex with three phosphorylation sites in red marked by Product inhibition arrows. Wikipedia Thus, the products of the pyruvate dehydrogenase reaction inhibit tion. Regulation of pyruvate dehydrogenase, the production of more products by favoring whether by allosteric or covalent mechanisms its phosphorylation by PDK. Pyruvate, a has the same strategy. Indicators of high en- substrate of pyruvate dehydrogenase, inhibits ergy shut down the enzyme, whereas indica- PDK, so increasing concentrations of sub- tors of low energy stimulate it. For allosteric strate activate pyruvate dehydrogenase by re- regulation, the high energy indicators affect- ducing its phosphorylation by PDK. As con- ing the enzyme are ATP, acetyl-CoA, centrations of NADH and acetyl-CoA fall, NADH, and fatty acids, which inhibit it. PDP associates with and re- AMP, Coenzyme A, NAD+, and calcium, on moves the phosphate on the serine on the E1 the other hand, stimulate it (Figure 6.67). subunit.

Covalent modification Low concentrations of NADH and acetyl-CoA Covalent modification regulation of pyru- are necessary for PDP to remain on the en- vate dehydrogenase is a bit more compli- zyme. When those concentrations rise, PDP cated. It occurs as a result of phosphoryla- dissociates and PDK gains access to the serine tion by pyruvate dehydrogenase kinase for phosphorylation. and calcium (PDK - Figure 6.67) or dephosphoryla- can also activate the PDP. This is very impor-

546 Figure 6.69 - The citric acid cycle image by Aleia Kim

547 tant in muscle , since calcium is a signal Acetyl-CoA + Oxaloacetate for muscular contraction, which requires en- ergy. Citrate + CoA-SH Insulin also also activates pyruvate kinase and the glycolysis pathway to use internal- In the next reaction, citrate is isomerized to ized . It should be noted that the isocitrate by action of the enzyme called aco- cAMP phosphorylation cascade from the β- nitase. has no effect on pyru- vate kinase, though the insulin cascade Citrate does, in fact, affect PDP and pyruvate kinase.

Citric acid cycle reactions Isocitrate Focusing on the pathway itself (Figure Isocitrate is a branch point in plants and bacte- 6.69), the usual point to start discussion is ad- ria for the glyoxylate cycle (see HERE). dition of acetyl-CoA to oxaloacetate (OAA) Oxidative decarboxylation of isocitrate by to form citrate.

Acetyl-CoA for the pathway can come from a vari- ety of sources. The reaction join- ing it to OAA is catalyzed by cit- rate and the ∆G°’ is fairly negative. This, in turn, helps to “pull” the malate de- hydrogenase reaction preced- ing it in the cy- Figure 6.70 - Succinyl-CoA synthetase mechanism cle.

548 produces the catalyzed by α-ketoglutarate dehydroge- first NADH and yields α-ketoglutarate. nase.

+ Isocitrate + NAD The enzyme α-ketoglutarate dehydrogenase is structurally very similar to pyruvate dehy- drogenase and employs the same five coen- α-ketoglutarate + NADH + CO2 zymes – NAD+, FAD, CoA-SH, thiamine This five carbon intermediate is a branch pyrophosphate, and lipoamide. point for synthesis of the amino acid gluta- mate. In addition, glutamate can also be Regeneration of oxaloacetate The remainder of the citric acid cycle involves made easily into this intermediate in the re- conversion of the four carbon succinyl-CoA verse reaction. Decarboxylation of α- into oxaloacetate. Succinyl-CoA is a branch ketoglutarate produces succinyl-CoA and is point for the synthesis of heme (see HERE). Succinyl-CoA is converted to succinate in a re- + α-ketoglutarate + NAD + CoA-SH action catalyzed by succinyl-CoA syn- thetase (named for the reverse reaction) and a GTP is produced, as well – the only sub- Succinyl-CoA + NADH + CO2 strate level phosphorylation in the cycle.

