Why is glucose phosphorylated in glycolysis

Just to give it energy? Biology Molecular Biology Basics Proteins. Apr 6, In short: To trap glucose inside the cell, to make ATP, and to facilitate enzyme binding. Explanation: Phosphorylation is very important in glycolysis for the following main reasons: 1 color blue "To trap glucose" When insulin is released from the pancreas after a meal, it signals the tissues to uptake glucose. Related questions What elements make up proteins? Figure 2. Gain a better understanding of the breakdown of glucose by glycolysis by visiting this site to see the process in action.

Two ATP molecules were used in the first half of the pathway to prepare the six-carbon ring for cleavage, so the cell has a net gain of two ATP molecules and 2 NADH molecules for its use. If the cell cannot catabolize the pyruvate molecules further, it will harvest only two ATP molecules from one molecule of glucose.

Mature mammalian red blood cells are not capable of aerobic respiration —the process in which organisms convert energy in the presence of oxygen—and glycolysis is their sole source of ATP. If glycolysis is interrupted, these cells lose their ability to maintain their sodium-potassium pumps, and eventually, they die. The last step in glycolysis will not occur if pyruvate kinase, the enzyme that catalyzes the formation of pyruvate, is not available in sufficient quantities.

In this situation, the entire glycolysis pathway will proceed, but only two ATP molecules will be made in the second half. Thus, pyruvate kinase is a rate-limiting enzyme for glycolysis.

Glycolysis is the first pathway used in the breakdown of glucose to extract energy. It was probably one of the earliest metabolic pathways to evolve and is used by nearly all of the organisms on earth. Glycolysis consists of two parts: The first part prepares the six-carbon ring of glucose for cleavage into two three-carbon sugars. ATP is invested in the process during this half to energize the separation.

Two ATP molecules are invested in the first half and four ATP molecules are formed by substrate phosphorylation during the second half.

Skip to main content. Metabolic Pathways. Search for:. Reading: Glycolysis You have read that nearly all of the energy used by living cells comes to them in the bonds of the sugar, glucose. The two phosphates in the tiny 1,3BPG molecule repel each other and give the molecule high potential energy.

This energy is utilized by the enzyme phosphoglycerate kinase another transferase to phosphorylate ADP and make ATP, as well as the product, 3-phosphoglycerate 3-PG. This is an example of a substrate-level phosphorylation. Though there are a few substrate level phosphorylations in cells including another one at the end of glycolysis , the vast major of ATP is made by oxidative phosphorylation in the mitochondria in animals.

In addition to oxidative phosphorylation, plants also make ATP by photophosphorylation in their chloroplasts. Conversion of the 3-PG intermediate to 2-PG 2- phosphoglycerate occurs by an important mechanism.

An intermediate in this readily reversible reaction catalyzed by phosphoglycerate mutase - a mutase enzyme is 2,3-BPG. This intermediate, which is stable, is released with low frequency by the enzyme instead of being con- Figure 6. The molecule can also be made from 1,3-BPG as a product of a reaction catalyzed by bisphophglycerate mutase Figure 6.

Cells which are metabolizing glucose rapidly release more 2,3-BPG and, as a result, get more oxygen, supporting their needs. Notably, cells which are metabolizing rapidly are using oxygen more rapidly and are more likely to be deficient in it.

The reaction is readily reversible, but with PEP, the cell has one of its highest energy molecules and that is important for the next reaction. Conversion of PEP to pyruvate by pyruvate kinase is the second substrate level phosphorylation of glycolysis, creating ATP. Consequently, this energy is lost as heat. If you wonder why you get hot when you exercise, the heat produced in the breakdown of glucose is a prime contributor and the pyruvate kinase reaction is a major source.

Pyruvate kinase is the third and last enzyme of glycolysis that is regulated see below. The primary reason this is the case is to be able to prevent this reaction from occurring when cells are making PEP while going through gluconeogenesis see more HERE. Though glycolysis is a pathway focused on the metabolism of glucose and fructose, the fact that other sugars can be readily metabolized into glucose means that glycolysis can be used for extracting energy from them as well.

Galactose is a good example. It is commonly produced in the produced in the body as a result of hydrolysis of lactose, catalyzed by the enzyme known as lactase Figure 6. Deficiency of lactase is the cause of lactose intolerance. Galactose begins preparation for entry into glycolysis by being converted to galactose phosphate catalyzed by galactokinase - Figure 6. Each turn of the cycle thus takes in one galactosephosphate and releases one glucosephosphate.

Deficiency of galactose conversion enzymes results in accumulation of galactose from breakdown of lactose. Excess galactose is converted to galactitol, a sugar alcohol.

