Catabolism of Carbohydrates: Glycolysis: Videos & Practice Problems

Glycolysis is a crucial metabolic pathway consisting of a series of 10 biochemical reactions that convert glucose into pyruvate, while also generating energy-rich molecules. The process can be divided into two main phases: the first half, comprising reactions 1 to 5, involves the breakdown of one glucose molecule into two molecules of Glyceraldehyde 3-Phosphate (G3P). This initial phase is essential for preparing the substrate for energy extraction.

In the second half, reactions 6 to 10, the G3P molecules are further processed to produce pyruvate. During this phase, high-energy molecules such as ATP (adenosine triphosphate) and NADH (nicotinamide adenine dinucleotide) are generated. ATP serves as the primary energy currency of the cell, while NADH plays a critical role in cellular respiration by carrying electrons to the electron transport chain.

Overall, glycolysis is a vital pathway for energy production, especially in anaerobic conditions, and serves as a foundational process in cellular metabolism.

In the process of phosphorylation, a significant reaction occurs where the hydroxyl group on Carbon 6 of alpha glucose attacks the gamma phosphorus of ATP. This interaction initiates a series of steps leading to the formation of alpha glucose 6-phosphate. Initially, a basic residue deprotonates the hydroxyl group, allowing a lone pair of electrons to attack the phosphorus atom. This results in the cleavage of the bond between the phosphorus and an oxygen atom, effectively releasing an oxygen atom and forming a new bond between the phosphate group and the oxygen of the alpha glucose.

This reaction can be classified as an S_N2 reaction, characterized by a single-step mechanism where the nucleophile (the hydroxyl group) displaces the leaving group (the oxygen atom). The outcome of this phosphorylation is the conversion of alpha glucose into alpha glucose 6-phosphate, while simultaneously transforming ATP into ADP by losing a phosphate group. This reaction is a crucial step in glycolysis, highlighting the importance of ATP as an energy currency in cellular metabolism.

In the isomerization reaction of glycolysis, Alpha Glucose 6 Phosphate is converted into Alpha Fructose 6 Phosphate through a series of steps involving an enediol intermediate. Initially, the cyclic form of Alpha Glucose 6 Phosphate can also exist in a linear form as Glucose 6 Phosphate. The reaction begins when a basic residue deprotonates the hydroxyl group, leading to the breaking of a bond and the formation of a double bond. This process simultaneously involves the breaking of a pi bond, which captures a proton (H⁺), resulting in the formation of the enediol intermediate.

Subsequently, another basic residue deprotonates the enediol, causing further bond rearrangements. This results in the formation of a new double bond and the breaking of another pi bond, which again captures an H⁺. The final product of this transformation is a structure with a hydroxymethyl group (–CH₂OH) at the top, which rearranges to form a carbonyl group, ultimately yielding Fructose 6 Phosphate. This compound can then cyclize to form Alpha Fructose 6 Phosphate, completing the isomerization process. Understanding this mechanism is crucial for grasping the intricacies of glycolysis and the role of isomerization in metabolic pathways.

In the process of glycolysis, reaction 3 involves the phosphorylation of alpha fructose 6-phosphate, which transforms into beta fructose 1,6-bisphosphate. This reaction can be divided into two parts: reaction 3a and reaction 3b. In reaction 3a, mutarotation occurs prior to phosphorylation. During this step, alpha fructose 6-phosphate opens its cyclic structure, allowing it to convert into beta fructose 6-phosphate.

Mutarotation is facilitated by a basic residue that deprotonates, leading to the breaking of a bond. The resulting oxygen then attacks the gamma phosphorus atom through an SN2 mechanism, which results in the attachment of a phosphate group. This phosphorylation specifically occurs at carbon 1 of the fructose molecule, while the original phosphate group remains on carbon 6, hence the name beta fructose 1,6-bisphosphate.

It is important to note that during this reaction, a phosphate group is transferred from ATP, resulting in the formation of ADP. This phosphorylation step is crucial in the glycolytic pathway, as it prepares the sugar molecule for subsequent reactions, ultimately facilitating energy production in the cell.

In the process of glycolysis, bond cleavage occurs through a series of reactions involving fructose 1,6-bisphosphate. This process begins with a retro-aldol reaction, where an iminium intermediate is formed. The iminium structure is characterized by a carbon double-bonded to nitrogen, which plays a crucial role in the subsequent steps.