Succinyl-CoA + GDP + Pi

Succinate + GTP + CoA-SH

The energy for the synthesis of the GTP comes from of the high energy thioester bond between succinate and the CoA-SH. Evidence for the high energy of a thioester bond is also evident in the reaction, which is also very energetically favor-

Figure 6.71 - Succinate able. Succinate is also produced by metabo- dehydrogenase embedded in the lism of odd-chain fatty acids (see HERE). mitochondrial inner membrane (top) Wikipedia

549 Succinate Oxidation tion, fumarate, gains a across its trans Oxidation of succinate occurs in the next double bond in the next reaction, catalyzed by step, catalyzed by succinate dehydroge- to form malate. nase. Fumarate + H2O Succinate + FAD

L-Malate

Fumarate + FADH2 Fumarate is also a byproduct of This interesting enzyme both catalyzes this re- metabolism and of the cycle. Malate action and participates in the elec- is important also for transporting tron transport system, funnel- YouTube Lectures electrons across membranes in ing electrons from the FADH2 it by Kevin the malate-aspartate shuttle gains in the reaction to coen- HERE & HERE (see HERE) and in ferrying car- zyme Q. The product of the reac- bon dioxide from mesophyll cells

to bundle sheath cells in C4 plants (see HERE).

Rare oxidation Conversion of malate to ox- aloacetate by malate de- hydrogenase is a rare bio- logical oxidation that has a ∆G°’ with a positive value (29.7 kJ/mol). L-Malate + NAD+

Oxaloacetate + NADH

The reaction is ‘pulled’ by the energetically favorable Figure 6.72 - reaction conversion of oxaloacetate Image by Aleia Kim to citrate in the citrate

550 synthase reaction described above. Oxalo- indicators, such as ATP and NADH will tend intersects other important pathways, to inhibit the cycle and low energy indicators including amino acid metabolism (readily (NAD+, AMP, and ADP) will tend to activate converted to ), transamina- the cycle. Pyruvate dehydrogenase, which tion (nitrogen movement) and gluconeo- catalyzes formation of acetyl-CoA for entry genesis. into the cycle is allosterically inhibited by its product (acetyl-CoA), as well as by NADH It is worth noting that reversal of the citric and ATP. acid cycle theoretically provides a mecha- nism for assimilating CO2. In fact, this rever- Regulated sal has been noted in both anaerobic and mi- Regulated enzymes in the cycle include cit- croaerobic , where it is called the rate synthase (inhibited by NADH, ATP, Arnon-Buchanan cycle (Figure 6.73). and succinyl-CoA), isocitrate dehydroge- nase (inhibited by ATP, activated by ADP and Regulation of the citric acid cycle of the citric acid cy- cle is pretty straightfor- ward. The molecules involved are all substrates/products of the pathway or mole- cules involved in en- ergy transfer. Substrates/products that regulate or affect the pathway include acetyl-CoA and succinyl-CoA .

Inhibitors and activators Figure 6.73 - Arnon-Buchanon cycle. Alternative enzymes High energy molecular shown on right in lavender. Fd = ferredoxin Wikipedia

551 NAD+), and α-ketoglutarate dehydrogenase Cataplerotic molecules (inhibited by NADH and succinyl-CoA and The citric acid cycle’s primary cataplerotic activated by AMP). molecules include α- ketoglutarate, succinyl- Anaplerotic/ I love my citrate synthase It really is first rate CoA, and oxaloacetate. cataplerotic Adds O-A-A to Ac-Co-A of α- Producing one citrate pathway ketoglutarate and oxaloacetate The citric acid cycle is is picky produces the amino acids glu- Binds substrates specially an important catabolic Creating isocitrate tamate and aspartic acid, Which has no symmetry pathway oxidizing respectively. Oxaloacetate is acetyl-CoA into CO2 and Then CO2 gets lost from it important for the production Released in the next phase generating ATP, but it is The secret weapon - Isocitrate of glucose in gluconeogene- also an important source Dehydrogenase sis. of molecules needed by The alpha K–D-H is next It gets my admiration Glutamate plays a very impor- cells and a mechanism For clipping CO2 in one more tant role in the movement of for extracting energy Decarboxylation nitrogen through cells via glu- from amino acids in Succ-CoA synthetase steps up Reacting most absurd tamine and other molecules breakdown and It’s named for a catalysis and is also needed for other breakdown prod- That simply runs backward synthesis. Aspartate is a pre- ucts. This ability of the cit- Suc -CIN-ate de-hyd-ROG-en-ase cursor of other amino acids ric acid cycle to supply Pulls H from succinate Creating FADH2 and for production of py- molecules as needed and As well as fumarate rimidine . to absorb metabolic by- The fumarate gains water Succinyl-CoA is necessary products gives great flexi- O-H configured L The fumarase’s product? for the synthesis of por- bility to cells. When cit- Some malate for the cell phyrins, such as the heme ric acid cycle intermedi- With one last oxidation groups in , myo- ates are taken from the Malate de-hyd-ROG-en-ase Expels its two creations and . pathway to make other N-A-D-H / O-A-A molecules, the term used Kevin Ahern ˙ Citrate is an important to describe this is cata- source of acetyl-CoA for mak- plerotic, whereas when ing fatty acids. When the cit- molecules are added to the pathway, the proc- rate concentration is high (as when the citric ess is described as anaplerotic. acid cycle is moving slowly or is stopped), it gets shuttled across the mitochondrial

