Glycolysis - Biochemistry

Glucose-6-phosphate (G6P) is the first molecule of the pentose phosphate pathway where it is acted upon by glucose-6-phosphate dehydrogenase. G6P is the result of the hexokinase (first) reaction in glycolysis. What is key here is that the tissue in question is muscle. Because muscle cells lack the glucose-6-phosphatase necessary to produce free glucose from G6P, they cannot be said to perform gluconeogenesis. They do, however, perform glycogenesis through conversion of G6P to glucose-1-phosphate followed by conversion to uridine diphosphateglucose for addition to a growing molecule of glycogen.

Sucrose is the linking of glucose and fructose. Recall from the glycolytic pathway that fructose is further downstream than glucose, and therefore would allow for faster production of ATP.

First, we must realize that the first committed step is the first irreversible reaction of glycolysis that is unique to glycolysis (cannot lead to another process, such as the pentose phosphate pathway). This is the third step, in which fructose-6-phosphate is converted to fructose-1,6-bisphosphate (the correct answer).

Glucose is the beginning reactant of glycolysis, and pyruvate is the final product. Glucose-6-phosphate is the product of the first step of glycolysis overall, but not of the committed step.

Conversion of 1,3-bisphosphoglycerate to 3-phosphoglycerate is mediated by phosphoglycerate kinase. Conversion of phosphoenolpyruvate to pyruvate is mediated by pyruvate. In both these reactions adenosine diphosphate (ADP) is converted to ATP via substrate level phosphorylation. Conversion of 2-phosphoglycerate to phosphoenolpyruvate, mediated by enolase, does not produce ATP.

As glucose is introduced into the glycolytic pathway, it is first phosphorylated to create glucose-6-phosphate. That will then be converted to fructose-6-phosphate via phosphoglucose isomerase. That product will then be phosphorylated once more via phosphofructokinase-1 to create fructose-1,6-bisphosphate. Glucose-1,6-bisphosphate is never an observed intermediate in glycolysis.

In this question, we're shown a portion of glycolysis. We're asked to identify an intermediate in glycolysis based on the intermediate that comes before it and the one that comes after it.

To answer this, we'll need to know the pathway of glycolysis. The first intermediate shown here, glyceraldehyde-3-phosphate, is acted on by the enzyme glyceraldehyde-3-phosphate dehydrogenase. The product of this reaction is 1,3-bisphosphoglycerate, which is thus the correct answer. This intermediate is then acted on by the enzyme phosphoglycerate kinase to produce 3-phosphoglycerate.

Cellular respiration is a long process, and so it is easiest to break it into the following steps:

Step 1: Glycolysis

Step 2: Pyruvate decarboxylation

Step 3: Krebs cycle

Step 4: Oxidative phosphorylation

In the above steps, ATP is only produced by substrate-level phosphorylation in glycolysis and during the Krebs cycle.

In glycolysis, two molecules of pyruvate are produced for every molecule of glucose oxidized. During this process, two ATP molecules are consumed, but four are produced via substrate-level phosphorylation.

In the Krebs cycle, each pass of pyruvate through the cycle generates one molecule of GTP, which is subsequently used to generate a molecule of ATP via substrate-level phosphorylation. Thus, one molecule of ATP is produced via substrate-level phosphorylation per molecule of pyruvate oxidized. But remember that glycolysis produces two molecules of pyruvate for each molecule of glucose oxidized. Hence, the Krebs cycle will contribute a total of two molecules of ATP per glucose molecule oxidized.

Since we have a total of four moles ATP from glycolysis and two moles of ATP from the Krebs cycle (one per pyruvate), we have a cumulative production of six moles of ATP generated by substrate-level phosphorylation per mole of glucose oxidized.

The first and third steps of glycolysis involve energy consumption in the form of ATP. A phosphate group is added to glucose, and fructose-6-phosphate. In the seventh and tenth steps of glycolysis, ADP is phosphorylated at the level of the substrate into ATP. Since this is after glucose had been split into two three-carbon molecules, each molecule of glucose results in four ATP produced. However, since two were consumed early in glycolysis, the net ATP production is 2.

The first step of glycolysis is the addition of a phosphate group to glucose to form glucose-6-phosphate. The third step of glycolysis is the addition of another phosphate group to fructose-6-phosphate to form fructose-1,6-bisphosphate. The conversion of ATP to ADP is needed to supply the phosphate group in both of these reactions. These are the only two reactions in glycolysis where ATP is used to to add phosphate groups.

Glycolysis produces 4 ATP molecules. However, 2 ATP molecules are required to initiate glycolysis. Subtracting these two numbers gives the net ATP yield from glycolysis--2 ATP molecules.

