{"id":2229,"date":"2018-03-21T20:41:20","date_gmt":"2018-03-21T20:41:20","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/suny-orgbiochemistry\/?post_type=chapter&p=2229"},"modified":"2018-12-11T13:18:43","modified_gmt":"2018-12-11T13:18:43","slug":"20-5-stage-ii-of-carbohydrate-catabolism","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-monroecc-orgbiochemistry\/chapter\/20-5-stage-ii-of-carbohydrate-catabolism\/","title":{"raw":"20.5 Stage II of Carbohydrate Catabolism","rendered":"20.5 Stage II of Carbohydrate Catabolism"},"content":{"raw":"
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Learning Objectives<\/h3>\r\n
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  1. Describe the function of glycolysis and identify its major products.<\/li>\r\n \t
  2. Describe how the presence or absence of oxygen determines what happens to the pyruvate and the NADH that are produced in glycolysis.<\/li>\r\n \t
  3. Determine the amount of ATP produced by the oxidation of glucose in the presence and absence of oxygen.<\/li>\r\n<\/ol>\r\n<\/div>\r\n<\/div>\r\n

    In stage II of catabolism of carbohydrates, glucose (six carbon) is broken down to two molecules of pyruvate (three carbons each) through the metabolic pathway known as glycolysis<\/span><\/strong>, <\/span>with the corresponding production of ATP.<\/span><\/span> The individual reactions in glycolysis were determined during the first part of the 20th century. It was the first metabolic pathway to be elucidated, in part because the participating enzymes are found in soluble form in the cell and are readily isolated and purified. The pathway is structured so that the product of one enzyme-catalyzed reaction becomes the substrate of the next. The transfer of intermediates from one enzyme to the next occurs by diffusion.<\/span><\/p>\r\n\r\n<\/div>\r\n

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    Steps in Glycolysis<\/h2>\r\n

    The 10 reactions of glycolysis, summarized in Figure 20.16 \"Glycolysis\"<\/a>, can be divided into two phases. In the first 5 reactions\u2014phase I\u2014glucose is broken down into two molecules of glyceraldehyde 3-phosphate. In the last five reactions\u2014phase II\u2014each glyceraldehyde 3-phosphate is converted into pyruvate, and ATP is generated. Notice that all the intermediates in glycolysis are phosphorylated and contain either six or three carbon atoms.<\/p>\r\n\r\n[caption id=\"attachment_3648\" align=\"alignnone\" width=\"771\"]\"\" Figure 20.16\u00a0 Glycolysis.Attribution: WYassineMrabetTalk\u2709 This W3C-unspecified vector image was created with Inkscape. [CC BY-SA 3.0 (https:\/\/creativecommons.org\/licenses\/by-sa\/3.0) or GFDL (http:\/\/www.gnu.org\/copyleft\/fdl.html)], from Wikimedia Commons[\/caption]\r\n

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    When glucose<\/strong> enters a cell, it is immediately phosphorylated to form glucose 6-phosphate<\/strong>, in the first reaction of phase I. The phosphate donor in this reaction is ATP, and the enzyme\u2014which requires magnesium ions for its activity\u2014is hexokinase<\/em>. In this reaction, ATP is being used rather than being synthesized. The presence of such a reaction in a catabolic pathway that is supposed to generate<\/em> energy may surprise you. However, in addition to activating the glucose molecule, this initial reaction is essentially irreversible, an added benefit that keeps the overall process moving in the right direction. Furthermore, the addition of the negatively charged phosphate group prevents the intermediates formed in glycolysis from diffusing through the cell membrane, as neutral molecules such as glucose can do.<\/p>\r\n

    In the next reaction, phosphoglucose isomerase<\/em> catalyzes the isomerization of glucose 6-phosphate<\/strong> to fructose 6-phosphate<\/strong>. This reaction is important because it creates a primary alcohol, which can be readily phosphorylated.<\/p>\r\n

    The subsequent phosphorylation of fructose 6-phosphate<\/strong> to form fructose 1,6-bisphosphate<\/strong> is catalyzed by phosphofructokinase<\/em>, which requires magnesium ions for activity. ATP is again the phosphate donor.<\/p>\r\n\r\n

