Glycogen

Glycogen is an intracellular metabolite and important repository of energy central to cellular anabolism and storage on the one hand, and energy-yielding catabolic pathways activated by nutrient crises on the other.

From: Encyclopedia of Cell Biology , 2016

Liver : Non-Neoplastic Diseases

John R. Goldblum MD , in Rosai and Ackerman's Surgical Pathology , 2018

Glycogenic Hepatopathy and Other Features of Diabetes Mellitus in the Liver

As discussed previously, a major cause of hepatomegaly in patients with diabetes is steatosis. In both adults and children with type 1 diabetes mellitus, hepatomegaly and abnormalities of liver enzymes also occur as a consequence of hepatocellular glycogen accumulation. This is believed to be a function of the body habitus and state of insulin resistance rather than glycemic control. The livers of affected patients are characterized by marked glycogenosis, a pathologic overloading of hepatocytes with glycogen, known as glycogenic ordiabetic hepatopathy. 427 Liver biopsy shows diffusely pale staining hepatocytes on H&E stains (Fig. 19.37), with excessive glycogen accumulation demonstrated by PAS stains. Ultrastructural examination reveals marked glycogen accumulation in the cytoplasm and nuclei. 427 If accompanied by cushingoid features, growth retardation, and delayed puberty, a diagnosis of Mauriac syndrome can be made. 459 The distinction between steatosis and glycogenosis is important: whereas steatosis may progress to fibrosis and cirrhosis, glycogenosis does not, but reflects the need for better diabetic control. Glycogenosis and steatosis cannot be distinguished reliably on ultrasound examination; the histology, however, is definitive. 460 Patients undergoing dietary management of urea cycle defects with diets containing essential amino acids may have similar focalor diffuse glycogen accumulation in hepatocytes which—exceptfor the focality in deposition—resembles that in glycogen storage disease. 461 Glycogenosis was also described in a patient withanorexia nervosa where it was interpreted as an adaptive response to starvation. 462

Sinusoidal lesions may also be part of the changes seen in the liver in diabetes. Marked sinusoidal fibrosis has been reported secondary to longstanding diabetes mellitus, in the absence of NASH. The patients have evidence of microvascular complications, including retinopathy, nephropathy, and peripheral and autonomic neuropathy. Liver biopsy shows extensive dense perisinusoidal fibrosis, and immunostaining reveals basement membrane components in a perisinusoidal distribution. The term diabetic hepatosclerosis (DHS) has been suggested for this entity, indicating a form of diabetic microangiopathy affecting the liver. 463 Electron microscopy of sinusoids and sinusoidal cells reveals numerous thick collagen bundles in the space of Disse, and increased basement membrane–like material underlying the sinusoidal cell population. Perisinusoidal cells appear active with abundant rough endoplasmic reticulum and thick cellular processes. 464 The prevalence of DHS was 12% in an autopsy series, suggesting that it is not uncommon, but in the majority of patients it was clinically silent 465 ; another more restricted study of autopsied diabetic patients revealed DHS in only one case out of 57, associated with nodular glomerulosclerosis and hepatic hyaline arteriolosclerosis. 466

GLYCOGEN

M.H.M. Rocha Leão , in Encyclopedia of Food Sciences and Nutrition (Second Edition), 2003

Introduction

Glycogen is a glucose polysaccharide occurring in most mammalian and nonmammalian cells, in microorganisms, and even in some plants. It is an important and quickly mobilized source of stored glucose. In vertebrates it is stored mainly in the liver as a reserve of glucose for other tissues. In hepatocyte cells it is accumulated and mobilized according to blood glucose availability and to extrahepatic cells. Glycogen is also stored in muscles and fat cells. In the muscle it seems to be mainly used for energy purposes as metabolic fuel for glucolysis producing glucose 6-phosphate. Thus, glycogen plays a crucial role as a systemic and cellular energy source and also as an energy store. A great number of enzymes and hormones control the synthesis and degradation of glycogen. Consequently, stores of human body glycogen may vary dramatically due to diet, exercise, and stress.