Galactitol in the human eye lens causes it to absorb water and this may be a factor in formation of cataracts. First, it can be phosphorylated to fructosephosphate by hexokinase. A more interesting alternate entry point is that shown in Figure 6. Phosphorylation of fructose by fructokinase produces fructosephosphate and cleavage of that by fructose phosphate aldolase yields DHAP and glyceraldehyde.

Some have proposed this may be important when considering metabolism of high fructose corn syrup, since it forces production of pyruvate, a precursor of acetyl-CoA, which is itself a precursor of fatty acids when ATP levels are high. Mannose can also be metabolized in glycolysis. In this case, it enters via fructose by the following two-step process - 1 phosphoryla- Figure 6. Glycerol is an important molecule for the synthesis of fats, glycerophospholipids, and other membrane lipids.

Most commonly it is made into glycerol phosphate Figure 6. The relevant intermediate in these pathways both for producing and for using glycerolphosphate is DHAP. The enzyme glycerolphosphate dehydrogenase reversibly converts glycerol phosphate into DHAP Figure 6. Both glycolysis and gluconeogenesis are sources DHAP, meaning when the cell needs glycerol- 3-phosphate that it can use sugars glucose, fructose, mannose, or galactose as sources in glycolysis.

For gluconeogenesis, sources include pyruvate, alanine and Figure 6. All of the intermediates of the citric acid cycle and glyoxylate cycle can be converted ultimately to oxaloacetate, which is a gluconeogenesis intermediate, as well. It is worth noting that animals are unable to use fatty acids as materials for gluconeogenesis in net amounts, but they can, in fact, use glycerol in both glycolysis and gluconeogenesis. It is the only part of the fat molecule that can be so used.

As noted, pyruvate produced in glycolysis can be oxidized to acetyl-CoA, which is itself oxidized in the citric acid cycle to carbon dioxide.

That is not the only metabolic fate of pyruvate, though Figure 6. Thus, fermentation of pyruvate is essential to keep glycolysis operating when oxygen is limiting. It is also for these reasons that brewing of beer using yeast involves depletion of oxygen and muscles low in oxygen produce lactic acid animals. Pyruvate is a precursor of alanine which can be easily synthesized by transfer of a nitrogen from an amine donor, such as glutamic acid.

Pyruvate can also be converted into oxaloacetate by carboxylation in the process of gluconeogenesis see below. The enzymes involved in pyruvate metabolism include pyruvate dehydrogenase makes acetyl-CoA , lactate dehydrogenase makes lactate , transaminases make alanine , pyruvate carboxylase makes ox- Figure 6. When oxygen is absent, pyruvate is converted to lactate animals or ethanol bacteria and yeast.

When oxygen is present, pyruvate is converted to acetyl-CoA. Not shown - Pyruvate transamination to alanine or carboxylation to form oxaloacetate. Catalytic action and regulation of the pyruvate dehydrogenase complex is discussed in the section on the citric acid cycle HERE. The anabolic counterpart to glycolysis is gluconeogenesis Figure 6. In seven of the eleven reactions of gluconeogenesis starting from pyruvate , the same enzymes are used as in glycolysis, but the reaction directions are reversed.

Notably, pyruvate carboxylase and G6Pase are found in the mitochondria and endoplasmic reticulum, respectively, whereas the other two are found in the cytoplasm along with all of the enzymes of glycolysis. Biotin An important coenzyme used by pyruvate carboxylase is biotin Figure 6. Biotin is commonly used by carboxylases to carry CO2 to incorporate into the substrate.

Also known as vitamin H, biotin is a water soluble B vitamin B7 needed for many metabolic processes, including fatty acid synthesis, gluconeogenesis, and amino acid metabolism. Deficiency of the vitamin is rare, since it is readily produced by gut Gluconeogenesis and glycolysis. Only the enzymes differing in gluconeogenesis are shown Image by Aleia Kim teria.

There are many claims of advantages of taking biotin supplements, but there is no strong indication of benefits in most cases. Deficiencies are associated with inborn genetic errors, alcoholism, burn patients, and people who have had a gastrectomy. Some pregnant and lactating women may have reduced levels due to increased biotin catabolism.

All of the enzymes of glycolysis and nine of the eleven enzymes of gluconeogenesis are all in the cytoplasm, necessitating a coordinated means of controlling them. Cells generally need to minimize the extent to which paired anabolic and catabolic pathways are occurring simultaneously, lest they produce a futile cycle, resulting in wasted energy with no tangible product except heat. The mechanisms of controlling these pathways have opposite effects on catabolic and anabolic processes.

This method of control is called reciprocal regulation see above. Reciprocal regulation is a coordinated means of simultaneously controlling metabolic pathways that do opposite things.

