Hi, and welcome to this Article on glycolysis. Glycolysis takes place in the cytoplasm of a cell as the first phase in cellular respiration of the Kreb’s cycle. When glycolysis appears, it cracks down glucose into pyruvic acids in the cytoplasm.
Commonly speaking, glycolysis is something that appears inside the body to process food. But what does this action look like, and how does it work? Let’s take a look! Metabolism arrives from the Greek root that indicates “change.” Our bodies reform food into applicable energy for our cells. But we eat all types of food that contain all types of nutrients, so how do our bodies know how to crack everything down?
First, let’s look at this mostly. There are two pathways our body manages to metabolize nutrients. If our body breaks down stuff into its macromolecules, we analyze it as a catabolic pathway. This process discharges energy in the form of ATP. If our body evolves up more complex molecules from other simpler precursors, we recognize it as an anabolic pathway, which demands energy to complete.
Today we are going to describe a definite type of catabolic reaction called glycolysis. Glycolysis is used for breaking down a familiar carbohydrate called glucose into effective energy for the body.
Since an enormous part of our diet consists of glucose, this is the primary process for energy manufacturing in our cells. Glucose is also the only fuel for the brain under non-starving situations, the only fuel for red blood cells, and the most durable hexose so it has a low tendency to customize proteins, making it a great primary energy source.
In order to give you some background, it’s essential to note that glycolysis is part of a larger mechanism called cellular respiration that associates glycolysis, the Krebs cycle, the electron transport chain, and ATP synthase. Our scope for today’s article will concentrate only on glycolysis, which is the first step in this larger process. Glycolysis occurs in the cytoplasm and associates two stages which break up glucose – a 6-carbon molecule.
While the energy output of glycolysis is, molecule for molecule, far less than that achieved from aerobic respiration – two ATP per glucose molecule consumed for glycolysis alone vs. 36 to 38 for all of the reactions of cellular respiration associated – it is nevertheless one of nature’s most omnipresent and dependable processes in the sense that all cells use it, even if not all of them can build completely on it for their energy needs.
What is Glycolysis And Where Does Glycolysis Occur?
Glycolysis is the first stage of cellular respiration. It takes place in the cytoplasm where associated enzymes and factors are established. This process is anaerobic and therefore does not call for energy. As such, it has been shown to be one of the most antique metabolic pathways that could occur even in the most classic cells (earliest prokaryotic cells).
Glycolysis is an energy conversion pathway that occurs in almost all cells and means the breakdown of glucose into pyruvate in a series of 10 steps. These steps can be broken into three stages. Stage 1 is the capturing of glucose and destabilizing it to occur the breakdown. Step 2 is the formation of two interchangeable carbon molecules.
Stage 3 is the final stage that leads to the production of energy in the form of adenosine triphosphate (ATP). Cells that use cellular respiration uses glycolysis as the first procedure in this process. Glycolysis does not require oxygen and so can be used by anaerobic organisms for their own energy formation processes.
In stages 1 and 2, glucose is converted into fructose-1,6-bisphosphate, a fructose sugar with two phosphates added to it, using energy and a few enzymes to ease the process. This new fructose compound is turned into two interconvertible compounds. The two compounds finally settle into one compound, glyceraldehyde-3-phosphate, and then go into the final phase of energy generation.
This stage uses enzymes and some energy to create pyruvate and ATP. This stage happens twice so the final product is 2 pyruvate and 4 ATP molecules. From here, the energy is used for other processes in the cells and even the pyruvate is used.
If the organism is aerobic, like us, then the pyruvate will arrive at the citric acid cycle (CAC), which is also known as the TCA cycle. This cycle is the discharge of stored energy in compounds like carbohydrates, fats, and proteins. This all builds things like ATP. If the organism is anaerobic, when there is no oxygen, then the pyruvate is sent into a process like fermentation to build more energy for the cells.
