Introduction:
An essential factor of maintaining the level of glucose in body is the metabolism of glycogen. Insulin, glucagon, and epinephrine, as well as a number of allosteric factors, regulate the production and breakdown of glycogen in a universal way.
Glycogenesis is an anabolic biochemical reaction which involved the synthesis of glycogen. Basically, glucose molecules are added to the chains of glycogen which takes place when blood glucose levels are sufficiently high to allow excess glucose to be stored in liver and muscle cells. Although it occurs in all human tissues, it is most prevalent in the muscles and liver. The central nervous system has relatively little capacity for glycogen production or storage, therefore it is entirely reliant on blood glucose for energy.
Location:
Although glucose is converted into glycogen in numerous tissues, the liver and muscle are especially remarkable because of their higher levels of glycogen synthesis and physiological relevance.
Glycogen makes up around 8% of the weight of the liver in humans, especially after consuming a lot of carbohydrates. Especially after a long fasting, this amount is significantly decreased. Glycogen makes up about 1% of the weight of skeletal muscle.
It occurs in the cytoplasm of the cells in the liver, fat tissue, and muscle.
Requirements:
- UDP-glucose formation by UDP-glucose pyrophosphorylase
- Glycogen synthesis by glycogen synthase
- Glycogen Branching enzyme
Steps:
The hormone insulin stimulates glycogenesis.
However, insulin has a significant impact on the liver cells’ ability to metabolize glucose, promoting glycogenesis and inhibiting glycogenolysis (breaking down of glycogen).
Formation of a sugar nucleotide (UDP-Sugar)
It consists of the following steps:
- Glucose phosphorylation
- Formation of Glucose-1-phosphate
- Glucose activation
Sugar nucleotides are the substrates for polymerization of monosaccharides into disaccharides, glycogen, starch, cellulose, and more complex extracellular polysaccharides. The role of sugar nucleotides in the biosynthesis of glycogen and many other carbohydrate derivatives were first discovered by the Argentine biochemist Luis Leloir.
Fig: Synthesis of sugar nucleotide
The enzymes hexokinase (in muscle) and glucokinase (in liver) convert glucose to glucose
6-phosphate. Phosphoglucomutase catalyses the conversion of glucose 6-phosphate to glucose 1-phosphate. Uridine diphosphate glucose (UDPG) is synthesized from glucose 1-phosphate and UTP by UDP-glucose pyrophosphorylase.
A sugar phosphate and nucleoside triphosphate (NTP) combine through a condensation process.
Initiation of glycogenesis
In the reaction catalysed by glycogen synthase, UDP-glucose serves as the immediate donor of glucose residues and encourages the transfer of the glucose residue from UDP-glucose to a nonreducing end of a branching glycogen molecule.
Initiation of new glycogen chain required a small fragment of pre-existing glycogen that act as a ‘primer’. The formation of 1,4-glycosidic bonds is carried out by glycogen synthase that forms form α-1,4 linkages by moving the glucose from UDP-glucose to the non-reducing end of glycogen.
Fig: Synthesis of glycogen
Branch synthesis in glycogen
Glycogen synthase catalyses only α- 1–4 glycosidic bonds that results in to the formation of
α- amylose. The glycogen-branching enzyme (amylo (1–4→1–6) transglycosylase) is responsible for forming a new branch point during glycogen synthesis. The branching enzyme cleaves 1-4 bonds after a number of glucose units have been connected in a straight chain.
It transfers to a C-6 hydroxyl group of a glucosyl residue that is four residues away from an existing branch after breaking a 7-unit segment of 1-4 residues from a glycogen chain. Reattachment is accomplished by forming a,1-6 connection.
Fig: Branch synthesis in glycogen
Significances:
Food is the source of glucose and its precursors. However, they might not be a dependable and consistent source of energy under some circumstances.
By maintaining blood glucose levels regular and supplying energy for muscle contraction, glycogen, the main type of glucose storage and the main source of non-oxidative glucose for skeletal muscle and the liver, makes significant contributions.
Therefore, the glycogenesis process is an inherent mechanism of the body that stores the extra carbohydrates as glycogen, which can be converted to glucose when necessary.
Regulations:
In order to control blood sugar levels, glycogen synthesis is strictly regulated. When well-fed, it is stimulated, and when fasting, it is inhibited. Glycogen synthesis is influenced by a number of parameters, which are based on the regulation of metabolic activity.
Availability of substrate
When blood glucose levels are high in a fed condition, glucose 6 phosphate, the substrate for UDP glucose, is likewise elevated. This allosterically boosts glycogenesis. Additionally, because there is a lack of substrate and a requirement for glucose during a fast, the breakdown of glycogen—the reverse of glycogenesis—occurs.
Hormone
Glycogen synthase, the key enzyme of glycogenesis exists in inactive (phosphorylated) and activate (dephosphorylated) form.
Glucagon and epinephrine are diabetogenic hormones that raise blood glucose levels. Thus, they prevent the production of glycogen, which lowers blood sugar levels and allows it to be stored for later use.
On the other hand, a hormone that prevents diabetes is insulin. It encouraging the uptake of glucose by muscle cells and the production of glycogen in the liver and muscle decreasing blood sugar levels.
Clinical aspect:
In the liver, glucose that is not used right away is transformed and stored as glycogen. Glycogenolysis is used to release these reserves as required. Both processes result in glycogenosis, which is caused by an enzyme deficiency.
Hepatomegaly develops when these glycogen reserves are not mobilized. Liver glycogen storage disorders are phenotypes caused by enzyme shortages.
A hereditary illness known as glycogen storage disease (GSD) causes the body to have an enzyme dysfunction that prevents it from properly storing or breaking down the complex sugar glycogen. The liver, muscles, and other parts of the body are all impacted by GSD. There are different variations of GSD.
References:
- Roach, P. J., Skurat, A. V., Harris, R. (2001) Regulation of glycogen metabolism. In The Endocrine Pancreas and Regulation of Metabolism, Cherrington AD and Jefferson LS (eds), Vol. 2, pp. 609–647. New York, NY: Oxford University Press.
- Blanco, A. and Blanco, G., 2017. Medical biochemistry. Academic Press.
- Berg, et al., (2012). Biochemistry (7th, International ed.). Freeman, W.H. p. 650.
- David, L., Nelson, D.L., Cox, M.M., Stiedemann, L., McGlynn Jr, M.E. and Fay, M.R., 2000. Lehninger principles of biochemistry.
- Satyanarayana, U., 2021. Biochemistry, 6e-E-book. Elsevier Health Sciences.