Download L10v02-glycolysis and TCA

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This is an overview of the central metabolic process which we will cover today –
glycolysis and the citric acid cycle.we will see today how this process makes a little bit of ATP, and a fair bit of NADH. We will see next Wednesday how that NADH gets converted into a lot more ATP.
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This is an overview of glycolysis in which one 6‐carbon molecule of glucose is converted into two 3‐carbon molecules of pyruvate. Pyruvate will cross the mitochondrial membranes for the start of the citric acid cycle.
As you can see here, two molecules of ATP are invested in steps one through three, while for molecules of ATP are produced in step seven and 10, for a net gain of two molecules of ATP. NADH is also produced in step six – this will be worth ATP molecules during the citric acid cycle. For this class, you will not need to memorize the structures ( but many will be on the MCATs).
No oxygen is required for these steps – hence this is anaerobic energy production.
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Step three is the “committed step”of glycolysis. Once you make the molecule fructose 1,6‐bisphosphate, you’re committed to going through with glycolysis. With fructose 6‐phosphate, the starting material, molecule can still be used for other purposes. Part of the reason this step “commits” the molecule to glycolysis is the investment of ATP energy – this could not be easily recouped.
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Details of the steps six and seven. For step six to occur, you need to have NAD+ available as a reactant ( more on this later). NADH and ATP are produced. ATP produced here is by a process referred to as “substrate level phosphorylation” because a specific enzyme transfers the phosphate group from 1,3‐
bisphosphoglycerate to a molecule of ADP. This is in contrast to the process we will see Wednesday in the mitochondria which is “oxidative phosphorylation”.
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A summary of the previous slide. As we will see, NADH carries high‐energy electrons. An aldehyde is oxidized to a carboxylic acid.
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The combined steps our net energy negative, despite the production of NADH and ATP.
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The sugars that we absorb from her bloodstream have undergone glycolysis in the cytosol producing pyruvate. Now pyruvate will cross the two mitochondrial membranes to the inner mitochondrial matrix, get converted to acetyl‐CoA, enter into the citric acid cycle. Fatty acids absorbed from the bloodstream get transferred directly to the mitochondria, and they will be broken down two carbons at a time into multiple copies of acetyl‐CoA.
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This is a schematic of the enzyme complex pyruvate dehydrogenase complex. One carbon of pyruvate will be released as carbon dioxide, leaving a two carbon unit that will be attached to CoEnzyme A, to form acetyl‐CoA. One amazing property of this enzyme complex is that the sub units rotate and transfer the individual reactants from one enzyme subunit directly to the next enzyme subunit, without releasing the molecule into the surrounding solvent where it could diffuse away. This greatly increases the rate and efficiency of the reaction.
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You won’t need to memorize this, but just so you see it, CoA is a sulfhydryl group attached by a linker to a molecule of ADP.
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Beta oxidation of fatty acids. Once inside the mitochondria, a fatty acid, which might have anywhere from 12 to 18 carbon molecules, are shortened by two carbons per cycle, always producing one molecule of acetyl‐CoA. The 12 carbon fatty acid could do this cycle six times. Each time the cycle occurs you produce a molecule of NADH and FADH2 ( very similar, but slightly less energetic) – these molecules will produce ATP later on. A molecule of acetyl‐CoA will enter into the citric acid cycle.
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This is just remind you that regardless of whether we’re talking about sugars or fats, at this point both molecules have been converted into acetyl‐CoA.
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This is the citric acid cycle. It is also called the “TCA cycle” or the “Krebs cycle”. TCA stands for “tri carboxylic acid.” Once again we will not be memorizing these structures in this class, but they are needed for MCATs. Entry into the citric acid cycle is a condensation of two carbon molecule of acetyl‐CoA would be for carbon molecule of oxaloacetate, producing the six carbon molecule citrate, aka citric acid. The rest of the cycle is involved with capturing energy in the form of high‐energy electrons (via NADH or FADH2), or GTP ( which can be used similarly to ATP In some cases). Carbon dioxide is released during this oxidation process. This is the carbon dioxide we exhale when we breathe. Note that we produce carbon dioxide before we utilize oxygen – it’s not the case that the oxygen we breathe gets converted directly into carbon dioxide .
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This is the structure of NADH, and its oxidized form NAD+. Electrons are added to NAD+ in the form of a hydride ion ( a proton with two electrons) Which is accommodated by the nicotinamide ring. Note the ADP portion of the molecule. (do not need to memorize)
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This is the structure of FAD, a flavin molecule attached to ADP. (do not need to memorize)
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This is an overview of the relevant metabolic processes going on in the mitochondria. We have produced NADH Via glycolysis and citric acid cycle, which will be used for oxidative phosphorylation for a very much larger payoff in ATP ( on Wednesday). Here for the first time, you can see why we breathe – at the end of oxidative phosphorylation we will dump the lower energy electrons onto an oxygen molecule, which will pick up protons from the solvent, to form a water molecule.
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As we mentioned, glycolysis does not use oxygen, it is an anaerobic process. It is the only way to make ATP without oxygen. The problem is we quickly run out of NAD+, and without it we can no longer make any ATP and the cell will grind to a halt. Normally we like to make NADH, because it is a valuable hi energy molecule, but it’s only valuable if we have oxygen around. So we have to get rid of the extra electrons. The way the cell accomplishes this is to add them to a molecule of pyruvate, producing lactic acid. This regenerates NAD+, and we can continue to make ATP. Lactic acid builds up is the molecule that causes muscle cramps during exercise when you do not have enough oxygen present in the tissue. Later on during recovery, lactic acid can be converted back to pyruvate, and we will recover NADH, which means we can get the much higher energy yield associated with oxidative phosphorylation.
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Other bacteria and yeast solves this problem by fermentation, dumping the electrons on acetaldehyde, producing ethanol.
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