Initially, fructose 1,6-bisphosphate interacts with an enzyme that contains an amino group, leading to the formation of the iminium intermediate. This intermediate undergoes cleavage between carbons 3 and 4, resulting in the production of an enamine and glyceraldehyde 3-phosphate. An enamine is defined as a structure where two carbons are double-bonded, with one carbon single-bonded to a nitrogen atom.

The mechanism involves a basic residue that deprotonates the iminium, facilitating the formation of a double bond and breaking the bond between the two carbons. This reaction ultimately leads to the creation of the enamine structure, which can be further analyzed by numbering the carbon atoms involved.

Following this, the enamine undergoes tautomerization and hydrolysis, producing dihydroxyacetone phosphate (DHAP). During tautomerization, the nitrogen in the enamine forms a double bond with a carbon, resulting in the breaking of a pi bond and the addition of a proton (H⁺). This transformation yields an iminium ion, which is a protonated form of the imine, characterized by a positive charge due to its four bonds.

Finally, through hydrolysis, the iminium ion is cleaved, resulting in the formation of a carbonyl group and completing the conversion to DHAP. This series of reactions, from the formation of the iminium intermediate to the production of DHAP, illustrates the intricate bond cleavage mechanisms that are essential in glycolysis.

In the isomerization reaction of dihydroxyacetone phosphate (DHAP) to glyceraldehyde 3-phosphate (G3P), the process occurs through an indial mechanism. Initially, DHAP is acted upon by a basic residue that deprotonates a hydrogen atom, leading to the formation of a double bond. This bond rearrangement results in the breaking of a pi bond, allowing for the addition of a proton (H⁺), which temporarily forms a cis enediol intermediate.

Subsequently, another basic residue deprotonates the enediol, facilitating the formation of a new double bond. This step also involves the breaking of a pi bond and the addition of another proton, ultimately leading to the conversion of the enediol into G3P through a keto-enol tautomerism mechanism. The final structure of G3P can also be represented with the aldehyde group positioned at the top, along with a hydroxyl group (OH), an amine group (NH₂), and a methylene group (CH₂) attached to a phosphate group.

This reaction is a crucial step in glycolysis, highlighting the transformation of DHAP into a more reactive form, G3P, which plays a significant role in energy metabolism.

In glycolysis, the conversion of dihydroxyacetone phosphate (DHAP) to glyceraldehyde 3-phosphate (G3P) is a crucial step that occurs during reaction 5. This transformation is classified as an isomerization reaction, which involves the rearrangement of molecular structures without changing the overall molecular formula.

The mechanism responsible for this conversion is known as the Enediol mechanism. In this process, DHAP undergoes a series of steps that lead to the formation of an enediol intermediate, which then rearranges to yield G3P. This isomerization is significant as it allows for the utilization of both DHAP and G3P in subsequent metabolic pathways, particularly in energy production.

Understanding this mechanism is essential for grasping the broader context of glycolysis and the metabolic pathways that rely on these intermediates. The Enediol mechanism exemplifies how enzymes facilitate complex biochemical transformations efficiently, highlighting the intricate nature of metabolic regulation.

In reaction 6 of glycolysis, a significant oxidation process occurs, where glyceraldehyde 3-phosphate (G3P) is converted into 1,3-bisphosphoglycerate (1,3-BPG). This transformation involves several key steps, beginning with the formation of a hemithioacetal. Initially, a basic residue deprotonates the thiol group, leading to the cleavage of a bond that allows for a nucleophilic attack on the carbonyl carbon. This reaction results in the formation of a hemithioacetal intermediate.

Subsequently, another basic residue deprotonates the intermediate, facilitating the formation of a new carbonyl group. A hydride ion is transferred to an aldehyde, causing resonance stabilization of the resulting structure. The coenzyme NAD⁺ plays a crucial role in this oxidation process, facilitating the conversion to a thioester compound.

In the next step, the thioester undergoes a nucleophilic acyl substitution (NAS) reaction with a phosphate ion. The phosphate ion attacks the carbonyl carbon, leading to the formation of a tetrahedral intermediate. Following this, a basic residue deprotonates the intermediate, resulting in the formation of a double bond and the release of a proton. Ultimately, this series of reactions culminates in the production of 1,3-bisphosphoglycerate, a key intermediate in glycolysis.

In the context of glycolysis, Reaction 7 illustrates the process of phosphate transfer, specifically involving two molecules. The substrate 1,3-bisphosphoglycerate (1,3-BPG) is converted into 3-phosphoglycerate (3-PG) through the loss of a phosphate group. This transformation occurs via a nucleophilic acyl substitution (NAS) mechanism.

