Glycogen

Glycogen

Biopolymer homoglycan

Odorless crystalline powder ( beige )

Fixed

270-280 ° C ( decomposition)

Soluble in water

The glycogen ( also glycogen, animal starch or starch liver ) is a branched polysaccharide ( multiple sugar), which is composed of glucose units. Glycogen is the short-to medium-term storage and availability of the energy source of glucose in the human and animal organism. Fungi use this form of energy storage, while plants use starch as a carbohydrate storage. The process of building glycogen is called glycogen synthesis, the reverse process of glycogen breakdown as glycogenolysis.

In liver and muscle glycogen is established when a surplus of carbohydrates whose mass fraction is in the liver to 20 %. With regard to increased energy demand the muscle cells use their glycogen stores. Also stored in the liver and kidney glycogen is broken down to glucose again when needed, which in this case glucose is made ​​available to the whole organism to dispose of the blood.

Structure of glycogen

Glycogen consists of a central protein ( glycogenin ), to which up to 50,000 glucose units are usually α -1 ,4- glycosidically linked. Every 8-12 Glucose-/Monosaccharid-Bausteine ​​occurs in addition to the α -1 ,4- glycosidic bond, a further α -1 ,6- glycosidic linkage, whereby the molecule is branched like a tree. Thus, glycogen can be broken down into glucose in many different locations as needed within a molecule. Amylopectin, a component of plant starch, is constructed exactly as glycogen, however, has a lower degree of branching, as only about 25 of each glucose molecule having a 1,6- glycosidic linkage. The Molar mass of glycogen is about 106-107 daltons.

Glycogen metabolism in the human

With the food taken strength by the enzyme alpha -amylase ( ptyalin accurate ) is digested in the mouth and in the duodenum in the two disaccharides maltose and isomaltose, which in turn are eventually converted by enzymes into glucose.

The muscle glycogen exclusively uses its own, the liver and kidneys serve as glycogen and put it mainly other cells. This is especially important in the sleep state as an energy supply for cells of the adrenal medulla and erythrocytes because these cells are dependent on glucose as an energy supplier.

The blood sugar level is regulated, among other means Glykogenauf and degradation by different hormones: adrenaline and glucagon stimulate glycogen breakdown, insulin promotes the Glykogenaufbau. Insulin and glucagon are made in parts of the pancreas. The glycogen content of the liver varies depending on the nutritional status of the human body. In the fasting state, it is less than 1% of liver weight. In good nutritional status and carbohydrate- rich diet it can grow to 10% of the liver weight. Calculated per gram of tissue glycogen capacity of the kidney is higher than that of the liver. However, since the liver is the major organ significantly, the absolute capacity of the liver is higher.

Glycogen synthesis

For the synthesis of a glycogen molecule in each case a so-called core protein is required. This called glycogenin molecule forms the center of each glycogen molecule. It has even some molecules α -1 ,4- glycosidically linked glucose required of glycogen synthase as a primer - this enzyme slides as the slider of a zipper to the existing chain of glucose molecules along and can not determine a start point itself.

Glucose comes in body cells hardly in its free form but is phosphorylated at its 6- carbon atom, so it does not diffuse out through the cell membrane and can also be easily metabolised. Thus the so-called glucose -6-phosphate can be fitted to existing glycogen, it must first by the enzyme phosphoglucomutase to glucose -1-phosphate isomerized and subsequently activated by uridine triphosphate - the result is UDP -glucose and free pyrophosphate, to drive the synthesis of the is quickly broken down further into two inorganic (i = inorganic ) phosphate molecules. This activation is catalysed by the enzyme UDP-glucose pyrophosphorylase, and follows the following equation:

The activated glucose is then added through the glycogen synthase to the primer or the existing Glykogenkette at the non- reducing end:

While the glycogen synthase generates a long chain, another enzyme is responsible for the branch: the 1,4- α -glucan branching enzyme ( branching enzyme ), cuts the chain every 7 to 12 glucose molecules and adds the cut piece "lateral" (alpha -1 ,6 -glycosidic ) to a minimum of 11 molecules long chain.