While this is a glucose-based pathway, other sugars can be used. Galactose and fructose can be used instead of glucose because they can be turned into the changed fructose product that is the result of stage 1. Lactose can also be used because it can be turned into glucose and galactose using lactase enzyme.
Like all elements in our cells, glycolysis is a coordinated process because sometimes we need more or less energy, and the action must be slowed or increased. The cell administers these using operations that influence the synthesis of the enzymes used in glycolysis. While glycolysis is a very important part of our function, and therefore more protected against problems like mutations and disease, problems do occur.
One such complication is pyruvate kinase deficiency, which is a rooted disorder that results in reduced pyruvate kinase, the enzyme responsible for turning the final carbon admixture in glycolysis into pyruvate and ATP. This primarily affects red blood cells and can attend to things like anemia, fatigue, jaundice, and gallstones. Most people do not need hospitalization because the body can manage and counteract the problem. Those that do need treatment can get blood transfers or bone marrow transfers. There is no cure and treatments only reduce the symptoms.
Glycolysis is disturbed in many cancers as tumor cells show a higher rate of glycolysis, leading to expanded energy production. This is understandable because cancers advance at such high rates and need a lot of energy to sustain themselves. Hopefully, with more research into the relationship between glycolysis and cancer, we may be able to develop diagnosis and treatment choices for individuals with cancer cells. We are still advancing our knowledge about glycolysis and over time, we may even be able to add to it as scientists in the past did.
What Is The Cytosol?
The cytosol, or cytoplasmic matrix, is the aqua that makes up the bulk of a cell and is the place where many distinct organelles lie. It is the hub of metabolic action for many organisms and is actually a large room where different offices are established, to put it into easily visualized terms. The cytosol is made up of main water with ions and proteins in it.
These aggregates may be used for other processes and pathways or they may be traveling to different components of the cell. The cytosol does not have any functions of its own except to hold the distinct organelles and be the space that is used by metabolic mechanisms. In prokaryotes, like bacteria, metabolism happens mainly in the cytosol. In eukaryotes, like us, metabolism is broken between the cytosol and organelles. Some of those metabolic pathways include things like protein biosynthesis, the pentose phosphate pathway, gluconeogenesis, and glycolysis.
Function
Glycolysis appears in the cytosol of the cell. It is a metabolic pathway that builds ATP without the use of oxygen but can occur in the presence of oxygen as well. In cells that apply aerobic respiration as the primary source of energy, the pyruvate constructed from the pathway can be used in the citric acid cycle and go through oxidative phosphorylation to undergo oxidation into carbon dioxide and water.
Even if cells principally use oxidative phosphorylation, glycolysis can serve as an accident backup for energy or serve as the preparation phase before oxidative phosphorylation. In highly oxidative tissue, such as the heart, the construction of pyruvate is essential for acetyl-CoA synthesis and L-malate synthesis. It serves as a precursor to many molecules, such as lactate, alanine, and oxaloacetate.
Glycolysis precedes lactic acid fermentation; the pyruvate formed in the former process delivers as the essential for the lactate made in the latter process. Lactic acid fermentation is the elementary source of ATP in animal tissues with low metabolic requirements and little to no mitochondria.
In erythrocytes, lactic acid fermentation is the exclusive source of ATP, as they lack mitochondria and mature red blood cells have a little claim for ATP. Another part of the body that relies entirely or almost entirely on anaerobic glycolysis is the lens of the eye, which is devoid of mitochondria, as their presence would lead to light scattering.
Though skeletal muscles promote to catalyze glucose into carbon dioxide and water during heavy exercise where the amount of oxygen is inadequate, the muscles together undergo anaerobic glycolysis along with oxidative phosphorylation.
