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.
