Glycogen, Starch and Sucrose Synthesis


Glucose constitutes a universal energy‐providing molecule. It is the primary fuel substance for a wide array of organisms from bacteria to man. Its great utility as an energy source is that it can be oxidised for the production of the high energy molecule, adenosine triphosphate (ATP), even in the absence of oxygen. Within humans, certain tissues, in particular red blood cells, derive all of their energy from the anaerobic oxidation of glucose. The human brain prefers glucose for energy and consumes the largest percentage of glucose on a daily basis. For these reasons the consumption of glucose or glucose containing sugars, such as sucrose, is important for life processes. Given the importance of glucose, it is not surprising that organisms store this carbohydrate for easy access for ATP production. Storage of glucose is in the form of a polymer composed of long linear chains and occasional branched chains termed glycogen in animals and starch in plants. Due to its highly important role in cellular viability, glucose storage and utilisation in humans is stringently controlled by hormones and neurotransmitters.

Key Concepts:

  • Glucose represents a key energy molecule for the majority of phyla.

  • Glucose uptake from dietary sources (e.g. starch and sucrose) involves both sodium‐dependent and ‐independent intestinal enterocyte membrane transporters.

  • Ready access to glucose is ensured via its storage as a highly polymeric molecule in plants and animals.

  • Storage and release of glucose, from cellular stores such as glycogen, is highly regulated by hormones and neurotransmitters.

  • Key hormones in the overall regulation of glycogen homeostasis include insulin, glucagon, and epinephrine.

  • Abnormalities in the genes encoding the enzymes that regulate glucose storage and release in humans result in a family of disorders called glycogen storage diseases.

Keywords: carbohydrates; glucose; glycogenolysis; glucagon; insulin; epinephrine

Figure 1.

Haworth‐style projection of the structure of α‐d‐glucose.

Figure 2.

Structure of sucrose.

Figure 3.

Structure of glycogen. Blue, red and orange circles represent glucose monomers. Blue are attached vis α(1,4)‐glycosidic bonds and red are via α(1,6)‐glycosidic bonds. Orange circles represent the reducing ends of the glycogen polymer.

Figure 4.

The role of glycogenin in glycogen synthesis. Glycogenin is a protein that constitutes the nucleation centre for the de novo formation of glycogen. The protein possesses self‐glucosylating activity that attaches 6–8 glucose residues in α(1,4)‐linkage to the hydroxyl group of a tyrosine (Tyr) residue in the protein. Following attachment of the glucose residues the complex becomes a substrate for further addition of glucose residues via the actions of glycogen synthase and glycogen branching enzyme.

Figure 5.

Mode of action of PKA activation. In this example, glucagon binds to its cell‐surface receptor, thereby activating the receptor. Activation of the receptor is coupled to the activation of a receptor‐coupled G‐protein (GTP‐binding and hydrolysing protein) composed of 3 subunits (α, β and γ). Upon activation the alpha subunit dissociates and binds to and activates adenylate cyclase. This type of G‐protein is, therefore, referred to as Gs. Adenylate cyclase then converts ATP to cyclic AMP (cAMP). The cAMP thus produced then binds to the regulatory subunits of PKA leading to dissociation of the associated catalytic subunits. The catalytic subunits are inactive until dissociated from the regulatory subunits. Once released, the catalytic subunits of PKA phosphorylate numerous substrates using ATP as the phosphate donor.

Figure 6.

Regulation of glycogen synthase by phosphorylation and dephosphorylation. PKA is cAMP‐dependent protein kinase. PPI‐1 is phosphoprotein phosphatase‐1 inhibitor. Whether a factor has positive or negative effects on any enzyme is indicated with green arrows (positive) or red T‐lines (negative). Briefly, glycogen synthase a is phosphorylated, and rendered much less active and requires glucose‐6‐phosphate to have any activity at all. Phosphorylation of glycogen synthase is accomplished by several different enzymes. The most important is synthase‐phosphorylase kinase (GS/GP kinase), the same enzyme responsible for phosphorylation (and activation) of glycogen phosphorylase. PKA (itself activated through receptor‐mediated mechanisms) also phosphorylates glycogen synthase directly. The effects of PKA on PPI‐1 are the same as those described above for the regulation of glycogen phosphorylase. The other enzymes shown to directly phosphorylate glycogen synthase are protein kinase C (PKC), calmodulin‐dependent protein kinase, glycogen synthase kinase‐3 (GSK‐3) and two forms of casein kinase (CK‐I and CK‐II). The enzyme PKC is activated by Ca2+ ions and phospholipids, primarily diacylglycerol, DAG. DAG is formed by receptor‐mediated hydrolysis of membrane phosphatidylinositol bisphosphate (PIP2).

Figure 7.