The corresponding enzyme from gluconeogenesis catalyzing a reversal of the glycolysis reaction is known as F1,6BPase. In glycogen metabolism, the enzymes phosphorylase kinase and glycogen phosphorylase catalyze reactions important for the breakdown of glycogen. The enzyme glycogen synthase catalyzes the synthesis of glyco- Directional velocity Inverts with reciprocity If glycolysis is flowing Glucose synthesis awaits But when the latter is a-going Sugar breakdown then abates Figure 6.

Each of these enzymes is, at least partly, regulated by attachment and removal of phosphate. Phosphorylation of phosphorylase kinase and glycogen phosphorylase has the effect of making them more active, whereas phosphorylation of glycogen synthase makes it less active. Conversely, dephosphorylation has the reverse effects on these enzymes - phosphorylase kinase and glycogen phosphorylase become less active and glycogen synthase becomes more active.

The advantage of reciprocal regulation schemes is that they are very efficient. Further, its simplicity ensures that when one pathway is turned on, the other is turned off. A simple futile cycle is shown on Figure 6. The process will start with pyruvate and end with pyruvate, so there is no net production of molecules. Besides reciprocal regulation, other mechanisms help control gluconeogenesis. Pyruvate carboxylase is sequestered in the mitochondrion one means of regulation Figure 6.

Acetyl-CoA concentrations increase as the citric acid cycle activity decreases. Glucose phosphatase is present in low concentrations in many tissues, but is found most abundantly and importantly in the major gluconeogenic organs — the liver and kidney cortex. Control of glycolysis and gluconeogenesis is unusual for metabolic pathways, in that regulation occurs at multiple points. For glycolysis, this involves three enzymes:. Regulation of hexokinase is the simplest of these. The enzyme is unusual in being inhibited by its product, glucosephosphate.

This ensures when glycolysis is slowing down hexokinase is also slowing down to reduce feeding the pathway. It might also seem odd that pyruvate kinase, the last enzyme in the pathway, is regulated Figure 6. Pyruvate kinase catalyzes the most energetically rich reaction of glycolysis.

When cells are needing to make glu- igure 6. Consequently, pyruvate kinase must be inhibited during gluconeogenesis or a futile cycle will occur and no glucose will be made. Another interesting control mechanism called feedforward activation involves pyruvate kinase. Pyruvate kinase is activated allosterically by the glycolysis intermediate, F1,6BP. This molecule is a product of the PFK-1 reaction and a substrate for the aldolase reaction.

When this happens, some of the excess F1,6BP binds to pyruvate kinase, which activates and jump- Figure 6. PFK-1 has a complex regulation scheme. First, it is reciprocally regulated relative to F1,6BPase by three molecules. PFK-1 is also inhibited by ATP and is exquisitely sensitive to proton concentration, easily losing activity when the pH drops only slightly.

Thus, only when ATP concentration is high is binding at the allosteric site favored and only then can ATP turn off the enzyme. With respect to energy, the liver and muscles act complementarily. The liver is the major or- Figure 6. Muscles are major users of glucose to make ATP. Actively exercising muscles use oxygen faster than the blood can deliver it. As a consequence, the muscles go anaerobic and produce lactate. This lactate is of no use to muscle cells, so they dump it into the blood.

That energy is used to create ATP, as the 2-phosphoglycerate undergoes dehydration by enolase to make phosphoenolpyruvate PEP. PEP hydrolysis, on the other hand, releases significantly more than needed.

Enolpyruvate is then converted to its keto tautomer. Keeping in mind the doubling of reactions from steps splitting of fructose-1,6- bisphosphate generates two G3P , the total usable energy production from glycolysis of a single molecule of glucose is 4 ATP and 2 NADH.

Not really anything to write home about. Furthermore, although the NADH and pyruvate can participate in the tricarboxylic acid cycle in aerobic eukaryotic situations to generate a significant amount of ATP, in anaerobic situations, they do not produce usable energy. Bidirectional arrows indicate enzymes used for both glycolysis and gluconeogenesis.

Unidirectional arrows indicate enzymes that only function in glycolysis. Thus anaerobic ATP production, i. On the other hand, when a lot of ATP must be generated quickly, glycolysis is the mechanism of choice, in cells such as the fast-twitch fibers of skeletal muscle.

These cells actually have very few mitochondria because glycolysis can produce ATP at a much higher up to times rate than oxidative phosphorylation. What happens to the pyruvate and NADH? In aerobically metabolizing cells, they go to the mitochondria for the TCA cycle and oxidative phosphorylation. In anaerobes, they undergo fermentation.

This flavoprotein dehydrogenase takes the electrons from glycerolP to make FADH 2 , which can participate in the electron transport chain.