OpenStax Anatomy and Physiology
Glucose is the body’s most readily available source of energy. After digestive processes break polysaccharides down into monosaccharides, including glucose, the monosaccharides are transported across the wall of the small intestine and into the circulatory system, which transports them to the liver. In the liver, hepatocytes either pass the glucose on through the circulatory system or store excess glucose as glycogen. Cells in the body take up the circulating glucose in response to insulin and, through a series of reactions called glycolysis, transfer some of the energy in glucose to ADP to form ATP. The last step in glycolysis produces the product pyruvate.
Glycolysis begins with the phosphorylation of glucose by hexokinase to form glucose-6-phosphate. This step uses one ATP, which is the donor of the phosphate group. Under the action of phosphofructokinase, glucose-6-phosphate is converted into fructose-6-phosphate. At this point, a second ATP donates its phosphate group, forming fructose-1,6-bisphosphate. This six-carbon sugar is split to form two phosphorylated three-carbon molecules, glyceraldehyde-3-phosphate and dihydroxyacetone phosphate, which are both converted into glyceraldehyde-3-phosphate. The glyceraldehyde-3-phosphate is further phosphorylated with groups donated by dihydrogen phosphate present in the cell to form the three-carbon molecule 1,3-bisphosphoglycerate. The energy of this reaction comes from the oxidation of (removal of electrons from) glyceraldehyde-3-phosphate. In a series of reactions leading to pyruvate, the two phosphate groups are then transferred to two ADPs to form two ATPs. Thus, glycolysis uses two ATPs but generates four ATPs, yielding a net gain of two ATPs and two molecules of pyruvate. In the presence of oxygen, pyruvate continues on to the Krebs cycle (also called the citric acid cycle or tricarboxylic acid cycle (TCA), where additional energy is extracted and passed on.
Glycolysis can be divided into two phases: energy consuming (also called chemical priming) and energy yielding. The first phase is the energy-consuming phase, so it requires two ATP molecules to start the reaction for each molecule of glucose. However, the end of the reaction produces four ATPs, resulting in a net gain of two ATP energy molecules. Glycolysis can be expressed as the following equation:
This equation states that glucose, in combination with ATP (the energy source), NAD+ (a coenzyme that serves as an electron acceptor), and inorganic phosphate, breaks down into two pyruvate molecules, generating four ATP molecules—for a net yield of two ATP—and two energy-containing NADH coenzymes. The NADH that is produced in this process will be used later to produce ATP in the mitochondria. Importantly, by the end of this process, one glucose molecule generates two pyruvate molecules, two high-energy ATP molecules, and two electron-carrying NADH molecules.
When glucose enters a cell, the enzyme hexokinase (or glucokinase, in the liver) rapidly adds a phosphate to convert it into glucose-6-phosphate. A kinase is a type of enzyme that adds a phosphate molecule to a substrate (in this case, glucose, but it can be true of other molecules also). This conversion step requires one ATP and essentially traps the glucose in the cell, preventing it from passing back through the plasma membrane, thus allowing glycolysis to proceed. It also functions to maintain a concentration gradient with higher glucose levels in the blood than in the tissues. By establishing this concentration gradient, the glucose in the blood will be able to flow from an area of high concentration (the blood) into an area of low concentration (the tissues) to be either used or stored. Hexokinase is found in nearly every tissue in the body. Glucokinase, on the other hand, is expressed in tissues that are active when blood glucose levels are high, such as the liver. Hexokinase has a higher affinity for glucose than glucokinase and therefore is able to convert glucose at a faster rate than glucokinase. This is important when levels of glucose are very low in the body, as it allows glucose to travel preferentially to those tissues that require it more.
In the next step of the first phase of glycolysis, the enzyme glucose-6-phosphate isomerase converts glucose-6-phosphate into fructose-6-phosphate. Like glucose, fructose is also a six carbon-containing sugar. The enzyme phosphofructokinase-1 then adds one more phosphate to convert fructose-6-phosphate into fructose-1-6-bisphosphate, another six-carbon sugar, using another ATP molecule. Aldolase then breaks down this fructose-1-6-bisphosphate into two three-carbon molecules, glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. The triosephosphate isomerase enzyme then converts dihydroxyacetone phosphate into a second glyceraldehyde-3-phosphate molecule. Therefore, by the end of this chemicalpriming or energy-consuming phase, one glucose molecule is broken down into two glyceraldehyde-3-phosphate molecules.
The second phase of glycolysis, the energy-yielding phase, creates the energy that is the product of glycolysis. Glyceraldehyde-3-phosphate dehydrogenase converts each three-carbon glyceraldehyde-3-phosphate produced during the energy-consuming phase into 1,3-bisphosphoglycerate. This reaction releases an electron that is then picked up by NAD+ to create an NADH molecule. NADH is a high-energy molecule, like ATP, but unlike ATP, it is not used as energy currency by the cell. Because there are two glyceraldehyde-3-phosphate molecules, two NADH molecules are synthesized during this step. Each 1,3-bisphosphoglycerate is subsequently dephosphorylated (i.e., a phosphate is removed) by phosphoglycerate kinase into 3-phosphoglycerate. Each phosphate released in this reaction can convert one molecule of ADP into one highenergy ATP molecule, resulting in a gain of two ATP molecules.
The enzyme phosphoglycerate mutase then converts the 3-phosphoglycerate molecules into 2-phosphoglycerate. The enolase enzyme then acts upon the 2-phosphoglycerate molecules to convert them into phosphoenolpyruvate molecules. The last step of glycolysis involves the dephosphorylation of the two phosphoenolpyruvate molecules by pyruvate kinase to create two pyruvate molecules and two ATP molecules.
In summary, one glucose molecule breaks down into two pyruvate molecules, and creates two net ATP molecules and two NADH molecules by glycolysis. Therefore, glycolysis generates energy for the cell and creates pyruvate molecules that can be processed further through the aerobic Krebs cycle (also called the citric acid cycle or tricarboxylic acid cycle); converted into lactic acid or alcohol (in yeast) by fermentation; or used later for the synthesis of glucose through gluconeogenesis.
Betts, J. G., Young, K. A., Wise, J. A., Johnson, E., Poe, B., Kruse, D. H., … DeSaix, P. (n.d.). Anatomy and Physiology. Houston, Texas: OpenStax. Access for free at: https://openstax.org/details/books/anatomy-and-physiology