Regulation
- Glucose: The amount of glucose usable for the action regulates glycolysis, which becomes available primarily in two ways: regulation of glucose reuptake or regulation of the disintegration of glycogen. Glucose transporters (GLUT) shipment glucose from the outside of the cell to the inside. Cells that consist of GLUT can increase the number of GLUT in the plasma membrane of the cell from the intracellular matrix, therefore increasing the uptake of glucose and the inventory of glucose available for glycolysis. There are five types of GLUTs. GLUT1 is present in RBCs, the blood-brain barrier, and the blood-placental barrier. GLUT2 is in the liver, beta-cells of the pancreas, kidney, and gastrointestinal (GI) tract. GLUT3 is present in neurons. GLUT4 is in adipocytes, heart, and skeletal muscle. GLUT5 specifically carries fructose into cells. Another form of regulation is the breakdown of glycogen. Cells can store added glucose in the form of glycogen when glucose levels are high in the cell plasma. Conversely, when levels are low, glycogen can be modified back into glucose. Two enzymes control the disintegration of glycogen: glycogen phosphorylase and glycogen synthase. The enzymes can be administered through feedback loops of glucose or glucose 1-phosphate, or via allosteric regulation by metabolites, or from phosphorylation/dephosphorylation control.
- Allosteric Regulators and Oxygen: As defined before, many enzymes are involved in the glycolytic pathway by modifying one intermediate to another. Control of these enzymes, such as hexokinase, phosphofructokinase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase, can administer glycolysis. The amount of oxygen available can also regulate glycolysis. The “Pasteur effect” describes how the availability of oxygen abates the effect of glycolysis, and decreased availability leads to an acceleration of glycolysis, at least initially. The mechanisms responsible for this consequence include the involvement of allosteric regulators of glycolysis (enzymes such as hexokinase). The “Pasteur effect” arrives to mostly occur in tissue with high mitochondrial capacities, such as myocytes or hepatocytes, but this effect is not universal in oxidative tissue, such as pancreatic cells.
- Enzyme Induction: Another mechanism for administering glycolytic rates is transcriptional control of glycolytic enzymes. Altering the concentration of key enzymes grants the cell to change and adapt to alterations in hormonal status. For example, advancing glucose and insulin levels can increase the activity of hexokinase and pyruvate kinase, therefore increasing the production of pyruvate.
- PFK-1: Fructose 2,6-bisphosphate is an allosteric regulator of PFK-1. High levels of fructose 2,6-bisphosphate increase the activity of PFK-1. Its production arises through the action of phosphofructokinase-2 (PFK-2). PFK-2 has both kinase and phosphorylase activity and can convert fructose 6 phosphates to fructose 2,6-bisphosphate and vice versa. Insulin dephosphorylates PFK-2, and this mobilizes its kinase activity, which advances levels of fructose 2,6-bisphosphate, which subsequently goes on to activate PFK-1. Glucagon can also phosphorylate PFK-2, and this activates phosphatase, which transforms fructose 2,6-bisphosphate back to fructose 6-phosphate. This reaction decreases fructose 2,6-bisphosphate levels and decreases PFK-1 activity.
Mechanism: Glycolysis Phases
Glycolysis has two stages: the investment stage and the payoff stage. The investment stage is where there is energy as ATP put in, and the payoff stage is where the net creation of ATP and NADH molecules takes place. A total of 2 ATP goes in the investment phase, with the production of a total of 4 ATP resulting in the payoff phase; thus, there is a net total of 2 ATP. The stags by which is new ATP is created have the name substrate-level phosphorylation.
Investment Phase
In this stage, there are two phosphates added to glucose. Glycolysis begins with hexokinase phosphorylating glucose into glucose-6 phosphate (G6P). This stage is the first transfer of a phosphate group and where the consumption of the first ATP takes place. Also, this is an irreversible stage. This phosphorylation traps the glucose molecule in the cell because it cannot readily pass the cell membrane.
From there, phosphoglucose isomerase isomerizes G6P into fructose 6-phosphate (F6P). Then, phosphofructokinase (PFK-1) adds the second phosphate. PFK-1 uses the second ATP and phosphorylates the F6P into fructose 1,6-bisphosphate. This stage is also irreversible and is the rate-limiting stage.