To understand this reaction, we start with 1,3-BPG, where an oxygen atom from the substrate attacks the phosphorus atom. This interaction causes the resonance of the pi bond, leading to the formation of a pentavalent intermediate. Subsequently, the attacking oxygen reforms its pi bond, which results in the breaking of the bond between the phosphorus and the original oxygen. This process ultimately yields a carboxyl group and facilitates the attachment of the phosphate group to adenosine diphosphate (ADP), resulting in the synthesis of adenosine triphosphate (ATP).

Thus, the end products of Reaction 7 in glycolysis are 3-PG and ATP, highlighting the significance of phosphate transfer in energy metabolism.

In the isomerization process of glycolysis, specifically in reaction 8, 3-phosphoglycerate (3-PG) undergoes a transformation to yield 2-phosphoglycerate (2-PG) through a series of nucleophilic acyl substitution (NAS) reactions. This transformation involves two key steps, each facilitated by a basic residue that deprotonates a hydroxyl group, leading to the breaking of a bond and the formation of a new one.

Initially, the basic residue deprotonates the hydroxyl group on 3-PG, allowing the bond to break and the electrons to shift towards the oxygen atom. Simultaneously, an oxygen atom attacks the phosphorus atom, resulting in the cleavage of a pi bond. This process is characterized by the movement of electron pairs, where a lone pair from the oxygen returns to reform the pi bond, stabilizing the structure.

As a result of these reactions, 2,3-bisphosphoglycerate (2,3-BPG) is formed, along with a freed enzyme. The enzyme then attacks the phosphorus of 2,3-BPG in a second NAS reaction, causing another pi bond to break and shift towards the oxygen. This action leads to the reformation of the pi bond and the subsequent breaking of a bond to the oxygen, which utilizes a lone pair to capture a proton (H⁺).

Ultimately, through these intricate movements of electrons and bonds, the final product of this section of glycolysis is 2-phosphoglycerate (2-PG), represented by the structure CH₂OH. This transformation is crucial for the continuation of the glycolytic pathway, highlighting the importance of enzyme-catalyzed reactions in metabolic processes.

In glycolysis, reaction 9 involves the dehydration of 2-phosphoglycerate (2-PG) to produce phosphoenolpyruvate (PEP). This reaction occurs twice, highlighting its significance in the glycolytic pathway. Magnesium ions play a crucial role in this process by helping to reduce the negative charge surrounding the 2-PG molecule, facilitating the reaction.

During this reaction, a basic residue interacts with the 2-PG. To minimize the negative charge, a deprotonation occurs, leading to the formation of a negatively charged carbon. This step is part of the E1cb mechanism, where the negatively charged carbon forms a double bond as the reaction progresses. The bond between the carbon and the hydroxyl group breaks, allowing the hydroxide ion to act as a leaving group, which is atypical since hydroxide usually does not leave easily. However, in this case, it combines with a proton (H⁺) to produce water.

The end result of this dehydration reaction is the formation of phosphoenolpyruvate (PEP), a high-energy compound that plays a vital role in subsequent steps of glycolysis. Understanding this reaction is essential for grasping the overall energy yield and regulation of glycolysis.

The final step of glycolysis, known as reaction 10, involves a crucial phosphate transfer that occurs twice. In this reaction, phosphoenolpyruvate (PEP) is converted into pyruvate through the loss of a phosphate group. This process can be described as an ATP-generating reaction, where PEP donates a phosphate group to ADP, resulting in the formation of ATP and enolpyruvate.

During this reaction, the oxygen atom from the phosphate group attacks the phosphorus atom, facilitating the movement of the bond. This is characteristic of a nucleophilic acyl substitution (NAS) reaction. The oxygen, equipped with a lone pair, subsequently returns to reform a pi bond, leading to the breaking of the bond between the phosphorus and the oxygen. Concurrently, another oxygen atom utilizes its lone pairs to capture a proton (H⁺), resulting in the formation of a hydroxyl group (–OH) in enolpyruvate.

As the reaction progresses, enolpyruvate undergoes keto-enol tautomerization, ultimately yielding pyruvate. This transformation is significant as it marks the end of glycolysis, with pyruvate being the final product. The overall reaction can be summarized as follows:

PEP + ADP → Pyruvate + ATP

This step is vital in cellular respiration, as it not only produces pyruvate, which can enter the citric acid cycle, but also generates ATP, the energy currency of the cell.