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Gluconeogenesis Steps with Structures

    In this gluconeogenesis steps with structures post we have briefly explained about history, location, gluconeogenesis pathway steps, and regulation process of gluconeogenesis pathway.

    Glycogenesis, Glycogen is the major storage form of carbohydrates in animals, present in all cells, but found mostly in liver and muscle, where it occurs as cytoplasmic granules. It is a highly branched form of amylopectin, with branch points occurring every 8 to 14 glucose residues. Glycogen’s highly branched structure, which has many non-reducing ends, permits the rapid mobilization of glucose in times of metabolic need.

    Location

    Gluconeogenesis pathway takes place in the cytoplasm of cells in muscle, liver, and adipose tissue. Substrate is UDP-glucose and Changes glucose to glycogen.

    Glycogenesis

    The biosynthesis of glycogen from glucose is called gluconeogenesis pathway. Gluconeogenesis pathway takes place when blood glucose levels are sufficiently high to allow excess glucose to be stored. Gluconeogenesis pathway is stimulated by the hormone insulin. Insulin facilitates the uptake of glucose into muscle cells, though it is not required for the transport of glucose into liver cells.

    However, insulin has profound effects on glucose metabolism in liver cells, stimulating gluconeogenesis pathway and inhibiting glycogenolysis, the breakdown of glycogen into glucose. The pathway of glycogenesis includes a series of steps that result in complex glycogen formation in the cytoplasm of the liver and cells of the muscles. The steps of glycogenesis are as follows:

    Gluconeogenesis Pathway

    Glycogenesis

    Step 1

    Glucose phosphorylation – In the initial phase, glucose is phosphorylated into glucose-6-phosphate, a usual reaction in glycolysis. It is catalysed by glucokinase (liver) and hexokinase (muscle).

    Step 2

    Conversion of Glucose-6-Phosphate to Glucose-1-Phosphate – An enzyme Phosphoglucomutase will catalyse the conversion of glucose-6-P is to glucose1-phosphate.

    Step 3

    UTP (uridine triphosphate) attaches to Glucose-1-phosphate in the third step. This step focuses on the reaction of glucose-1-phosphate to UTP thereby forming active nucleotide UDP-Glucose (Uridine diphosphate glucose). The one responsible for such reaction is the enzyme UDP Glucose pyrophosphorylase.

    Step 4

    UDP-Glucose attaches to glycogen primer, a small fragment of already existing glycogen that serves as a primer, in order to stimulate the synthesis of glycogen. The glucose from UDP-Glucose will be accepted by glycogenin. The initial glucose unit is attached to the hydroxyl group of tyrosine of glycogenin. The first molecule of glucose is transferred to glycogenin, which will then take up for glucose residues forming a fragment of primer. It will be the one to accept all glucose molecules.

    Step 5

    Glycogen synthase transfers glucose from UDP-Glucose to glycogen (nonreducing end) forming alpha 1,4-linkages. The same enzyme catalyses the synthesis of the unbranched molecule with alpha-1,4-glycosidic linkages.

    Step 6

    The formation of glycogen branches; The final step is the formation of glycogen branches caused by the effect of branching enzyme, which transfers a small fragment of about five to eight residues of glucose from the non-reducing end of the glycogen chain to another glucose residue linked by alpha-1,6 bond. This action causes the formation of a new non-reducing end. The final result is the elongation and branching out of the glycogen chain.

    Gluconeogenesis Pathway Regulation

    The formation of glycogen primarily depends on the level of glucose in the blood as well as the level of glycogen in the liver and muscle tissues. The activities of hormones in the body also affect the level and release of glycogen. These enzymes include the following:

    Adrenaline

    Adrenaline is produced in the medulla in the adrenal glands as well as some of the central nervous system’s neurons. Adrenaline inhibits glycogen synthase and the activation of glycogen phosphorylase.

    Insulin

    Its effect is opposite to that of adrenaline. Insulin binds to protein primmer and will be converted to a non-phosphorylated form with the aid of glycogen synthase. As a result, the blood sugar level is decreased even after consuming carbohydrate-rich foods. If the body is not effectively producing insulin, a patient suffers from a medical condition called diabetes.

    Calcium ions

    Calcium ions activates glycogen phosphorylase and at the same time inhibit glycogen synthase during gluconeogenesis pathway.

    Further Readings

    Reference

    1. https://www.sciencedirect.com/topics/neuroscience/glycogenesis
    2. https://www.ncbi.nlm.nih.gov/books/NBK549820/
    3. https://www.ncbi.nlm.nih.gov/books/NBK21190/