In the following stage, fructose 1,6-bisphosphate undergoes lysis into two molecules, which then are substrates for fructose-bisphosphate aldolase to convert it into dihydroxyacetone phosphate (DHAP) and glyceraldehyde 3-phosphate (G3P). DHAP is turned into G3P by triosephosphate isomerase. DHAP and G3p are in equilibrium with each other, meaning they transform back and forth.
Payoff Phase
It is critical to remember that in this stage, there are a total of two 3-carbon sugars for every one glucose in the beginning. The enzyme glyceraldehyde-3-phosphate dehydrogenase metabolizes the G3P into 1,3-diphosphoglycerate by reducing NAD+ into NADH. Next, the 1,3-diphosphoglycerate loses a phosphate group by way of phosphoglycerate kinase to make 3-phosphoglycerate and creates an ATP through substrate-level phosphorylation.
At this point, there are 2 ATP produced, one from each 3-carbon molecule. The 3-phosphoglycerate turns into 2-phosphoglycerate by phosphoglycerate mutase, and then enolase turns the 2-phosphoglycerate into phosphoenolpyruvate (PEP). In the final stage, pyruvate kinase turns PEP into pyruvate and phosphorylates ADP into ATP through substrate-level phosphorylation, thus creating two more ATP. This stage is also irreversible. Overall, the input for 1 glucose molecule is 2 ATP, and the output is 4 ATP and 2 NADH and 2 pyruvate molecules.
In cells, NADH must recycle back to NAD+ to permit glycolysis to keep running. Absent NAD+, the payoff stage will come to a halt resulting in a backup in glycolysis. In aerobic cells, NADH recycles back into NAD+ by way of oxidative phosphorylation. In aerobic cells, it occurs through fermentation. There are two types of fermentation: lactic acid and alcohol fermentation.
Reactants and Products of Glycolysis
Glycolysis is an anaerobic process, meaning that it does not require oxygen. Be careful not to confuse “anaerobic” with “occurs only in anaerobic organisms.” Glycolysis occurs in the cytoplasm of both prokaryotic and eukaryotic cells.
It starts when glucose, which has the formula C6H12O6 and a molecular mass of 180.156 grams, diffuses into a cell through the plasma membrane down its concentration gradient.
When this happens, the number-six glucose carbon, which sits outside the primary hexagonal ring of the molecule, immediately becomes phosphorylated (i.e., has a phosphate group attached to it). The phosphorylation of glucose makes the molecule glucose-6-phosphate (G6P) electrically negative and thus traps it inside the cell.
After another nine reactions and an investment of energy, the products of glycolysis appear two molecules of pyruvate (C3H8O6) plus a pair of hydrogen ions and two molecules of NADH, an “electron carrier” that is crucial in the “downstream” reactions of aerobic respiration, which occur in the mitochondria.
Glycolysis Equation
The net equation for the reactions of glycolysis may be written like this:
C6H12O6 + 2 Pi + 2 ADP + 2 NAD+→ 2 C3H4O3 + 2 H+ + 2 NADH + 2 ATP
Here, Pi represents free phosphate and ADP stands for adenosine diphosphate, the nucleotide that serves as the direct precursor of most of the ATP in the body.
Clinical Significance
Pyruvate kinase deficiency is an autosomal recessive mutation that causes hemolytic anemia. There is an inability to form ATP and causes cell damage. Cells become swollen and are taken up by the spleen, causing splenomegaly. Signs and symptoms include jaundice, icterus, elevated bilirubin, and splenomegaly.
Arsenic poisoning also prevents ATP synthesis because arsenic takes the place of phosphate in the stages of glycolysis.
Conclusion
To summarize, glycolysis occurs in the cytoplasm to break up glucose by cleaving it into two phosphorylated 3-carbon compounds and then oxidizing these compounds to form pyruvate and net two molecules of ATP.
I hope this review was helpful! Thanks for reading, and happy studying!