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B012227055X005630

Liver Physiology and Energy Metabolism

Mark Feldman MD , in Sleisenger and Fordtran's Gastrointestinal and Liver Disease , 2021

Glycogen Formation

Glycogen stored in the liver is the main source of rapidly available glucose for the glucose-dependent tissues, such as RBCs, retina, renal medulla, and brain. 109 Hepatic glycogen stores contain up to a 2-day supply of glucose before gluconeogenesis occurs, mainly from lactate, a 3-carbon end-product of anaerobic glucose metabolism. 93, 110 Hepatic gluconeogenesis produces up to 240 mg of glucose a day, which is approximately twice the metabolic need of the RBCs, retina, and brain. The 3-carbon precursors generated by anaerobic metabolism from muscle, intestine, liver, or RBCs may account for up to 50% of the glycogen pool formed during nonabsorptive states. Alanine, another major glucose precursor, is generated by the catabolism of muscle proteins, which is a major cause of muscle wasting during prolonged fasting. Glycogen stored in muscle is used locally and cannot be exported out of the cell because muscles lack glu-6-Pase. The relative contribution of each of the precursors to glycogen synthesis depends on the nutritional status, amount, and route of glucose administration (oral vs. IV) and on hormonal regulation.

Rapid switching between glycogen synthesis and breakdown is mediated by a cascade of enzymes that are regulated by local nutrients and hormones. 93 Glycogen phosphorylase, which is activated by phosphorylation, catalyzes the breakdown of glycogen subunits, and glycogen synthase, which is activated by dephosphorylation, catalyzes the addition of UDP-glucose to the expanding glycogen chain. In addition, glucose and glucose-6-P are allosteric activators of the synthase enzyme, whereas glucose binding inactivates the phosphorylase.

Glycogen exists as 2 distinct populations consisting of proglycogen, with a molecular weight of approximately 4 × 105, and macroglycogen, with a molecular weight of 1 × 107, the concentrations of which depend on the relative activities of enzymes favoring proglycogen formation (phosphorylase and debranching enzymes) and those favoring glycogenin formation (branching enzymes). The ability of glycogenin to initiate the formation of glycogen is important in hepatic carbohydrate metabolism. The existence of these 2 distinct pools of glycogen permits subtle control of glucose levels, and their relative contributions could have a physiologic role in disease states such as diabetes mellitus.

Glycogen

Larry R. Engelking , in Textbook of Veterinary Physiological Chemistry (Third Edition), 2015

Glycogenesis

The structure of glycogen is represented in Fig. 23-1 . Branching of the glycogen molecule occurs at an average frequency of every ten glucose residues. Branching increases its solubility as well as the rate at which glucose can be stored and retrieved. Each glycogen molecule has a protein, glycogenin, covalently linked to the polysaccharide. Linear glycogen chains consist of glucose molecules linked together by α-1,4 glycosidic bonds. At each of the branch points, two glucose molecules are linked together by α-1,6 glycosidic bonds. The non-reducing ends of the glycogen molecule are the sites where both synthesis and degradation occur.

Figure 23-1.

The pathway by which glucose-6-phosphate (Glc-6-P) is converted to glycogen is shown in Fig. 23-2 . Following glucose phosphorylation by hexokinase (HK) or glucokinase, Glc-6-P may be converted to glucose-1-phosphate (Glc-1-P) by the reversible enzyme, phosphoglucomutase (PGM). This reaction, like that for the phosphorylation of glucose, requires Mg++ as a cofactor. Glc-1-P is next converted to the active nucleotide, uridine diphosphate-glucose (UDP-Glc, Fig. 23-3 ), by the action of UDPGlc pyrophosphorylase. UDP-glucose now becomes a branch point for entry into the hepatic uronic acid pathway (via UDP-glucuronate, see Chapter 29), lactose synthesis in the mammary gland (via UDP-galactose), or glycogen synthesis in several tissues (via enhanced activity of glycogen synthase).

Figure 23-2.

Figure 23-3.

Glycogen synthase catalyzes the rate-limiting step in glycogenesis. Being a key enzyme, its activity can be inhibited by phosphorylation, or activated by dephosphorylation (see Chapter 58). Postprandial (i.e., after a meal) conditions activate glycogen synthase activity in various ways. The parasympathetic nervous system (PNS) has an indirect effect via autonomic stimulation of insulin release from the pancreas. High levels of glucose also stimulate insulin release. Insulin, the anabolic hormone that promotes storage of dietary bounty, stimulates activity of protein phosphatase 1, which in turn stimulates glycogen synthase activity by causing its dephosphorylation.