Pathways involved in the regulation of glycogen synthase by epinephrine activation of α1‐adrenergic receptors. PKC is protein kinase C. PLC‐β is phospholipase C‐β. The substrate for PLC‐β is phosphatidylinositol‐4,5‐bisphosphate (PIP2) and the products are IP3, inositol‐1,4,5‐trisphosphate and DAG, diacylglycerol. The abbreviations (+ve) and (−ve) refer to positive and negative effects, respectively.

Figure 8.

Reaction catalysed by glycogen phosphorylase.

Figure 9.

Regulation of glycogen phosphorylase activity. PKA is cAMP‐dependent protein kinase. PPI‐1 is phosphoprotein phosphatase‐1 inhibitor. Whether a factor has positive or negative effects on any enzyme is indicated with green arrows (positive) or red T‐lines (negative). Briefly, phosphorylase‐b is phosphorylated, and rendered highly active, by glycogen synthase‐phosphorylase kinase (GS/GP kinase for short in this figure). Phosphorylase kinase is itself phosphorylated, leading to increased activity, by PKA (itself activated through receptor‐mediated mechanisms). PKA also phosphorylates PPI‐1 leading to an inhibition of phosphate removal allowing the activated enzymes to remain so longer. Calcium ions can activate phosphorylase kinase even in the absence of the enzyme being phosphorylated. This allows neuromuscular stimulation by acetylcholine, which results in increased intracellular free Ca2+, to lead to increased glycogenolysis in the absence of receptor‐mediated stimulation of PKA activity.

Figure 10.

Epinephrine regulation of glycogen phosphorylase through activation of α1‐adrenergic receptors. PLC‐β is phospholipase C‐β. The substrate for PLC‐β is phosphatidylinositol‐4,5‐bisphosphate (PIP2) and the products are IP3, inositol trisphosphate and DAG, diacylglycerol. The abbreviations (+ve) and (−ve) refer to positive and negative effects, respectively.



Browner MF and Fletterick RJ (1992) Phosphorylase: a biological transducer. Trends in Biochemical Sciences 17: 66–71.

Johnson LN (1992) Glycogen phosphorylase: control by phosphorylation and allosteric effectors. FASEB Journal 6: 2274–2282.

Larner J (1990) Insulin and the stimulation of glycogen synthesis. The road from glycogen structure to glycogen synthase to cyclic AMP‐dependent protein kinase to insulin mediators. Advances in Enzymology and Related Areas of Molecular Biology 63: 173–231.

Maroto R, Calvo S, Sancho C and Esquerro E (1992) Alpha‐ and beta‐adrenoceptor cross‐talk in the regulation of glycogenolysis in dog and guinea‐pig liver. Archives Internationales de Pharmacodynamie et de Therapie 317: 35–46.

Meinke MH and Edstrom RD (1991) Muscle glycogenolysis. Regulation of the cyclic interconversion of phosphorylase a and phosphorylase b. Journal of Biological Chemistry 266(4): 2259–2266.

Nakielny S, Campbell DG and Cohen P (1991) The molecular mechanism by which adrenalin inhibits glycogen synthesis. European Journal of Biochemistry 199: 713–722.

Nuttall FQ and Gannon MC (1993) Allosteric regulation of glycogen synthase in liver. A physiological dilemma. Journal of Biological Chemistry 268(18): 13286–13290.

Ren JM and Hultman E (1990) Regulation of phosphorylase a activity in human skeletal muscle. Journal of Applied Physiology 69(3): 919–923.

Vardanis A and Hudson AJ (1991) Regulation of glycogen synthesis in human skeletal muscle: does cellular glycogen control glycogen synthase phosphatase activity? Biochemistry International 25(2): 289–298.

Wolosiuk RA and Pontis HG (1974) Studies on sucrose synthetase. Kinetic mechanism. Archives of Biochemistry and Biophysics 165(1): 140–145.

Zieve FJ and Glinsmann WH (1973) Activation of glycogen synthetase and inactivation of phosphorylase kinase by the same phosphoprotein phosphatase. Biochemical and Biophysical Research Communications 50(3): 872–878.

Further Reading

Lomako J, Lomako WM and Whelan WJ (1988) A self‐glucosylating protein is the primer for rabbit muscle glycogen biosynthesis. FASEB Journal 2: 3097–3103.

Pitcher J, Smythe C and Cohen P (1988) Glycogenin is the priming glucosyltransferase required for the initiation of glycogen biogenesis in rabbit skeletal muscle. European Journal of Biochemistry 176(2): 391–395.

Smythe C and Cohen P (1991) The discovery of glycogenin and the priming mechanism for glycogen biosynthesis. European Journal of Biochemistry 200: 625–631.

Web Link

The Medical Biochemistry Page.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
King, Michael W(Nov 2014) Glycogen, Starch and Sucrose Synthesis. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001368.pub2]