552 membrane into the and broken I’m thinking I could lose some weight down by the enzyme citrate lyase to oxalo- If I could make glyoxylate acetate and acetyl-CoA. The latter is a pre- Combined with acetyl-CoA cursor for in the cyto- Malate would then form OAA plasm. The excess OAA in turn Would give more glucose to be burned Anaplerotic molecules Converting to glucose, see Expends it glycolytically Anaplerotic molecules replenishing citric acid cycle intermediates include acetyl-CoA (made lyase and . The cycle oc- in many pathways, including fatty acid oxi- curs in specialized plant peroxisomes called dation, pyruvate decarboxylation, amino glyoxysomes. catalyzes the acid catabolism, and breakdown of ketone conversion of isocitrate into succinate and bodies), α-ketoglutarate (from amino acid metabolism), succinyl- CoA (from metabo- lism), fumarate (from the urea cy- cle and ), malate (carboxylation of PEP in plants), and oxaloacetate (many sources, in- cluding amino acid catabolism and action on py- ruvate in )

Glyoxylate cycle A pathway related to the citric acid cycle found only in plants and bacte- ria is the glyoxylate cycle (Figures 6.74 & 6.75). The glyoxylate cycle, which bypasses the decarboxyla- tion reactions while using most of the non-decarboxylation reactions of the citric acid cycle, does not operate in animals, because they lack two en- zymes necessary for it – isocitrate Figure 6.74 - Overview of the glyoxylate cycle Image by Aleia Kim

553 glyoxylate. Because of this, all six Succinate continues through the of the citric acid cycle sur- YouTube Lectures remaining reactions to produce vive each turn of the cycle and do by Kevin oxaloacetate. Glyoxylate com- HERE & HERE not end up as carbon dioxide. bines with another acetyl-CoA

Figure 6.75 - Reactions of the glyoxylate cycle Wikipedia

554 is particularly important for plant seed germi- nation (Figure 6.76), since the seedling is not exposed to sunlight. With the glyoxylate cycle, seeds can make glucose from stored .

Because animals do not run the glyoxylate cy- cle, they cannot produce glucose from acetyl- CoA in net amounts, but plants and bacteria can. As a result, plants and bacteria can turn acetyl-CoA from fat into glucose, while ani- Figure 6.76 - A gingko seed embryo mals can’t. Bypassing the oxidative decar- Wikipedia boxylations (and substrate level phos- (one acetyl-CoA was used to start the cycle) to phorylation) has energy costs, but, there are create malate (catalyzed by malate syn- also benefits. Each turn of the glyoxylate cy- thase). Malate can, in turn, be oxidized to ox- cle produces one FADH2 and one NADH in- aloacetate. stead of the three NADHs, one FADH2, and one GTP made in each turn of the citric acid It is at this point that the glyoxylate pathway’s cycle. contrast with the citric acid cycle is appar- ent. After one turn of the citric acid cycle, a needs single oxaloacetate is produced and it bal- that make cell walls, such as ances the single one used in the first reaction plants, fungi, and bacteria, need large quanti- of the cycle. Thus, in the citric acid cycle, ties of as they grow to sup- there is no net production of oxaloacetate in port the of the complex struc- each turn of the cycle. tural of the walls. These include cellulose, glucans, and chitin. Nota- Net oxaloacetate production bly, each of the organisms can operate the On the other hand, thanks to assimilation of glyoxylate cycle using acetyl-CoA from β- carbons from two acetyl-CoA molecules, each oxidation. turn of the glyoxylate cycle results in two ox- aloacetates being produced, after starting with Coordination of the glyoxylate one. The extra oxaloacetate of the glyoxylate cycle and the citric acid cycle cycle can be used to make other molecules, in- The citric acid cycle is a major catabolic cluding glucose in gluconeogenesis. This pathway producing a considerable amount of

555 Removal of the phos- phate from isocitrate dehydrogenase is catalyzed by an isocitrate dehydrognease- specific phos- phoprotein phos- phatase and re- stores activity to the enzyme.

