Updated: 9/22/2018

Glycogen

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Overview
  •  Structure
    • glycogen
      • polymer of glucose
        • straight chain with α-1,4-bond
        • branches with α-1,6-bond
    • glycogen granule
      • core
        • glycogenin
  • Function
    • energy reserves that can provide glucose during a fast or ↑ energy demand
      • supplies exhausted in < 24 hrs
    • stored mainly in the liver and muscle
      • muscle does not have glucose-6-phosphatase so it cannot release free glucose
        • stores for its own consumption
      • liver does have glucose-6-phosphatase so it can release free glucose
        • can use supplies to maintain blood glucose levels
Glycogenesis
  • Glycogen synthesis 
  • Pathway
    • glucose-6-phosphate converted to glucose-1-phosphate
    • UDP group added to form UDP-glucose
    • UDP-glucose added to polymer in an α-1,4 linkage
      • catalyzed by glycogen synthase
        • rate limiting step of glycogen synthesis
    • polymer rearranged to create α-1,6 linked branches
      • catalyzed by branching enzyme
        • deficiency = Anderson disease
  • Regulation
    • glycogen synthase
      • in liver
        • activated by insulin
        • inhibited by glucagon, epinephrine
      • in muscle
        • activated by insulin
        • inhibited by epinephrine
Glycogenolysis
  • Glycogen catabolism
  • Pathway
    • glucose-glucose bond broken by addition of a phosphate
      • catalyzed by glycogen phosphorylase
        • rate limiting step of glycogenolysis
          • hepatic deficiency = Hers disease (type VI)
          • muscle deficiency = McArdle disease (type V)
    • glucose-1-phosphate freed
      • converted to glucose-6-phosphate
    • debranching enzymes removes α-1,6 linked branches
      • deficiency = Cori's disease (type III) 
    • liver converts glucose-6-phosphate to glucose
      • catalyzed by glucose-6-phosphatase
        • deficiency = von Gierke disease (type I)
    • muscle puts glucose-6-phosphate into glycolysis
  • Regulation
    • glycogen phosphorylase
      • in liver
        • activated by epinephrine, glucagon
          • via cAMP/protein kinase A
        • inhibited by insulin
        • remember: exact opposite of glycogen synthase
          • hepatic glycogen regulatory processes both turn on forward direction and turn off reverse
      • in skeletal muscle
        • activated by epinephrine, AMP, Ca2+
        • inhibited by insulin, ATP
        • remember: since muscular glycogen can only supply itself, it is regulated by its own energy supply (AMP/ATP ratio); while liver must supply energy to many other tissues, it functions independently of AMP/ATP ratio in hepatocytes
Glycogen Storage Diseases (Glycogenolyses)
  • Overview 
    • all disorders have abnormal glycogen metabolism
      • leads to an accumulation of glycogen within cells
      • organ dysfunction
    • remember: disorders numbered in order of pathway from end (glucose release) to beginning (breakdown of glycogen polymer)
  • Glucose release
    • Type I: von Gierke 
      • lacks glucose-6-phosphatase
      • presentation
        • liver cannot release stored glucose
          • hepatomegaly
          • severe hypoglycemia
        • body must rely on fat/protein catabolism for energy
          • hyperlipidemia
          • hyperuricemia
          • lactic acidosis
        • normal glycogen structure
      • tests 
        • stimulation test with glucagon, fructose, galactose
        • does not ↑ serum glucose
  • Lysosomal pathway
    • Type II: Pompe "trashes the Pump (heart)" 
      • lacks lysosomal α1,4-glucosidase
        • degrades glycogen-resembling material in endosomes
      • presentation
        • buildup of glycogen in cardiac muscle
          • electron dense granules inside lysosomes
          • cardiomegaly
          • hypertrophic cardiomyopathy
  • Branching/debranching
    • Type III: Cori 
      • lacks debranching enzyme
        • remember:
          • Cori = can't Catabolize branches
          • 6-pack core - alpha 1,6 glucosidase defective
      • presentation
        • liver cannot break down glycogen past a branch point
          • hepatomegaly
          • hypoglycemia
          • abnormal glycogen structure
            • short outer glycogen chains
    • Type IV: Anderson
      • lacks branching enzyme
        • remember: Anderson = can't Add branches
      • presentation
        • liver cannot form branched glycogen granules
          • hypotonia
          • cirrhosis
  • Phosphorylase
    • Type V: McArdles 
      • lacks muscle phosphorylase
        • remember: McArdles = Muscle
        • can't breakdown glycogen to glucose-1-phosphate 
      • presentation 
        • muscle weakness/cramps upon exertion
        • myoglobinuria
        • normal glycogen structure
    • Type VI: Hers
      • lacks hepatic phosphorylase
        • remember: Hers = Hepatic
      • presentation
        • hepatomegaly
        • fasting hypoglycemia
          • can be mild due to gluconeogenic compensation
 
 

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Questions (8)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.BC.74) You are presented with an infant boy who has repeatedly experienced hypoglycemia and seizures. On your exam, you note decreased muscle tone, growth retardation, and hepatomegaly. The patient has normal serum lactate. You review results of a liver biopsy, shown in Figure A. Further biochemical testing reveals glycogen with abnormally short outer chains. Which of the following enzymes is most likely deficient in this patient? Review Topic

QID: 106621
FIGURES:
1

Muscle glycogen phosphorylase

8%

(15/193)

2

Alpha-1,6-glucosidase

40%

(77/193)

3

Glucose-6-phosphatase

15%

(28/193)

4

Acid maltase

2%

(4/193)

5

Branching enzyme

34%

(65/193)

M1

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(M1.BC.74) A 12-year-old male presents to the pediatrician after two days of tea-colored urine which appeared to coincide with the first day of junior high football. He explains that he refused to go back to practice because he was humiliated by the other players due to his quick and excessive fatigue after a set of drills accompanined by pain in his muscles. A blood test revealed elevated creatine kinase and myoglobulin levels. A muscle biopsy was performed revealing large glycogen deposits and an enzyme histochemistry showed a lack of myophosphorylase activity. Which of the following reactions is not occuring in this individuals? Review Topic

QID: 106612
1

Converting glucose-6-phosphate to glucose

3%

(1/38)

2

Breaking down glycogen to glucose-1-phosphate

84%

(32/38)

3

Cleaving alpha-1,6 glycosidic bonds from glycogen

5%

(2/38)

4

Creating alpha-1,6 glycosidic bonds in glycogen

3%

(1/38)

5

Converting galactose to galactose-1-phosphate

0%

(0/38)

M1

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