Updated: 1/17/2019

Glycolysis

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Overview
  • Function 
    • generation of ATP from glucose via substrate-level phosphorylation (as opposed to oxidative phosphorylation) 
      • used by all cells
        • with O2
          • pyruvate enters citric acid cycle (after being created in glycolysis)
          • NAD+ regenerated via oxidative phosphorylation
        • without O2
          • pyruvate cannot enter citric acid cycle after glycolysis
          • NAD+ must be regenerated via conversion of pyruvate to lactate
            • catalyzed by lactate dehydrogenase
      • only source of energy for RBCs
    • generation of intermediates for other pathways
      • 1,3-BPG
        • intermediate of glycolysis
        • can be converted to 2,3-DPG
          • modifies the hemoglobin-O2 binding curve
            • binds HbA and ↓ binding affinity of O2
            • a compensatory mechanism for ↓pO2
  • Pathway
    • in cytoplasm
    • irreversible
    • net reaction
      • glucose + 2Pi + 2 ADP + 2 NAD+ → 2 pyruvate + 2 ATP + 2 NADH + 2H+ + 2 H2O
  • Important enzymes
    • hexokinase - converts glucose into glucose-6-phosphate allowing "trapping" inside cell 
      • distribution
        • widely present in most body tissues 
          • allows trapping of glucose at all blood glucose levels
      • kinetics 
        • high affinity → low Km
        • low capacity → low Vmax
      • regulation
        • feedback inhibited by glucose-6-phosphate
    • glucokinase (hexokinase IV) 
      • distribution
        • liver
          • liver does not not normally use glucose a fuel so the only function is storing excess glucose following a meal
        • β cells of pancreas
          • uses as a means to measure blood glucose and release insulin accordingly
          • mutated in the monogenenic, autosomal dominant form of diabetes called Maturity Onset Diabetes of the Young type 2 (MODY2)
      • kinetics
        • low affinity → high Km
        • high capacity → high Vmax
      • regulation
        • induced by insulin (to store glucose in liver after a meal)
        • no direct feedback inhibition
    • phosphofructokinase-1 
      • rate-limiting step
      • inhibited by ATP, citrate
      • stimulated by AMP, fructose-2,6-bisphosphate
        • fructose 2,6-bisphosphate synthesized by phosphofructokinase-2
    • pyruvate kinase 
      • catalyzes substrate-level phosphorylation
      • inhibited by ATP, alanine
      • activated by fructose-1,6-bisphosphate
  • Hormonal regulation 
    • fasting state
      • ↑ glucagon → ↑ cAMP → ↑ protein kinase A → ↑ FBPase-2, ↓ PFK-2
    • fed state
      • ↑ insulin → ↓ cAMP → ↓ protein kinase A → ↓ FBPase-2, ↑ PFK-2
Disorders of Glycolysis
  • Pyruvate kinase deficiency 
    • AR (most commonly)
    • pathophysiology
      • ↓ ATP generation
        • inability to maintain Na+/K+ ATPase leads to
          • RBC swelling
          • RBC lysis
      • back up of glycolysis
        • ↑ 2,3-BPG and other glycolytic intermediates
    • presentation 
      • chronic hemolysis
      • ↓ O2 affinity for HbA
        • due to ↑ 2,3-BPG
      • no Heinz bodies
        • unlike glucose 6-phosphate dehydrogenase deficiency
 

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Questions (7)
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) Maturity Onset Diabetes of the Young (MODY) type 2 is a consequence of a defective pancreatic enzyme, which normally acts as a glucose sensor, resulting in a mild hyperglycemia. The hyperglycemia is especially exacerbated during pregnancy. Which of the following pathways is controlled by this enzyme? Review Topic

QID: 106604
1

Glucose --> glucose-6-phosphate

60%

(115/191)

2

Glucose-6-phosphate --> fructose-6-phosphate

13%

(25/191)

3

Fructose-6-phosphate --> fructose-1,6-biphosphate

16%

(31/191)

4

Glyceraldehyde-3-phosphate --> 1,3-bisphosphoglycerate

3%

(6/191)

5

Phosphoenolpyruvate --> pyruvate

5%

(9/191)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.BC.79) A mother brings her newborn baby to the pediatrician after noting that his skin looks yellow. The patient's lactate dehydrogenase is elevated and haptoglobin is decreased. A smear of the child's blood is shown below. The patient is ultimately found to have decreased ability to process phosphoenolpyruvate to pyruvate. Which of the following metabolic changes is most likely to occur in this patient? Review Topic

QID: 106905
FIGURES:
1

Left shift of the oxyhemoglobin curve

44%

(8/18)

2

Right shift of the oxyhemoglobin curve

39%

(7/18)

3

Broadening of the oxyhemoglobin curve

6%

(1/18)

4

Narrowing of the oxyhemoglobin curve

6%

(1/18)

5

Increased ATP availability

0%

(0/18)

M1

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PREFERRED RESPONSE 2
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