Describe the function of glycolysis and identify its major products. Describe how the presence or absence of oxygen determines what happens to the pyruvate and the NADH that are produced in glycolysis. Determine the amount of ATP produced by the oxidation of glucose in the presence and absence of oxygen.

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In stage II of catabolism, the metabolic pathway known as glycolysis converts glucose into two molecules of pyruvate (a three-carbon compound with three carbon atoms) with the corresponding production of adenosine triphosphate (ATP). 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.


Steps in Glycolysis

The 10 reactions of glycolysis, summarized in Figures (PageIndex1) and (PageIndex2), can be divided into two phases. In the first 5 reactions—phase I—glucose is broken down into two molecules of glyceraldehyde 3-phosphate. In the last five reactions—phase II—each 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.


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Figure (PageIndex1): Phase 1 of Glycolysis
When glucose enters a cell, it is immediately phosphorylated to form glucose 6-phosphate, in the first reaction of phase I. The phosphate donor in this reaction is ATP, and the enzyme—which requires magnesium ions for its activity—is hexokinase. 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 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. In the next reaction, phosphoglucose isomerase catalyzes the isomerization of glucose 6-phosphate to fructose 6-phosphate. This reaction is important because it creates a primary alcohol, which can be readily phosphorylated. The subsequent phosphorylation of fructose 6-phosphate to form fructose 1,6-bisphosphate is catalyzed by phosphofructokinase, which requires magnesium ions for activity. ATP is again the phosphate donor.

When a molecule contains two phosphate groups on different carbon atoms, the convention is to use the prefix bis. When the two phosphate groups are bonded to each other on the same carbon atom (for example, adenosine diphosphate ), the prefix is di.


Fructose 1,6-bisphosphate is enzymatically cleaved by aldolase to form two triose phosphates: dihydroxyacetone phosphate and glyceraldehyde 3-phosphate. Isomerization of dihydroxyacetone phosphate into a second molecule of glyceraldehyde 3-phosphate is the final step in phase I. The enzyme catalyzing this reaction is triose phosphate isomerase.
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Figure (PageIndex2): Phase 2 of Glycolysis

In the initial step of phase II (Figure (PageIndex2)), glyceraldehyde 3-phosphate is both oxidized and phosphorylated in a reaction catalyzed by glyceraldehyde-3-phosphate dehydrogenase, an enzyme that requires nicotinamide adenine dinucleotide (NAD+) as the oxidizing agent and inorganic phosphate as the phosphate donor. In the reaction, NAD+ is reduced to reduced nicotinamide adenine dinucleotide (NADH), and 1,3-bisphosphoglycerate (BPG) is formed.


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.



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Because a person with diabetes is unable to use glucose properly, excessive quantities accumulate in the blood and the urine. Other characteristic symptoms are constant hunger, weight loss, extreme thirst, and frequent urination because the kidneys excrete large amounts of water in an attempt to remove excess sugar from the blood.

There are two types of diabetes. In immune-mediated diabetes, insufficient amounts of insulin are produced. This type of diabetes develops early in life and is also known as Type 1 diabetes, as well as insulin-dependent or juvenile-onset diabetes. Symptoms are rapidly reversed by the administration of insulin, and Type 1 diabetics can lead active lives provided they receive insulin as needed. Because insulin is a protein that is readily digested in the small intestine, it cannot be taken orally and must be injected at least once a day.

In Type 1 diabetes, insulin-producing cells of the pancreas are destroyed by the body’s immune system. Researchers are still trying to find out why. Meanwhile, they have developed a simple blood test capable of predicting who will develop Type 1 diabetes several years before the disease becomes apparent. The blood test reveals the presence of antibodies that destroy the body’s insulin-producing cells.

Type 2 diabetes, also known as noninsulin-dependent or adult-onset diabetes, is by far the more common, representing about 95% of diagnosed diabetic cases. (This translates to about 16 million Americans.) Type 2 diabetics usually produce sufficient amounts of insulin, but either the insulin-producing cells in the pancreas do not release enough of it, or it is not used properly because of defective insulin receptors or a lack of insulin receptors on the target cells. In many of these people, the disease can be controlled with a combination of diet and exercise alone. For some people who are overweight, losing weight is sufficient to bring their blood sugar level into the normal range, after which medication is not required if they exercise regularly and eat wisely.


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In glycolysis, how many molecules of pyruvate are produced from one molecule of glucose?



In anaerobic glycolysis, how many molecules of ATP are produced from one molecule of glucose?



There is a net production of two molecules of ATP.



Replace each question mark with the correct compound.

(mathrmfructose: 1,6 extrm-bisphosphate xrightarrowaldolase, ?, +, ?) (mathrm? + ADP xrightarrowpyruvate: kinase pyruvate + ATP) (mathrmdihydroxyacetone: phosphate xrightarrow? glyceraldehyde: 3 extrm-phosphate) (mathrmglucose + ATP xrightarrowhexokinase , ? + ADP)

Replace each question mark with the correct compound.

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(mathrmfructose: 6 extrm-phosphate + ATP xrightarrow? fructose: 1,6 extrm-bisphosphate + ADP) (mathrm? xrightarrowphosphoglucose: isomerase fructose: 6 extrm-phosphate) (mathrmglyceraldehyde: 3 extrm-phosphate + NAD^+ + P_i xrightarrow? 1,3 extrm-bisphosphoglycerate + NADH) (mathrm3 extrm-phosphoglycerate xrightarrowphosphoglyceromutase , ?)

From the reactions in Exercises 1 and 2, select the equation(s) by number and letter in which each type of reaction occurs.

isomerization oxidation

What coenzyme is needed as an oxidizing agent in glycolysis?


Calculate

the total number of molecules of ATP produced for each molecule of glucose converted to pyruvate in glycolysis. the number of molecules of ATP hydrolyzed in phase I of glycolysis. the net ATP production from glycolysis alone.
Calculate the number of moles of ATP produced by the aerobic oxidation of 1 mol of glucose in a liver cell. Of the total calculated in Exercise 9a, determine the number of moles of ATP produced in each process. glycolysis alone the citric acid cycle the electron transport chain and oxidative phosphorylation

NAD+