Although glycolysis will ultimately produce 4 ATP, there is an initial requirement of 2 ATP for it to begin. The conversion of glucose to glucose-6-phosphate and the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate both require ATP.

The first and third steps of glycolysis are both energetically unfavorable. This means they will require an input of energy in order to continue forward. Per glucose molecule, 1 ATP is required for each of these steps. Therefore, a total of 2 ATP is needed during the energy investment phase of glycolysis.

Hexokinase and glucokinase are two enzymes that serve similar roles but have different characteristics. Hexokinase is found in all tissues, is inhibited by glucose 6 phosphate, and is not induced by insulin. It has a physiologic role of providing cells with a basal level of glucose 6 phosphate necessary for energy production.

In the glycolytic pathway, 2 molecules of ATP must be used. The purpose of these molecules is to phosphorylate 2 intermediates in the pathway:

1. Glucose must be phosphorylated to glucose-6-phosphate.

2. Fructose-6-phosphate must be phosphorylated to fructose-1,6-bisphosphate.

The first step in glycolysis is the conversion of glucose to glucose-6-phosphate through the consumption on one ATP molecule. Glucose is reacted upon by the enzyme hexokinase to carry out this step. Kinases are a group of enzymes that add phosphate groups by removing them from an ATP. All of these other enzymes catalyze subsequent reactions in glycolysis.

Dihydroxyacetone phosphate (DHAP) is converted to glyceradehyde-3-phosphate (G3P) by the enzyme triose phosphate isomerase. As the name suggests, this enzyme catalyzes the isomerization of a three-carbon sugar into another three-carbon sugar. Since the molecular formulas of DHAP and G3P are the same, we know that they are isomers of each other.

The balance between DHAP and G3P is extremely important in regulating overall cell metabolism. DHAP is a precursor to triglycerides, and is used in their synthesis, while G3P is an intermediate in glycolysis, an ATP-producing process. In order to favor the conversion of DHAP into G3P, and not the opposite, the cell must keep G3P levels low (Le Chatelier's Principle). Consider the following equilibrium: . This should make sense: if there is lots of ATP around in the cell, there is no need for glycolysis to proceed. Thus the equilibrium will be pushed to the left, increasing the concentration of DHAP in the cell. In humans, DHAP is converted into triglycerides, which get stored as fat. One way to shift this equilibrium to the right is to "create" an ATP need. This can be done by exercising. Exercise utilizes ATP and will thus pull the equilibrium to the right, removing DHAP (which was destined to be converted into fat) and facilitates its conversion into G3P to proceed with cellular respiration.

The tenth and final reaction of glycolysis involves the conversion of phosphoenolpyruvate (PEP) into pyruvate. This step is catalyzed by the enzyme pyruvate kinase. This kinase is going to remove a phosphate group from PEP and put it on ADP to yield ATP. Pyruvate, a three-carbon molecule, is the end product of glycolysis. It can be sent to the pyruvate dehydrogenase complex to be turned into acetyl-CoA, which enters the Krebs cycle. Alternatively, it can be reduced into lactate and/or ethanol (depending on the organism) to regenerate for glycolysis via anaerobic respiration.

Glyceraldehyde phosphate dehydrogenase (GAPDH) is used in the sixth reaction, where G3P is converted to 1,3-bisphosphoglycerate (1,3-BPG). A hydrogen is removed from G3P and added to , yielding NADH. Also, G3P has one phosphate group, while 1,3-BPG has two. The energy released as G3P is oxidized (causing subsequent reduction of ) is highly exergonic. This energy, sometimes referred to as the energy of oxidation, drives the addition of inorganic phosphate onto G3P, yielding the doubly-phosphorylated 1,3-BPG.

Theninth reaction involves the conversion of 2-phosphoglycerate into phosphoenolpyruvate. The enzyme enolase, which produces a double bond by removing the hydroxyl group on 2-phosphoglycerate catalyzes this reaction. Note that the resulting molecule is an enol (double bond -ene, and alcohol - ol).

Isomerases catalyze the isomerization, or rearrangement of atoms within a molecule, of its substrate. Isomerases are seen in glycolysis inn the second step where glucose-6-phosphate is converted into fructose-6-phosphate by phosphoglucose isomerase. Glucose-6-phosphate is rearranged into fructose-6-phosphate such that the molecular formula is unchanged. Another isomerase is triose phosphate isomerase. It catalyzes the isomerization of dihydroxyacetone phosphate to glyceraldehyde-3-phosphate.