Glycolysis

Glycolysis is the metabolic process that breaks down glucose, into 2 molecules of pyruvate. Glycolysis is a central metabolic pathway that occurs in the cytoplasm of most organisms and is the first step in both aerobic and anaerobic respiration. Glycolysis is a critical process in cellular metabolism, providing energy for the cell and producing intermediates that can be used in other metabolic pathways.

What is Glycolysis?

Glycolysis is a cellular metabolic process in which glucose is broken down into pyruvate.

The Greek words glycos, which means sugar, and lysis, which means splitting, is the word glycolysis. The Gustav Embden, Otto Meyerhof, and J. Parnas-proposed glycolysis pathway are also known as the EMP pathway. It is the only mechanism of respiration in anaerobic species.

All living things undergo glycolysis, which takes place in the cell’s cytoplasm. This reaction involves the partial oxidation of glucose to produce two molecules of pyruvic acid. This glucose is produced by plants from the byproduct of photosynthesis known as sucrose. 

Glycolysis Cycle

Pathway of Glycolysis

One cycle of glycolysis is completed in 10 steps, those are:

Step 1- Hexokinase

Hexokinase is an enzyme that phosphorylates or adds a phosphate group to glucose in the cytoplasm of a cell. A phosphate group from ATP is transferred to glucose, resulting in glucose 6-phosphate, or G6P. During this phase, one molecule of ATP is consumed.

Step 2- Phosphoglucoisomerase

Phosphoglucoisomerase is an enzyme that converts G6P to its isomer fructose 6-phosphate or F6P. Isomers have the same chemical formula but differ in their atomic configurations. 

Step 3- Phosphofructokinase

The kinase phosphofructokinase transfers a phosphate group to F6P in order to create fructose 1,6-bisphosphate or FBP. So far, two ATP molecules have been used.

Step 4- Aldolase

Aldolase is an enzyme that converts fructose 1,6-bisphosphate into a ketone and an aldehyde molecule. These sugars are isomers of each other, dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (GAP).

Step 5- Triose-phosphate isomerase

The enzyme triose-phosphate isomerase transforms DHAP to GAP quickly (these isomers can inter-convert). GAP is the substrate required for glycolysis’s next step.

Step 6- Glyceraldehyde 3-phosphate dehydrogenase

In this reaction, the enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) performs two steps: 

• It dehydrogenates GAP first by transferring one of its hydrogen (H⁺) molecules to the oxidizing agent nicotinamide adenine dinucleotide (NAD⁺), resulting in NADH ⁺ H⁺.
• GAPDH combines oxidized GAP with cytosolic phosphate to generate 1,3-bisphosphoglycerate (BPG). Both molecules of GAP generated in the previous step are dehydrogenated and phosphorylated.

Step 7- Phosphoglycerokinase

To form ATP, the enzyme phosphoglycerokinase transfers a phosphate from BPG to an ADP molecule. This occurs for each BPG molecule. This process produces two molecules of 3-phosphoglycerate (3 PGA) and two molecules of ATP.

Step 8- Phosphoglycerate

To generate two 2-phosphoglycerate (2 PGA) molecules, the enzyme phosphoglyceromutase moves the P of the two 3 PGA molecules from the third to the second carbon.

Step 9- Enolase

Enolase is an enzyme that removes a molecule of water from 2-phosphoglycerate to produce phosphoenolpyruvate (PEP). This occurs for each of the two PGA molecules from Step 8.

Step 10- Pyruvate Kinase

Pyruvate and ATP are formed when the enzyme pyruvate kinase transfers a P from PEP to ADP. This occurs for each PEP molecule. This process produces two pyruvate molecules and two ATP molecules.

Energy-Requiring Phase

First, 5 steps of glycolysis are included in Energy Requiring Phase

The initial molecule of glucose is rearranged in this step, and two phosphate groups are linked to it. Because of the phosphate groups, the changed sugar, now known as fructose-1,6-bisphosphate, becomes unstable, allowing it to split in half and generate two phosphate-bearing three-carbon sugars. Two ATP molecules are utilized since the phosphates used in these are derived from ATP. 

The three-carbon sugars generated when the unstable sugar degrades are distinct from one another. Only one, glyceraldehyde-3-phosphate, can proceed to the next stage. However, the unfavorable sugar DHAP, end text, can be easily changed into the favorable one, allowing both to complete the pathway.

Energy-Releasing Phase

The last 5 steps of glycolysis are included in Energy Releasing Phase

Through a series of reactions, each three-carbon sugar is transformed into another three-carbon molecule, pyruvate, during this phase. Two ATP molecules and one NADH molecule are produced in these reactions. Because this phase occurs twice, once for each of the two three-carbon sugars, it results in four ATP and one NADH.