When this happens, isocitrate oxidation resumes in the mito- chondrion along with Figure 6.77 - Acetyl-CoA metabolism Image by Aleia Kim the rest of the citric acid cycle reactions. energy for cells, whereas the glyoxylate cy- In bacteria, where the enzymes for both cycles cle’s main function is anabolic - to allow pro- are present together in the cytoplasm, accu- duction of glucose from fatty acids in mulation of citric acid cycle intermediates and plants and bacteria. The two pathways are glycolysis intermediates will tend to favor the physically separated from each other (glyoxy- citric acid cycle by activating the phosphatase, late cycle in glyoxysomes / citric acid cycle whereas high energy conditions will tend to in mitochondria), but nonetheless a coordi- favor the glyoxylate cycle by inhibiting it. nated regulation of them is important. Acetyl-CoA metabolism The enzyme that appears to provide controls Acetyl-CoA is one of the most “connected” for the cycle is isocitrate dehydrogenase. in , appearing in In plants and bacteria, the enzyme can be inac- fatty acid oxidation/synthesis, pyruvate tivated by phosphorylation by a kinase oxidation, the citric acid cycle, amino acid found only in those cells. Inactivation causes /catabolism, ketone body metabo- isocitrate to accumulate in the lism, / acid synthesis, and (by ex- and when this happens, it gets shunted to the tension from ) prosta- glyoxysomes, favoring the glyoxylate cycle. glandin synthesis . Most of these pathways

556 Figure 6.79 - Three - (top), (middle), and β- hydroxybutyrate (bottom)

by reversing the reaction of the pathway that makes them (Figure 6.78). Acetyl CoA, of course, can be used for ATP synthesis via the citric acid cycle. Peo- Figure 6.78 Ketone body metabolism Image by Pehr Jacobson ple who are very hypogly- cemic (including some will be dealt with separately. Here we will diabetics) will produce ketone bodies (Figure cover ketone body metabolism. 6.79) and these are often first detected by the smell of acetone on their breath. Ketone body metabolism Ketone bodies are molecules made when Overlapping pathways the levels of glucose fall very low. Ke- The pathways for ketone body synthesis tone bodies can be converted to acetyl-CoA and cholesterol biosynthesis (Figure 6.80

557 for fatty acid oxidation). In fact, the enzyme that catalyzes the joining is the same as the one that catalyzes its breakage in fatty acid oxidation – . Thus, these pathways start by revers- ing the last step of the last round of fatty acid oxidation.

HMG-CoA formation Both pathways also in- clude addition of two more carbons to acetoacetyl-CoA from a third acetyl-CoA to form hydroxy-methyl- glutaryl-CoA, or HMG- CoA, as it is more com- monly known. It is at this point that the two Figure 6.80 - Diverging biosynthetic pathways for ketone pathways diverge. HMG- bodies (left) and cholesterol biosynthesis (right) Image by Penelope Irving CoA is a branch point be- tween the two pathway and see HERE) overlap at the beginning. and can either go on to become choles- Each of these starts by combining terol or ketone bodies. In the latter two acetyl-CoAs together to make YouTube Lectures pathway, HMG-CoA is broken acetoacetyl-CoA. Not coinci- by Kevin down into acetyl-CoA and ace- HERE & HERE dentally, that is the next to last toacetate. product of β-oxidation of fatty acids with even numbers of carbons (see HERE Acetoacetate is itself a ketone body and can

558 be reduced to form another one, D-β- the supply of glucose is interrupted for any hydroxybutyrate (not actually a ketone, reason, the must supply an alternate en- though). Alternatively, acetoacetate can be ergy source. converted into acetone. This latter reaction can occur either spontaneously or via catalysis From fatty acid breakdown by acetoacetate decarboxylase. Acetone In contrast to glucose, ketone bodies can be can be converted into pyruvate and pyruvate made in animals from the breakdown of fat/ can be made into glucose. fatty acids. Most cells of the body can use ketone bodies as energy sources. D-β-hydroxybutyrate travels readily in the may arise from fasting, a very low carbohy- blood and crosses the blood-brain barrier. It drate diet or, in some cases, . can be oxidized back to acetoacetate, con- verted to acetoacetyl-CoA, and then broken down to two molecules of acetyl-CoA for oxi- The term acidosis refers to conditions in the dation in the citric acid cycle. body where the pH of arterial blood drops be-

