Disorders of glycogen metabolism Glycogen storage disease By : Dr. hassan el-banna

1. Disorders of glycogen metabolism Glycogen storage disease By : Dr. hassan el-banna

2. GSD (Glycogenosis ) These are a group of genetic diseases that result from a defect in an enzyme required for either glycogen synthesis or degradation, with the formation of abnormal glycogen structure or excessive accumulation of normal glycogen in specific tissues. The defect may be generalized affecting muscles, kidney,intestine &myocardium.

3. Type I: Glycogen storage disease(GSD type I)

6. Type II: glycogen storage disease(GSD type II) Synonymes: Pompe�s disease; lysosomal storage disorders Causes: alpha-1,4-glycosidase deficiency. All organs are affected with massive increase of normal glycogen. Clinical features: Cardio-respiratory failure causes death before age 2.

7. Type III glycogen storage diseaseGSD type III Synonyms: Cori Disease; Forbes Disease Dextrinosis Amylo-1,6 Glycosidase deficiency (Debranching Deficiency). Cause: the enzyme deficiency causes the liver &muscles that form glycogen molecules have an abnormal structure(increased amount with short outer branches). This abnormal structure also prevents the glycogen from being broken down into free glucose.

11. Type V Glycogen Storage Disease(GSD type V) Synonyms: Muscle Phosphorylase Deficiency, McArdle�s Disease . Cause: The phosphorylase enzyme plays a vital role in the breakdown of glycogen into glucose. glucose can not be released from the glycogen stored in skeletal muscles to create energy. People with type V GSD experience problems performing and completing most exercises, especially anaerobic exercises.

14. Regulation of blood glucose by Hormones The hormones that are responsible for blood glucose regulation are present in balance. This balance is formed of insulin, which tends to decrease the blood glucose and anti-insulin hormones that tend to maintain the blood glucose during fasting and carbohydrate deficiency and to supply more glucose to the blood during stress or muscular exercise.

16. A- Insulin: It is secreted by the �-cells of pancreatic islets in response to hyperglycemia. It produces its effects through the following mechanisms:- * It increases the uptake of glucose by extrahepatic tissues (heart, skeletal muscles and adipose tissues). * It increases utilization of glucose (oxidation, glycogenesis and lipogenesis) in different tissues. * It decreases out put of glucose by liver(decreases glycogenolysis and gluconegenesis).

17. B-Anti- Insulin hormones: 1-Glucagon: -It is hyperglycemic hormone(counter-regulatory hormone). - lt is produced by a cells of pancreatic islets. -It consists of single polypeptide chain. -Its secretion is increased by fasting or any drop in blood glucose. Insulin/ glucagon ratio is the main regulator of blood glucose. -Its secretion is inhibited by high blood glucose and insulin. -Action of glucagon on CHO occurs through formation of cAMP--------->increased glycogenolysis and increased gluconegensis. It inhibits glycolysis and glycogenesis.

18. 2- Epinephrine (Adrenaline): -It is counter� regulatory hormone (hyperglycemic hormone). -It is produced by adrenal medulla and secreted in large amounts in cases of stress, trauma, severe exercise,hypoxia, anaesthesia (emergency hormone). -It stimulates the release of glucagon and inhibits insulin sercretion. - It increases glycogenolysis(through cAMP)in liver and muscles and inhipit glycogenesis. In adipose tissue, it stimulates lipolysis which increases F.A.release and oxidation. Increased secretion of adrenaline can produce D.M.( emotional or stress D.M.) - It decreases the uptake of glucose by the tissues.

19. 3. Cortisol : - This glucocorticoid is secreted by the adrenal cortex. - It stimulates protein catabolism, and gluconeogenesis from amino acids. - In extrahepatic tissues, it decreases glucose utilization . - It stimulates lipolysis in adipose tisues. - Hypersecretion of glucocorticoids may produce D.M.(Steriod D.M.) as in cushing syndrome. D.M.may be produced by prolonged administration of cortisone or its derivatives.

20. 4.Growth hormone (GH): -It is counter-regulatory hormone secreted by the anterior pituitary gland in response to abnormal low blood glucose level. -The hypothalamic glucoreceptors can trigger both the release of growth hormone and ACTH and the secretion of epinephrine (mediated by the autonomic nervous system) when the blood glucose level is abnormally low, -Growth hormone (and cortisol) are less important in the short-term maintenance of blood glucose concentration, rather they play a role in the long-term management of glucose metabolism. -It decrease utilization of glucose in many tissues and stimulates gluconeogenesis in the liver through induction of trnsaminases. -it stimulates lipolysis in adipose tissues. -Hypersecretion of GH can produce DM (pituitary DM)

21. 5.Thyroid hormones (TH): Thyroxine affects the blood glucose is elevated in hyperthyroid patients and decreased in hypothyroidism. Prolonged un treated hyperthyroidism can produce DM. Thyroxine increases all aspects of CHO metabolism by stimulating: Insulin secretion and catabolism Glucose absorption by intestine Glucose uptake and utilization by tissues Glycogenolysis and gluconeogenesis. >>increases blood glucose

22. Abnormalities of Blood glucose levels These may be in the form of hyperglycemia (or diabetes mellitus ) and hypoglycemia. Diabetes mellitus will be explained later on and it is due to decreased insulin secretion and action or hyper secretion of anti-insulin hormones.

23. GLYCOSURIA It is the presence of abnormal amounts of any sugar in urine. It is futher classified according to the sugar present into the following types: 1-Glucosuria: It is the presence of glucose in urine in amounts (less than 30 mg/dl) detectable by ordinary routine methods (Fehling's &Bendict's tests and urinary strips) .

24. It is produced by the following causes: A- Hyperglycemia glucosuria: It occurs when the blood glucose level exceeds the renal threshold (180mg/dl).it is caused by : -Diabetes mellitus . -Epinephrine glucosuria as emotional or stress glucosuria or in case of pheochromocytoma (epinephrine secreting tumor). -Alimentary glucosuria It is due to increased rate of glucose absorption as in cases of gastrectomy or gastrojejunostomy. -Experimental glucosuria: a)Alloxan diabetes ;destroy the Beta cells of pancreas. b)Diabetes with pancreatectomy.

25. B-Normoglycemic or renal glucosuria: In these cases,the blood glucose is within normal range 1-Congenital renal glucosuria (benign glucosuria or diabetes innocens),due to congenital defects in renal tubular mechanism for reabsorption of glucose. 2-Acquired renal diseases as in nephritis. 3-Phlorhizin produces this type of glucosuria due to inhibition of the sodium dependent glucose transporter in renal tubules. It is one type of experimental glucosuria .

26. 2-Fructosuria: 1-Alimentary fructosuria:following ingestion of large amount of fructose. 2-Essential fructosuria due to hereditary deficiency of fructokinase. 3-Galactosuria: 1-Alimentary :following by ingestion of large amounts of galactose,particularly in patients with hepatic function impairment. 2-In cases of galatosemia (see galactose metabolism).

27. 4-Lactusuria: This normally appears in urine in late monthes of pregnancy and during lactation.