Updated: 4/29/2018

Nucleotide Catabolism/Salvage

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Overview
  •  Purine
    • salvage pathway
      • see figure
    • clinical importance
      • adenosine deaminase (ADA) deficiency 
        • defective purine salvage
          • results in excess ATP and dATP
        • prevents DNA synthesis
          • ATP and dATP feedback negatively on ribonucleotide reductase in the synthesis of purines and pyrimidines for DNA replication
          • ↓ lymphocyte count
            • major cause of SCID (severe combined immunodeficiency disease)
              • lack of both T and B cells
        • AR
      • Lesch-Nyhan disease
        • defective purine salvage
        • lacks hypoxanthine guanine phosphoribosyl pyrophosphate transferase (HGPRT) enzyme
        • X-linked recessive 
        • presentation
          • severe CNS symptoms
            • choreoathetosis
            • mental retardation
          • self-mutilation
          • hyperuricemia
            • degradation of all purines since it cannot salvage
      • gout
        • pathophysiology
          • high urate levels due to
            • ↑ in cell breakdown
              • e.g. treatment of large tumor masses with radiation or chemo
            • ↓ in renal excretion (most common cause)
          • results in precipitation of monosodium urate crystals in joints
            • negative birefringence
              • yellow when parallel to slow ray
            • needle shaped
        • presentation
          • recurrent acute arthritis
            • pain in big toe first (podagra)
          • chronic
            • tophi present
              • granulomatous deposition (multinucleated giant cells) of crystals in soft tissue
          • ↑ frequency in men >30 y/o
        • treatment
          • acute → colchicine or indomethacin
          • chronic due to ↓ in renal excretion → probenecid
          • chronic due to ↑ in cell breakdown → allopurinol
  • Pyrimidine
    • salvage
      • may be salvaged by pyrimidine salvage enzymes
    • degradation
      • completely broken down to ammonia
  • Other causes of hyperuricemia
    • ↑ EtOH intake
      • can precipitate an acute gout attack
    • ↑ nucleic acid in diet
      • red meats, organ meats
    • phosphate "trapping" diseases
      • e.g. glucose-6-phosphate deficiency (G6PD), galactose uridyltransferase deficiency
      • caused by an inability to dephosphorylate common metabolites and therefore leads to trapping of phosphate by these metabolites
      • lack of phosphate prevents synthesis of ATP, GTP, plus other nucleotide phosphates
      • ADP. AMP, and other hypophosphorylated bases are salvaged producing uric acid
 

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Questions (4)
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.1) A six-month-old infant presents with chronic, persistent diarrhea, oral thrush, and a severe diaper rash. The infant was treated four weeks ago for an upper respiratory and ear infection. A family history is significant for a consanguineous relationship between the mother and father. Physical examination demonstrates the absence of palpable lymph nodes. Accumulation of which of the following would lead to this disease phenotype? Review Topic

QID: 106240
1

Deoxyadenosine

65%

(190/294)

2

Phenylalanine

8%

(23/294)

3

Galactitol

6%

(18/294)

4

Ceramide trihexoside

13%

(37/294)

5

Sphingomyelin

8%

(23/294)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1

(M1.BC.1) A 3-year-old male was brought to the pediatrician with severe lip lacerations, with a portion of his tongue appearing to be bitten off, as well as missing portions of the fingers on his right hand. A family history is notable for two similar cases in male cousins on the mother's side. A urinalysis revealed a high level of uric acid. Which of the following is the mode of inheritance for this disorder? Review Topic

QID: 106253
1

X-linked recessive

74%

(17/23)

2

X-linked dominant

9%

(2/23)

3

Autosomal dominant

0%

(0/23)

4

Autosomal recessvie

4%

(1/23)

5

Maternally inherited mitochondrial defect

13%

(3/23)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1
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