Harpers

152 / CHAPTER 18Table 18–2. Glycogen storage diseases.Glycogenosis Name Cause of Disorder CharacteristicsType I Von Gierke’s disease Deficiency of glucose-6-phosphatase Liver cells and renal tubule cells loadedwith glycogen. Hypoglycemia, lacticacidemia,ketosis, hyperlipemia.Type II Pompe’s disease Deficiency of lysosomal α-1→4- and Fatal, accumulation of glycogen in lyso-1→6-glucosidase (acid maltase) somes, heart failure.Type III Limit dextrinosis, Forbes’ or Absence of debranching enzyme Accumulation of a characteristicCori’s diseasebranched polysaccharide.Type IV Amylopectinosis, Andersen’s Absence of branching enzyme Accumulation of a polysaccharide havdiseaseing few branch points. Death due tocardiac or liver failure in first year of life.Type V Myophosphorylase deficiency, Absence of muscle phosphorylase Diminished exercise tolerance; musclesMcArdle’s syndromehave abnormally high glycogen content(2.5–4.1%). Little or no lactate inblood after exercise.Type VI Hers’ disease Deficiency of liver phosphorylase High glycogen content in liver, tendencytoward hypoglycemia.Type VII Tarui’s disease Deficiency of phosphofructokinase As for type V but also possibility of heinmuscle and erythrocytesmolytic anemia.Type VIII Deficiency of liver phosphorylase As for type VI.kinaseported. Some of the conditions described have benefitedfrom liver transplantation.SUMMARY• Glycogen represents the principal storage form ofcarbohydrate in the mammalian body, mainly in theliver and muscle.• In the liver, its major function is to provide glucosefor extrahepatic tissues. In muscle, it serves mainly asa ready source of metabolic fuel for use in muscle.• Glycogen is synthesized from glucose by the pathwayof glycogenesis. It is broken down by a separate pathwayknown as glycogenolysis. Glycogenolysis leads toglucose formation in liver and lactate formation inmuscle owing to the respective presence or absence ofglucose-6-phosphatase.• Cyclic AMP integrates the regulation of glycogenolysisand glycogenesis by promoting the simultaneousactivation of phosphorylase and inhibition of glycogensynthase. Insulin acts reciprocally by inhibitingglycogenolysis and stimulating glycogenesis.• Inherited deficiencies in specific enzymes of glycogenmetabolism in both liver and muscle are the causes ofglycogen storage diseases.REFERENCESBollen M, Keppens S, Stalmans W: Specific features of glycogenmetabolism in the liver. Biochem J 1998;336:19.Cohen P: The role of protein phosphorylation in the hormonalcontrol of enzyme activity. Eur J Biochem 1985;151:439.Ercan N, Gannon MC, Nuttall FQ: Incorporation of glycogenininto a hepatic proteoglycogen after oral glucose administration.J Biol Chem 1994;269:22328.Geddes R: Glycogen: a metabolic viewpoint. Bioscience Rep1986;6:415.McGarry JD et al: From dietary glucose to liver glycogen: the fullcircle round. Annu Rev Nutr 1987;7:51.Meléndez-Hevia E, Waddell TG, Shelton ED: Optimization ofmolecular design in the evolution of metabolism: the glycogenmolecule. Biochem J 1993;295:477.Raz I, Katz A, Spencer MK: Epinephrine inhibits insulin-mediatedglycogenesis but enhances glycolysis in human skeletal muscle.Am J Physiol 1991;260:E430.Scriver CR et al (editors): The Metabolic and Molecular Bases of InheritedDisease, 8th ed. McGraw-Hill, 2001.Shulman GI, Landau BR: Pathways of glycogen repletion. PhysiolRev 1992;72:1019.Villar-Palasi C: On the mechanism of inactivation of muscle glycogenphosphorylase by insulin. Biochim Biophys Acta 1994;1224:384.