Updated: 1/10/2018

Gluconeogenesis

Topic
Review Topic
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Questions
6
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Evidence
2
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Overview
  •  Function
    • de novo glucose synthesis
      • effectively glycolysis in reverse
      • can maintain blood glucose when glycogen stores are exhausted
      • must supply brain and RBCs which utilize glucose for energy
        • is NOT a source of energy for the liver
          • hepatocytes use β-oxidation to supply the energy needed for gluconeogenesis
    • potential substrates
      • all amino acids
        • except for leucine and lysine 
      • lactate
        • produced in anaerobic glycolysis
      • glycerol-3-phosphate
        • produced in fat catabolism
      • propionyl-CoA
        • produced in odd-carbon fatty acid catabolism
  • Pathway
    • location 
      • hepatocytes (primary)
      • kidney
      • enterocytes
      • NOT muscle
        • no glucose-6-phosphatase
          • cannot release free glucose
    • enzymes  
      • involves both mitochondrial and cytosolic enzymes
      • several steps of glycolysis are reversible
      • the non-reversible steps must be bypassed with special gluconeogenic enzymes
        • pyruvate carboxylase
          • pyruvate → oxaloacetate
          • requires biotin and ATP
          • activated by acetyl-CoA
            • oxaloacetate must be converted to malate to exit the mitochondria via the malate-aspartate shuttle
          • in mitochondria
        • PEP carboxykinase (PEPCK)
          • oxaloacetate → phosphoenolpyruvate (PEP)
          • requires GTP
          • activated by glucagon and cortisol
          • in both cytosol and mitochondria
        • fructose-1,6-bisphosphatase 
          • fructose-1,6-bisphosphate → fructose-6-P
          • important control point of gluconeogenesis
          • activated by ATP, inhibited by AMP and fructose-2,6-bisphosphate
          • in cytosol
        • glucose-6-phosphatase (G6P)
          • glucose-6-P → glucose
          • in ER of hepatocytes
          • clinical relevance
            • von Gierke disease = G6P deficiency
              • see Glycogen metabolism
      • other enzymes
        • lactate dehydrogenase
          • lactate → pyruvate
          • requires free NAD+
    • regulation
      • stimulation
        • glucagon
        • acetyl CoA
        • citrate
      • inhibition
        • high NADH/NAD+ ratio
          • alcohol may cause elevated NADH/NAD+ ratio leading to hypoglycemia  
 
 

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Questions (6)
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) The balance between glycolysis and gluconeogenesis is regulated at several steps, and accumulation of one or more products/chemicals can either promote or inhibit one or more enzymes in either pathway. Which of the following molecules if increased in concentration can promote gluconeogenesis? Review Topic

QID: 106607
1

AMP

12%

(13/111)

2

ADP

19%

(21/111)

3

Insulin

5%

(6/111)

4

Fructose-2,6-biphosphate

23%

(26/111)

5

Acetyl-CoA

40%

(44/111)

M1

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PREFERRED RESPONSE 5
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(M1.BC.2) A 65-year-old homeless man with a history of hospitalization for alcohol intoxication is brought in confused. His serum glucose is 39mg/dl. Which of the following is likely true? Review Topic

QID: 100067
1

He has also been using cocaine

1%

(2/325)

2

He has decreased activity of alcohol dehydrogenase

9%

(29/325)

3

Hepatic gluconeogenesis is elevated

7%

(23/325)

4

The next step in management is glucose repletion

21%

(67/325)

5

His hepatic NADH/NAD+ ratio is high

62%

(200/325)

M1

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PREFERRED RESPONSE 5

(M1.BC.1) To prepare for an endoscopy, a 27-year-old male was asked by the gastroenterologist to fast overnight for his 12 p.m. appointment the next day. Therefore, his last meal was dinner at 5 p.m. the day before the appointment. By 12 p.m. the day of the appointment, his primary source of glucose was being generated from gluconeogenesis, which occurs via the reversal of glycolysis with extra enzymes to bypass the irreversible steps in glycolysis. Which of the following irreversible steps of gluconeogenesis occurs in the mitochondria? Review Topic

QID: 106291
1

Glucose-6-phosphate to glucose

3%

(1/36)

2

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

11%

(4/36)

3

Pyruvate to oxaloacetate

69%

(25/36)

4

Phosphoenolypyruvate to pyruvate

8%

(3/36)

5

Glucose-6-phosphate to 6-phosphogluconolactone

3%

(1/36)

M1

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PREFERRED RESPONSE 3
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