When the α-1,4 chain of glycogen extends to 11-15 glucose residues from the nearest branch point, branching occurs. A block of 6-7 glucose residues is moved from the end of one chain to another chain, or to an internal position of the same chain. By catalyzing these α-1,4 → α-1,6 glucan transfers, the non-regulatory branching enzyme helps to create new sites for elongation by glycogen synthase.

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780123919090500232

Cerebral Blood Flow and Metabolism and Cerebral Ischemia

H. Richard Winn MD , in Youmans and Winn Neurological Surgery , 2017

Storage as Glycogen

The brain converts a limited amount of glucose into glycogen to form its principal energy reserve. Although there is typically 3 to 4 times more glycogen than free glucose in the brain, it still amounts to no more than approximately 4 µmol/g, and were it to serve as the sole fuel source, it would be consumed completely in a few minutes. Instead, more contemporary evidence suggests that it exists as a metabolic buffer system and is metabolized slowly, so complete turnover of brain glycogen stores normally takes 3 to 5 days. 46

Glycogenesis requires the action of glycogen synthase on glucose subunits that have first undergone phosphorylation by ATP. Although both astrocytes and neurons possess the necessary enzymes, synthesis of glycogen is normally confined to astrocytes. Storage of glycogen is also almost exclusive to astrocytes and serves to augment neuronal energy requirements during periods of intense activity and pathologic shortages of glucose. Glycogen undergoes glycogenolysis by the enzyme glycogen phosphorylase to form lactate under stimulation by neurotransmitters such as norepinephrine, vasoactive intestinal polypeptide, histamine, serotonin, and certain metabolic by-products of neuronal activity, such as K+ and adenosine. 47

It has been hypothesized that this lactate is transferred from astrocytes to neurons for use as an energy substrate, which is discussed further in the next section. 48 In contrast to the metabolism of glucose, release of glucose equivalents from glycogen does not require prior "priming" with ATP.

Glycogen

Gerhard Pfleiderer , in Methods of Enzymatic Analysis, 1965

Publisher Summary

This chapter elaborates the methods for the enzymatic determination of glycogen as D-glucose using hexokinase, pyruvic kinase, and lactic dehydrogenase. Glycogen is usually determined by hydrolysis to glucose, which is then estimated chemically. A new departure is the enzymatic determination of the glucose liberated. In principle, all methods for the enzymatic determination of glucose should be applicable; however, the method described in this chapter has already proved itself. Interference occurs in the enzymatic determination of D-(+)-glucose with hexokinase and glucose-6-phosphate dehydrogenase, if the glucose-6-phosphate dehydrogenase preparation contains 6-phosphogluconic dehydrogenase; pure preparations are difficult to prepare and therefore, commercial preparations are expensive. In the three reactions discussed in the chapter, glucose is phosphorylated with ATP and stoichiometric amounts of ADP are formed. The ADP is converted with PEP in the auxiliary reaction (second reaction) to ATP and pyruvate, the latter being determined by means of the decrease in optical density on oxidation of DPNH to DPN (indicator reaction 3). Owing to the favorable Michaelis and equilibrium constants, all the reactions proceed quantitatively from left to right.

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780123956309500128

Metabolic Pathways in the Human Body

Tsugikazu Komoda , Toshiyuki Matsunaga , in Biochemistry for Medical Professionals, 2015

Glycogen Synthesis

Glycogen is the reserve polysaccharide in the body and is mainly comprised of hepatic glycogen. Glycogen is synthesized in the liver and muscles. α-D-Glucose combines to form glycogen continuously. There is a reduced sugar that indicates reduction characteristics, and many non-reducing residues that do not indicate reduction in the glycogen molecule. When glucose binds to glycogen, or when it is cleaved, a non-reducing residue is involved. The production of glycogen from glucose is shown in Figure 4.4. An important enzyme in glycogen synthesis is glycogen synthase. By the action of this enzyme, one glucose can combine with glycogen. However, when glucose binds to glycogen, it links with a non-reducing residue.

Figure 4.4. Glycogen shunt and activation of phosphorylase by cyclic adenosine monophosphate (cAMP).

 Source: Modified from Fig. II-15A in Kagawa and Nozawa, Illustrated Medical Chemistry (2001, p. 132).

