In this article, we will explore what glycolysis is, how it works, and why it is crucial for cells. We will break down the steps of glycolysis, present a clear glycolysis cycle diagram, and discuss the overall glycolysis structure. By the end, you will understand the process of glycolysis and how the glycolysis pathway fits into larger metabolic processes such as cellular respiration.
Glycolysis is a fundamental biochemical reaction where a single glucose molecule (a six-carbon sugar) is broken down into two molecules of pyruvate (a three-carbon compound). During this process, cells generate a small but essential amount of energy in the form of ATP (adenosine triphosphate) and reduce NAD⁺ to NADH. Although people often refer to it as the glycolysis cycle, it is a linear pathway rather than a cycle.
Here are some key points that define what glycolysis is:
It occurs in the cytoplasm of cells.
It does not require oxygen (it is anaerobic), allowing both aerobic and anaerobic organisms to utilise it.
The net energy yield includes 2 ATP molecules and 2 NADH molecules per glucose.
Read More: TCA Cycle
Aerobic conditions: If oxygen is present, pyruvate produced by glycolysis enters the mitochondria, where it is further oxidised via the Krebs cycle (also known as the TCA cycle).
Anaerobic conditions: If oxygen is absent or limited, pyruvate may be metabolised by fermentation (e.g., lactic acid fermentation in muscle cells or alcoholic fermentation in yeast).
The glycolysis pathway is composed of ten enzyme-mediated reactions. Even though some textbooks informally refer to it as a glycolysis cycle, it is a sequence of linear steps rather than a circular route. Each step is carefully regulated to ensure efficient energy production. Below is a concise outline:
Phosphorylation of Glucose
Isomerisation of Glucose-6-phosphate
Phosphorylation to Fructose 1,6-bisphosphate
Cleavage into Two Three-Carbon Molecules
Isomerisation to Glyceraldehyde 3-phosphate
Oxidation and Phosphate Addition
ATP Formation
Shift of Phosphate Group
Dehydration
Final Formation of Pyruvate and ATP
We will explore these steps of glycolysis in detail to illustrate the process of glycolysis from start to finish.
Let us walk through each step of the glycolysis structure to see how the cell converts glucose into pyruvate:
Phosphorylation of Glucose
Enzyme: Hexokinase
Action: Transfers a phosphate group from ATP to glucose, forming glucose-6-phosphate.
Isomerisation
Enzyme: Phosphoglucose isomerase (often called phosphoglucomutase in some texts)
Action: Converts glucose-6-phosphate into fructose-6-phosphate.
Second Phosphorylation
Enzyme: Phosphofructokinase (PFK)
Action: Adds another phosphate from ATP to fructose-6-phosphate, creating fructose-1,6-bisphosphate.
Note: PFK is a key regulatory enzyme in the glycolysis pathway.
Cleavage
Enzyme: Aldolase
Action: Splits fructose-1,6-bisphosphate into two three-carbon molecules: glyceraldehyde-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).
Isomerisation of DHAP
Enzyme: Triose phosphate isomerase
Action: Converts DHAP into another G3P, so now there are two G3P molecules.
Oxidation & Phosphate Addition
Enzyme: Glyceraldehyde-3-phosphate dehydrogenase
Action: Oxidises G3P and adds an inorganic phosphate, producing 1,3-bisphosphoglycerate and NADH (from NAD⁺).
First ATP Formation
Enzyme: Phosphoglycerate kinase
Action: Transfers a phosphate from 1,3-bisphosphoglycerate to ADP, forming ATP and 3-phosphoglycerate.
Relocation of Phosphate
Enzyme: Phosphoglyceromutase
Action: Moves the phosphate group from the third carbon to the second carbon, converting 3-phosphoglycerate into 2-phosphoglycerate.
Dehydration
Enzyme: Enolase
Action: Removes a water molecule from 2-phosphoglycerate, resulting in phosphoenolpyruvate (PEP).
Second ATP Formation
Enzyme: Pyruvate kinase
Action: Transfers the phosphate from PEP to ADP, generating ATP and pyruvate.
Result: Two molecules of pyruvate, two molecules of ATP (net gain), and two molecules of NADH per glucose.
Read More: Difference Between Glycolysis and Kreb’s Cycle
Energy Supply: Glycolysis provides a quick source of energy, producing ATP even without oxygen.
Universal Pathway: It is present in almost all organisms, from simple bacteria to complex plants and animals.
Metabolic Hub: The pyruvate formed can either enter the Krebs cycle in aerobic conditions or undergo fermentation in anaerobic conditions.
Clinical Relevance: Some cancer cells exhibit increased glycolytic rates (known as the Warburg effect), illustrating the pathway’s importance in medical research.
Red Blood Cells: Mature RBCs rely exclusively on glycolysis for ATP, as they lack mitochondria.
By looking closely at the glycolysis pathway, we gain insights into several regulatory mechanisms and related pathways:
Regulatory Enzymes: Key enzymes like hexokinase, phosphofructokinase (PFK), and pyruvate kinase are tightly controlled by levels of ATP, AMP, and other metabolites to ensure balanced energy production.
Alternate Fates of Pyruvate: Pyruvate can be converted into lactate under anaerobic conditions or funnelled into the Krebs cycle for further ATP production when oxygen is abundant.
Shuttle Systems: NADH generated in the cytoplasm is often transported into mitochondria through shuttle systems (e.g., malate-aspartate shuttle), especially in eukaryotic cells.
The process of glycolysis is central to all living organisms. By exploring what glycolysis is, reviewing the steps of glycolysis, and visualising the glycolysis cycle diagram, we see how glucose is systematically converted into pyruvate to yield energy. Although people sometimes refer to a “glycolysis cycle,” it is more accurately a straightforward sequence of reactions and a crucial foundation for further energy-generating pathways. With regulatory checkpoints and multiple branching points, glycolysis stands as a vital and elegantly controlled metabolic route.
1. Is glycolysis the same as the Krebs cycle?
No, they are distinct processes. Glycolysis happens in the cytoplasm without requiring oxygen, while the Krebs cycle occurs in the mitochondria under aerobic conditions.
2. Why is glycolysis sometimes called the glycolysis cycle?
It is a misnomer. Glycolysis is not a cycle but a linear pathway. The term “glycolysis cycle” is sometimes used informally when referencing diagrams, but the correct term is “glycolysis pathway.”
3. How many ATP molecules are produced by glycolysis?
The net ATP gain is two molecules per glucose. Four ATP are formed, but two are used during the early steps, resulting in a net gain of two.
4. What happens to NADH produced during glycolysis?
Under aerobic conditions, NADH goes into the electron transport chain in the mitochondria to generate more ATP. Under anaerobic conditions, NADH is used to convert pyruvate into lactate or ethanol, depending on the organism.
5. Why study the steps of glycolysis in detail?
Understanding every step highlights how cells control energy flow, how metabolic disorders can arise, and how certain drugs or toxins might affect cellular function.