Glycolysis is a universal process among life forms on planet Earth. From the simplest one-celled bacteria to the biggest whales in the sea, all organisms – or more specifically, each one of their cells – use the six-carbon sugar molecule glucose as an energy source.
Glycolysis is the set of 10 biochemical reactions that serves as the initial step toward the complete breakdown of glucose. In many organisms, it is also the final, and therefore only, step.
In the domains Bacteria and Archaea, which together make up the mostly unicellular organisms called prokaryotes, glycolysis is the only metabolic show in town, as their cells lack the machinery to carry out cellular respiration to its completion.
Glycolysis: A Pocket Summary
The complete reaction encompassed by the individual steps of glycolysis is:
C6H12O6 + 2 NAD+ + 2 ADP + 2 Pi → 2 CH3(C=O)COOH + 2 ATP + 2 NADH + 4 H+ + 2 H2O
In words, this means that glucose, the electron carrier nicotinamide adenine dinucleotide, adenosine diphosphate and inorganic phosphate (Pi) combine to form pyruvate, adenosine triphosphate, the reduced form of nicotinamide adenine dinucleotide and hydrogen ions (which can be regarded as electrons).
Note that oxygen does not appear in this equation, because glycolysis can proceed without O2. This can be a point of confusion, because, since glycolysis is a necessary precursor to the aerobic segments of cellular respiration in eukaryotes ("aerobic" means "with oxygen"), it is often mistakenly viewed as an aerobic process.
What Is Glucose?
Glucose is a carbohydrate, meaning that its formula assumes the ratio of two hydrogen atoms for every carbon and oxygen atom: CnH2nOn. It is a sugar, and specifically a monosaccharide, meaning it cannot be split into other sugars, as can the disaccharides sucrose and galactose. It includes a six-atom ring shape, five atoms of which are carbon and one of which is oxygen.
Glucose can be stored in the body as a polymer called glycogen, which is nothing more than long chains or sheets of individual glucose molecules joined by hydrogen bonds. Glycogen is stored primarily in the liver and in muscles.
Athletes who preferentially use certain muscles (e.g., marathoners who rely on their quadriceps and calf muscles) adapt through training to store unusually high amounts of glucose, often called "carbo-loading."
Overview of Metabolism
Adenosine triphosphate (ATP) is the "energy currency" of all living cells. This means that when food is eaten and broken down into glucose before entering cells, the ultimate aim of the metabolism of glucose is the synthesis of ATP, a process driven by the energy released when the bonds in glucose and the molecules it is changed into in glycolysis and aerobic respiration are broken apart.
The ATP generated through these reactions is used for the basic, everyday needs of the body, such as tissue growth and repair as well as physical exercise. As exercise intensity increases, the body shifts away from burning fats, or triglycerides (via the oxidation of fatty acids) to burning glucose because the latter process results in more ATP created per molecule of fuel.
Enzymes at a Glance
Virtually all biochemical reactions rely on help from specialized protein molecules called enzymes to proceed.
Enzymes are catalysts, meaning that they speed up reactions – sometimes by a factor of a million or more – without themselves being changed in the reaction. They are usually named for the molecules on which they act and have "-ase" at the end, such as "phosphoglucose isomerase," which rearranges the atoms in glucose-6-phosphate to fructose-6-phosphate.
(Isomers are compounds with the same atoms but different structures, analogous to anagrams in the world of words.)
Most enzymes in human reactions conform to a "one to one" rule, meaning that each enzyme catalyzes a particular reaction, and conversely, that each reaction can only be catalyzed by one enzyme. This level of specificity helps cells tightly regulate the speed of reactions and, by extension, the amounts of different products produced in the cell at any time.
Early Glycolysis: Investment Steps
When glucose enters a cell, the first thing that that happens is that it is phosphorylated – that is, a molecule of phosphate is attached to one of the carbons in glucose. This confers a negative charge on the molecule, effectively trapping it in the cell. This glucose-6-phosphate is then isomerized as described above into fructose-6-phosphate, which then undergoes another phosphorylation step to become fructose-1,6-bisphosphate.
Each of the phosphorylation steps involves the removal of a phosphate from ATP, leaving adenosine diphosphate (ADP) behind. This means that although the aim of glycolysis is to produce ATP for the cell's use, it involves a "start-up cost" of 2 ATP per glucose molecule entering the cycle.
Fructose-1,6-bisphosphate is then split into two three-carbon molecules, each with its own phosphate attached. One of these, dihydroxyacetone phosphate (DHAP), is short-lived, as it is quickly transformed into the other, glyceraldehyde-3-phosphate. Thus from this point forward, every reaction listed actually occurs twice for every glucose molecule entering glycolysis.
Later Glycolysis: Payoff Steps
Glyceraldehyde-3-phosphate is converted into 1,3-diphosphoglycerate by the addition of a phosphate to the molecule. Rather than being derived from ATP, this phosphate exists as a free, or inorganic (i.e., lacking a bond to carbon) phosphate. At the same time, NAD+ is converted to NADH.
In the next steps, the two phosphates are stripped from a series of three-carbon molecules and appended to ADP to generate ATP. Because this happens twice per original glucose molecule, a total of 4 ATP are created in this "payoff" phase. Because the "investment" phase required an input of 2 ATP, the overall gain in ATP per glucose molecule is 2 ATP.
For reference, after 1,3-diphosphoglycerate, the molecules in the reaction are 3-phosphoglycerate, 3-phosphoglycerate, phosphoenolpyruvate and finally pyruvate.
The Fate of Pyruvate
In eukaryotes, pyruvate may then proceed to one of two post-glycolysis pathways, depending on whether enough oxygen is present to allow aerobic respiration to proceed. If it is, which is usually the case when the parent organism is resting or exercising lightly, the pyruvate is shuttled from the cytoplasm where glycolysis occurs into organelles ("little organs") called mitochondria.
If the cell belongs to a prokaryote or to a very hard-working eukaryote – say, a human who is running an all-out half-mile or lifting weights intensely – pyruvate is converted to lactate. While in most cells lactate itself cannot be used as fuel, this reaction creates NAD+ from NADH, thereby allowing glycolysis to continue "upstream" by supplying a critical source of NAD+.
This process is known as lactic acid fermentation.
Footnote: Aerobic Respiration in Brief
The aerobic phases of cellular respiration that take place in mitochondria are called the Krebs cycle and the electron transport chain, and these occur in that order. The Krebs cycle (often called the citric acid cycle or the tricarboxylic acid cycle) unfolds in the middle of the mitochondria, whereas the electron transport chain takes places on the membrane of the mitochondria that forms its boundary with the cytoplasm.
The net reaction of cellular respiration, including glycolysis, is:
C6H12O6 + 6 O2 → 6 CO2 + 6 H2O + 38 ATP
The Krebs cycle adds 2 ATP, and the electron transport chain a whopping 34 ATP for a total of 38 ATP per molecule of glucose completely consumed (2 + 2 + 34) in the three metabolic processes.
- NCBI Bookshelf: StatPearls: Biochemistry, Glycolysis
- Georgia State University: HyperPhysics: Glycolysis
- IUPUI Department of Biology: Cellular Respiration
- Scitable by Nature Education: Cell Metabolism
- Biology LibreTexts: Regulation of Metabolic Pathways A – How Is Enzyme Activity Regulated?
- Auburn University Biology Department: How Do Cells Harvest Energy?