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780128019184000049

Carbohydrates, Nucleosides & Nucleic Acids

Jack Preiss , in Comprehensive Natural Products II, 2010

6.15.2.1 Bacterial Glycogen

Glycogen occurs in many bacteria, and accumulates under environmental conditions where growth is limited and there is an excess carbon supply. 7,8,10,11,24–26 Glycogen accumulation has been shown to occur in the stationary phase of the growth cycle due to limitations in the source of sulfur, nitrogen, or phosphate. Glycogen is not required for bacterial growth, and mutants deficient in glycogen may grow as well as their wild-type strains. Biological functions of bacterial glycogen have been reviewed 25 and under conditions of no available carbon source, glycogen is probably utilized to preserve cell integrity. Bacteria require energy for maintenance under nongrowing conditions and this 'energy of maintenance' is the energy needed for processes such as maintenance of motility and intracellular pH, chemotactic response, turnover of proteins and RNA, and osmotic regulation. In media devoid of carbon source, Escherichia coli and Enterobacter aerogenes having glycogen do not degrade their RNA and protein components. In contrast, the glycogen-deficient bacteria release NH3 from their nitrogen-containing components. 26 Glycogen-containing E. aerogenes, E. coli, and Streptococcus mitis also survive better than these organisms with no glycogen. Another function for glycogen is suggested for various Clostridia species. Clostridia can accumulate glycogen up to 60% of their dry weight and prior to spore formation, the glycogen is rapidly degraded. 27 Clostridial glycogen-deficient strains are poor spore formers, suggesting that glycogen serves as a source of carbon and energy for spore formation and maturation. Although these studies suggest that glycogen plays a role in bacterial survival, glycogen-rich Sarcina lutea cells die faster when starved in phosphate buffer than cells with no polysaccharide. 28

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780080453828006444

Carbohydrates and Their Derivatives Including Tannins, Cellulose, and Related Lignings

Jack Preiss , Mirta Sivak , in Comprehensive Natural Products Chemistry, 1999

3.14.2.1 Glycogen in Bacteria

Glycogen is found in many bacteria, and usually accumulates in environmental conditions that limit growth and also offer excess carbon supply. 7,23–25 Glycogen accumulation has been shown to occur in the stationary phase of the growth cycle as a response to limitations in the supply of nitrogen, sulfur, or phosphate. Glycogen is not required for bacterial growth, and glycogen-deficient mutants grow as well as the wild-type strains. The biological functions of bacterial glycogen have been reviewed; 25 under nonfavorable conditions and when an alternative carbon source is not available, glycogen is probably utilized to preserve cell integrity. Bacteria require energy for maintenance under nongrowing conditions and this is defined as "energy of maintenance," the energy required for processes such as maintenance of motility and intracellular pH, chemotactic response, turnover of proteins and RNA, and osmotic regulation. In media lacking a carbon source, Escherichia coli and Enterobacter aerogenes containing glycogen do not degrade their RNA and protein components, while the glycogen-deficient bacteria release NH3 for their nitrogen-containing components. 25 Glycogen-containing E. aerogenes, E. coli, and Streptococcus mitis also survive better than organisms having no glycogen. Another function for glycogen has been suggested in various Clostridia species; these organisms accumulate glycogen up to 60% of their dry weight before or during initiation of sporulation and, during spore formation, this glycogen is rapidly degraded. 26 Glycogen-deficient strains are poor spore formers, suggesting that glycogen serves as a source of carbon and energy for spore formation and maturation. Although these studies suggest that glycogen plays a role in bacterial survival, glycogen-rich Sarcina lutea cells die faster when starved in phosphate buffer than cells with no polysaccharide. 27

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780080912837000825

Glial Glycogen Metabolism☆

I. Allaman , P.J. Magistretti , in Reference Module in Biomedical Sciences, 2015

Concluding Remarks

Glycogen represents the major energy store of the brain. During decades of research, glycogen has been perceived as an emergency reserve used in case of energy supply deficiency, but more recent data, obtained with the development of new techniques, now points to a physiological role for glycogen in relation to neuronal activation. Nevertheless, some questions as to glycogen physiological processes still need further exploration. In this context, the advent of noninvasive NMR spectroscopic methods may allow the development of very useful experimental approaches to investigate glycogen function in humans. The quite exclusive localization of glycogen in glia, and its mobilization upon neuronal activation, underline the tight metabolic cooperation occurring between neurons and astrocytes.

Read full chapter

URL:

https://www.sciencedirect.com/science/article/pii/B9780128012383046213