Updated: 12/21/2018

Microtubules

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Overview
  • IntroductioThis illustration highlights the basic components and structure of a microtubule. Microtubules are composed of alpha and beta tubulin proteins. These tubulin dimers form a protofilament, which then associate laterally with adjacent protofilaments (usually 13) to yield a microtubule. Kinesin and Dynein are involved in anterograde and retrograde transport, respectively. n
    • cellular structural protein with a hollow tubular structure
  • Structure
    • composed of polymerized dimers of α- and β-tubulin
      • each dimer has 2 GTP molecules bound
    • constant assembly (slow) and disassembly (fast)
      • clinical importance
        • Chédiak–Higashi syndrome (CHS)
          • etiology
            • a disease caused by a microtubule polymerization defect
          • resulting in decreased chemotaxis, degranulation, phagocytosis
          • AR inheritance
          • presentation
            • recurrent pyogenic infections
              • particularly S. aureus
            • partial albinism
            • peripheral neuropathy
  • Function
    • component of many important cellular structures
      • cilia
        • 9+2 arrangement of microtubules
        • axonemal dynein
          • ATPase that attaches the peripheral 9 doublets
          • causes bending of cilium by binding differentially to doublets
        • also forms the core of flagella
        • clinical importance
          • Kartagener syndrome  
            • immotile cilia disease
            • cause
              • dynein arm defect 
            • presentation
              • male and female infertility
                • sperm are immotile (no functional flagellar tail)
                • Fallopian tubes cannot sweep egg and sperm towards each other 
              • bronchiectasis
              • recurrent sinusitis
                • mucus with bacteria and particles cannot be removed
              • associated with situs inversus
      • mitotic spindles
      • molecular motor proteins 
        • mediates intracellular transport
        • 2 types
          • kinesin
            • cell center → periphery
            • anterograde to microtubule
            • e.g. transports neurotransmitter vesicles down axon towards synapse
          • dynein 
            • periphery → cell center
            • retrograde to microtubule
            • e.g. lipid transport from synapse back to Golgi apparatus
  • Pharmacologic importance
    • mebendazole
      • class: antihelminthic
      • mechanism of action
        • microtubule synthesis in worms
    • griseofulvin
      • class: antifungal
      • mechanism of action
        • deposits in new keratin and disrupts microtubule polymerization
      • uses
        • active against dermatophytes only
    • vincristine/vinblastine 
      • class: anti-cancer
      • mechanism of action
        • ↓ microtubule polymerization
          • inhibits mitosis
      • side effects
        • peripheral neuritis
        • areflexia
        • myelosuppression
    • paclitaxel (taxol)
      • class: anti-breast cancer
      • mechanism
        • ↑ stability of microtubule and does not allow disassembly
          • inhibits mitosis
    • colchicine 
      • class: anti-gout
      • mechanism of action
        • binds free tubulin
        • ↓ microtubule polymerization
          • inhibits leukocyte/granulocyte migration
 

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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) A 29-year-old male presents with his wife to his primary care physician with a complaint of infertility. His medical history is significant for recurrent respiratory infections since he was a child. Semenalyis is ordered and reveals significantly reduced sperm motility. To confirm the suspected diagnosis, the physician orders a chest radiograph, which is shown in Figure A. Which of the following is the cause of this patient's condition? Review Topic

QID: 106657
FIGURES:
1

Microtubule polymerization defect

6%

(1/16)

2

Kinesin protein mutation

0%

(0/16)

3

Sphingomyelinase deficiency

0%

(0/16)

4

Dynein arm defect

88%

(14/16)

5

LFA-1 integrin (CD18) defect

0%

(0/16)

M1

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(M1.BC.74) A 52-year-old man awakens in the middle of the night with excruciating pain in his right great toe. He reports that even the touch of the bed sheet was unbearably painful. His right foot is shown in figure A. He is treated with colchicine. Which of the following describes the mechanism of colchicine? Review Topic

QID: 106643
FIGURES:
1

Inhibition of xanthine oxidase

18%

(36/203)

2

Inhibition of reabsorption of uric acid in proximal convoluted tubule

13%

(26/203)

3

Nonselective inhibition of cyclooxygenase (COX) 1 and 2

5%

(11/203)

4

Binds to glucocorticoid receptor

0%

(0/203)

5

Decreases microtubule polymerization

63%

(127/203)

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(M1.BC.70) In large neurons the nucleus can be found a large distance away from the terminal end of its axon. The body has a complex system of intracellular transporters that are able to carry essential proteins from the nucleus to the distal edge of the cell and back. Which of the following proteins are essential for this function? Review Topic

QID: 106481
1

Kinesin, Troponin

10%

(2/21)

2

Dynein, Kinesin

90%

(19/21)

3

Actin, Dynein

0%

(0/21)

4

Myosin, Kinesin

0%

(0/21)

5

Glucose, Actin

0%

(0/21)

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(M1.BC.32) Which of the following cells in the body depends on dynein for its unique functioning? Review Topic

QID: 101696
1

Lower esophageal mucosal cell

2%

(5/280)

2

Fallopian tube mucosal cell

77%

(216/280)

3

Small intestinal mucosal cell

3%

(9/280)

4

Skeletal muscle cell

12%

(35/280)

5

Adipocyte

2%

(7/280)

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