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    Note<\/h3>\r\n

    When a molecule contains two phosphate groups on different carbon atoms, the convention is to use the prefix bis<\/em>. When the two phosphate groups are bonded to each other on the same carbon atom (for example, adenosine diphosphate [ADP]), the prefix is di<\/em>.<\/p>\r\n\r\n<\/div>\r\n<\/div>\r\n

    Fructose 1,6-bisphosphate<\/strong> is enzymatically cleaved by aldolase<\/em> to form two triose phosphates: dihydroxyacetone phosphate<\/strong> and glyceraldehyde 3-phosphate<\/strong>.<\/p>\r\n

    Isomerization of dihydroxyacetone phosphate<\/strong> into a second molecule of glyceraldehyde 3-phosphate<\/strong> is the final step in phase I. The enzyme catalyzing this reaction is triose phosphate isomerase<\/em>.<\/p>\r\n

    Comment<\/strong>: In steps 4 and 5, aldolase and triose phosphate isomerase effectively convert one molecule of fructose 1,6-bisphosphate into two<\/em> molecules of glyceraldehyde 3-phosphate. Thus, phase I of glycolysis requires energy in the form of two molecules of ATP and releases none of the energy stored in glucose.<\/p>\r\n

    In the initial step of phase II, glyceraldehyde 3-phosphate<\/strong> is both oxidized and phosphorylated in a reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase<\/em>, an enzyme that requires nicotinamide adenine dinucleotide (NAD+<\/sup>) as the oxidizing agent and inorganic phosphate as the phosphate donor. In the reaction, NAD+<\/sup> is reduced to reduced nicotinamide adenine dinucleotide (NADH + H+<\/sup>), and 1,3-bisphosphoglycerate (BPG)<\/strong> is formed.<\/p>\r\n

    BPG<\/strong> has a high-energy phosphate bond (see Table 20.1 \"Energy Released by Hydrolysis of Some Phosphate Compounds\"<\/a>) joining a phosphate group to C1. This phosphate group is now transferred directly to a molecule of ADP, thus forming ATP<\/strong> and 3-phosphoglycerate<\/strong>. The enzyme that catalyzes the reaction is phosphoglycerate kinase<\/em>, which, like all other kinases, requires magnesium ions to function. This is the first reaction to produce ATP in the pathway. Because the ATP is formed by a direct transfer of a phosphate group from a metabolite to ADP\u2014that is, from one substrate to another\u2014the process is referred to as substrate-level phosphorylation,<\/span><\/span> to distinguish it from the oxidative phosphorylation<\/em> discussed in Section 20.4 \"Stage III of Catabolism\"<\/a>.<\/p>\r\n

    In the next reaction, the phosphate group on 3-phosphoglycerate<\/strong> is transferred from the OH group of C3 to the OH group of C2, forming 2-phosphoglycerate<\/strong> in a reaction catalyzed by phosphoglyceromutase<\/em>.<\/p>\r\n

    A dehydration reaction, catalyzed by enolase<\/em>, transforms\u00a02-phosphoglycerate<\/strong> into phosphoenolpyruvate (PEP)<\/strong>, another compound possessing a high-energy phosphate group.<\/p>\r\n

    The final step is irreversible and is the second reaction in which substrate-level phosphorylation occurs. The phosphate group of PEP<\/strong> is transferred to ADP, with one molecule of ATP<\/strong> being produced per molecule of PEP. With the removal of the phosphate group, PEP<\/strong> becomes pyruvate.\u00a0 <\/strong>The reaction is catalyzed by pyruvate kinase<\/em>, which requires both magnesium and potassium ions to be active.<\/p>\r\n

    Comment<\/strong>: In phase II, two molecules of glyceraldehyde 3-phosphate are converted to two molecules of pyruvate, along with the production of four molecules of ATP and two molecules of NADH.<\/p>\r\n\r\n

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    To Your Health: Diabetes<\/h3>\r\n

    Most of the chapter-opening essays in Chapter 16 \"Carbohydrates\"<\/a> through Chapter 20 \"Energy Metabolism\"<\/a> have touched on different aspects of diabetes and the role of insulin in its causation and treatment. Although medical science has made significant progress against this disease, it continues to be a major health threat. Some of the serious complications of diabetes are as follows:<\/p>\r\n\r\n