Each process in glycolysis has a unique enzyme that catalyzes it. Phosphofructokinase, an enzyme that catalyzes the synthesis of the unstable two-phosphate sugar molecule, is key in controlling glycolysis. fructose 1-6 bisphosphate, Phosphofructokinase speeds up or slows down glycolysis in response to the energy needs of the cell.

One six-carbon molecule of glucose is transformed into two three-carbon pyruvate molecules overall by glycolysis. Two molecules of ATP(4ATP produce- two ATP use) and 2 molecules of NADH. 

What happens to pyruvate and NADH?

End of the glycolysis cycle, two ATP, two NADH, and two pyruvate molecules were. In presence of oxygen pyruvate (oxidized) all the way to carbon dioxide in cellular respiration, making many molecules of ATP. 

What happens to the NADH? The NAD+ molecule is oxidized and remains NADH. 

NAD⁺ + 2 e- + 2 H⁺  ⇌ NADH + H ⁺ 

NAD⁺ is required for glycolysis to receive electrons as part of a specific process. If there is no NAD⁺ available (since it is entirely locked in its NADH form), this reaction cannot occur, and glycolysis is halted. To keep glycolysis functioning, all cells require a method to convert NADH to NAD+. When oxygen is present NADH pass electron to regenerate into NAD⁺ and ATP get also made. 

Total number of ATP formed and consumed in the glycolysis cycle:

4 ATPs are produced and 2NADPH are produced in glycolysis. Each NADPH gives 3 ATP molecules. 2 ATPs are utilized in glycolysis. So, net 2 ATP is produced after one glycolysis cycle.

Regulation of Glycolysis

Regulation of Hexokinase

The first irreversible stage of glycolysis is the phosphorylation of glucose by hexokinase.

• Only excess glucose-6 phosphate regulates it. If G6P accumulates in the cell, hexokinase is inhibited by feedback until the G6P is consumed.
• Other mechanisms, such as the pentose phosphate shunt and glycogen production, require glucose-6-phosphate. As a result, unless G-6-P accumulates, the hexokinase process is not blocked.
• In fact, the liver, which is where glycogen is synthesized, has a homologous enzyme called glucokinase. This has a high glucose KM. This permits the brain and muscles to use glucose before it is stored as glycogen.

Regulation of Phosphofructokinase

The rate-limiting stage in glycolysis is the phosphofructokinase step.

• This enzyme is activated by high AMP/ADP levels, whereas high ATP levels block it (energy charge). Additionally, Citrate, a TCA cycle intermediary, inhibits feed-back.
• Fructose-2,6-bisphosphate is a key phosphofructokinase positive effector. The hormone-stimulated phosphorylation of F-6-P results in the formation of F-2,6-BP. Consequently, this is an illustration of allosteric feed-forward activation.

Regulation of Pyruvate Kinase

• Regulation of glycolysis occurs at the pyruvate kinase step if it progresses past the phosphofructokinase step.
• Covalent phosphorylation inhibits pyruvate kinase activity in low-glucose circumstances.
• The pyruvate kinase process is propelled ahead if fructose 1,6 bisphosphate is produced because it functions as an allosteric feedforward activator. AMP and ADP are additional positive effectors, whereas ATP is a negative effector.
• The amino acid alanine, which is produced from pyruvate, is a catabolic inhibitor. A cell’s amount of alanine indicates whether it is anabolic. High levels of alanine suggest that the cell has enough precursors for anabolic processes, allowing catabolism—which supplies the building blocks for anabolism—to be stopped.

Key points of Glycolysis

1. Glycolysis is the process in which a glucose molecule is broken down into two molecules of pyruvate.
2. The process takes place in the cytoplasm of plant and animal cells.
3. Six enzymes are involved in the process.
4. The end products of the reaction include 2 pyruvate, 2 ATP, and 2 NADH molecules.

FAQs on Glycolysis

Q1: Are plants perform glycolysis? 

Answer:

Plant glycolysis takes place in the cytosol and plastids of both green and non-green cells, where the needs for energy and precursors might differ greatly. 

Q2: Can glycolysis occur in cells that have no mitochondria?

Answer:

Yes, glycolysis occurs in a cell that has no mitochondria. For example, RBC-Glycolysis takes place in the cytoplasm of the cell.

Q3: How does respiration relate to glycolysis?

Answer:

The initial process of cellular respiration where glucose molecules are oxidized is glycolysis. Making ATP, is followed by the Krebs cycle and oxidative phosphorylation. The primary metabolic process for cellular respiration that produces energy in the form of ATP is glycolysis.