Glycogen degradation

The linear portion of glycogen is degraded by the enzyme glycogen phosphorylase. This is pyridoxal phosphate - dependent. It catalyzes the phosphate -free bond at the C- atom 1 of glucose. The glycoside bond between the glucose molecules is cleaved, and there is formed glucose-1 -phosphate. This can be transformed by a mutase in glucose-6 -phosphate. Glucose -6-phosphate is the common form of glucose in a cell. Free glucose would arise, should the hexokinase IV, an enzyme that plays a role in glycolysis, produced glucose -6-phosphate using a phosphoryl group from ATP. In addition, an increased concentration of glucose in the cell causes a decrease of the concentration gradient between cytosol and the extracellular space, so that the glucose transport is reduced in the cell.

The glycogen phosphorylase can break down in front of a branch point glycogen only up to the fourth glucose molecule. At this point, the 4- α - glucanotransferase ( an enzymatic activity of debranching enzyme) comes into play: This enzyme transfers three of the four glucose molecules from the branching point to another chain and adds it to linear. The remaining alpha-1 ,6 -glycosidically linked glucose molecules will be cleaved by the enzymatic activity of another debranching enzyme, wherein free glucose is formed. Glycogen breakdown in the thus created to about 90 % of glucose -1-phosphate, as located only every tenth glucose molecule is attached to a branching point in the section.

In volume terms has the largest muscles of glycogen. However, it lacks the enzyme glucose-6 -phosphatase, which is the phosphate moiety at the C- 6 atom of the glucose can be split off. This occurs only in liver cells, kidney cells and enterocytes. Thus, use their glycogen storage effectively to the liver and kidneys, low blood sugar levels ( eg at night) to buffer.

Hormonal Regulation of the assembly and disassembly of glycogen

Both the glycogen as well as the glycogen synthase has two forms: an A and a B-form. The two forms can be converted by phosphorylation by a kinase and dephosphorylation by a phosphatase another. As the a- form in each case has substantially higher activity than the B- form, the speed of the respective reaction can be adapted to the requirements of the metabolism in this manner.

In the case of glycogen phosphorylase is phosphorylated, the a- form. It is phosphorylated by a hormonally regulated phosphorylase kinase and dephosphorylated also a hormonally regulated protein phosphatase. While the b- form is adapted to local needs in liver cells mainly by adenosine monophosphate ( AMP) by allosteric control, the a- form is always active and provides in a short time, large amounts of glucose to peripheral tissues. The conversion of the inactive to the active form by phosphorylation is controlled hormone. The activation of glycogen phosphorylase by the kinase is a typical stress response. The protein phosphatase are activated in an excess supply of glucose to prevent additional release. The most important mechanism of activation of glycogen phosphorylase is via a phosphorylation cascade which is of the second messenger cyclic adenosine monophosphate (cAMP ) is set in motion. Binds a hormone which causes an increase in blood glucose, such as glucagon, or epinephrine, to the corresponding receptors on the membrane of the hepatocytes, as via activation of a trimeric G protein stimulation of the enzyme adenylyl cyclase. This forms the cAMP from ATP. cAMP activates allosterically a specific protein kinase, protein kinase A, which phosphorylates this already called phosphorylase kinase, which then phosphorylates glycogen phosphorylase subsequently and thus converts the b- to the a- form.

The consequence of this cascade activation is a tremendous amplification of the original hormone signal (the present in nanomoles first messengers ) to a metabolic reaction millimolar. cAMP is degraded by a so-called phosphodiesterase again, so that the signal is limited in time.

The processes in the muscle are analogous, but the typical hunger hormone glucagon has no effect there. However, insulin activates protein phosphatase (PP1 ) and the phosphodiesterase ( PDE) and thus acts antagonistically to the stress and hunger signals. Glycogen synthesis is regulated in the opposite direction, i.e., it is inactivated by phosphorylation and is activated by dephosphorylation, wherein in any case some of the same kinases and phosphatases involved in this regulation. The a- form is therefore the dephosphorylated, the b- form phosphorylated. The latter is only active in the presence of high concentrations of glucose -6-phosphate, such as in a large surplus of food glucose in the liver. Accordingly, the hormonal regulation is to be understood, i.e., insulin stimulates epinephrine and glucagon inhibit glycogen synthase.