Ketosis When a body is producing ketone bodies for its en- ergy, this state in the body is known as ketosis. Forma- tion of ketone bodies in the liver is critical. Normally glucose is the body’s pri- mary energy source. It comes from the diet, from the breakdown of storage car- bohydrates, such as glyco- gen, or from glucose synthe- sis (gluconeogenesis). Since the primary stores of are in muscles and liver and since gluconeo- genesis occurs only in liver, Figure 6.81 - Symptoms of acidosis , and gametes, when

559 low 7.35. It is the opposite of the condition of clude hypoventilation, pulmonary problems, alkalosis, where the pH of the arterial blood emphysema, asthma, and severe pneumonia. rises above 7.45. Normally, the pH of the blood stays in this narrow pH range. pH val- ues of the blood lower than 6.8 or higher than 7.8 can cause irreversible damage and may be fatal. Acidosis may have roots in metabo- lism (metabolic acidosis) or in respiration (respiratory acidosis).

There are several causes of acidosis. In meta- bolic acidosis, production of excess or failure of the kidneys to excrete acid can cause blood pH to drop. Lactic acid is pro- duced in the body when oxygen is limiting, so anything that interferes with oxygen delivery may create conditions favoring production of excess lactic acid. These may include restric- tions in the movement of blood to target tis- sues, resulting in hypoxia (low oxygen condi- tions) or decreases in blood volume. Issues with blood movement can result from heart problems, low blood pressure, or hemorrhag- ing.

Strenuous exercise can also result in produc- tion of lactic acid due to the inability of the blood supply to deliver oxygen as fast as tis- sues require it (hypovolemic ). At the end of the exercise, though, the oxygen supply via the blood system quickly catches up.

Respiratory acidosis arises from accumulation of carbon dioxide in the blood. Causes in-

560 Graphic images in this book were products of the work of several talented students. Links to their Web pages are below

Click HERE for Click HERE for Aleia Kim’s Pehr Jacobson’s Web Page Web Page

Click HERE for Click HERE for Penelope Irving’s Martha Baker’s Web Page Web Page

Problem set related to this section HERE Point by Point summary of this section HERE To get a certificate for mastering this section of the book, click HERE Kevin Ahern’s free iTunes U Courses - Basic / Med School / Advanced Biochemistry Free & Easy (our other book) HERE / Facebook Page Kevin and Indira’s Guide to Getting into Medical School - iTunes U Course / Book To see Kevin Ahern’s OSU ecampus courses - BB 350 / BB 450 / BB 451 To register for Kevin Ahern’s OSU ecampus courses - BB 350 / BB 450 / BB 451 Biochemistry Free For All Facebook Page (please like us) Kevin Ahern’s Web Page / Facebook Page / Taralyn Tan’s Web Page Kevin Ahern’s free downloads HERE OSU’s Biochemistry/Biophysics program HERE OSU’s College of Science HERE Oregon State University HERE Email Kevin Ahern / Indira Rajagopal / Taralyn Tan The Citric Acid Cycle To the tune of “When Irish Eyes Are Smiling” Metabolic Melodies Website HERE (This song uses only the chorus of the original song)

The citric acid cycle Is a source of energy It gets electrons moving While reducing NAD

It starts with citric acid Turning to aconitate Which becomes an isocitrate On the way to glutarate

The loss of one more carbon Gives succinyl-CoA And then When the CoA goes away

A further oxidation Gives one trans fumarate Which gains a water on the Next step to make malate

One simple oxidation Makes O-A-A you see Which combined with Ac-Co-A Returns us cyclically

Recording by David Simmons Lyrics by Kevin Ahern The Mellow Woes of Testing To the tune of "Yellow Rose of Texas" Metabolic Melodies Website HERE

The term is almost at an end Ten weeks since it began I had electron transport down I worried how my grade was cuz And all of complex vee I did not have a plan I gasped when I saw my exam It was a ninety three The first exam went not so well I got a sixty three So heading to the final stretch ‘Twas just about the average score I crammed my memory In biochemistry And came to class on sunny days For quizzing comedy I buckled down the second time Did not sow my wild oats I packed a card with info and I downloaded the videos My brain almost burned out And took a ton of notes ‘Twas much to my delight I Got the ‘A’ I’d dreamed about I learned about free energy And Delta Gee Naught Prime So here’s the moral of the song My score increased by seven points It doesn’t pay to stew A C-plus grade was mine If scores are not quite what you want And you don’t have a clue I sang the songs, I memorized I played the mp3s The answers get into your head I learned the citrate cycle When you know what to do And I counted ATPs Watch videos, read highlights and Re-

Recording by David Simmons Lyrics by Kevin Ahern

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