A patient presents with blue sclera that results in an inability to form procollagen from pro-α chains. What disease does he have?
Osteogenesis imperfecta
List the four main phases of mitosis in order.
Prophase, metaphase, anaphase, and telophase
When does mitosis occur in the cell cycle?
Mitosis occurs after G2 and before G1 in the cell cycle
When does DNA synthesis occur in the cell cycle?
After G1 and before G2 in the cell cycle
In this image, what two tumor suppressor genes normally inhibit G1-to-S progression?
Rb and p53
During which phase of the cell cycle can a cell enter G0?
G1
Which phase of the cell cycle is usually the shortest?
Mitosis
Which phase of the cell cycle is shortened in rapidly dividing cells?
G1
What is the relationship between cyclin-dependent kinases and cyclins?
Cyclins are regulatory proteins that are translated and activate cyclin-dependent kinases at appropriate times in the cell cycle
Permanent and stable cells are typically in which phase of the cell cycle?
G0
Rb and p53 tumor suppressors prevent which transition in the cell cycle?
Transition from G1 to S phase; defective cells are not allowed to undergo DNA synthesis
_____ (Permanent/stable/labile) cells remain in G0 and regenerate from stem cells.
Permanent
_____ (Permanent/stable/labile) cells enter G1 from G0 when stimulated.
Stable
_____ (Permanent/stable/labile) cells never go to G0 and divide rapidly with a short G1.
Labile
Neurons, skeletal and cardiac muscle, and red blood cells are examples of _____ (permanent/stable/labile) cells.
Permanent
Hepatocytes and lymphocytes are examples of _____ (permanent/stable/labile) cells .
Stable
Name four examples of labile cells
Labile cells (bone marrow, gut epithelium, skin, and hair follicles)
What happens to cell cycling when there is a mutation in a tumor suppressor such as Rb or p53?
There is unrestrained growth in the cell, and thus an increased likelihood to develop a malignancy
List the three components of interphase.
G1, S phase, and G2
What are the main functions of the rough endoplasmic reticulum?
The synthesis of secretory (exported) proteins and the addition of N-linked oligosaccharides to proteins
Name two types of cells that are rich in rough endoplasmic reticulum.
Goblet cells (secrete mucus) and plasma cells (secrete antibodies)
What is the histologic term for rough endoplasmic reticulum in neurons? What substances are synthesized there?
Nissl bodies, which are the site of enzyme (such as CHAT) and neuropeptide synthesis
_____ (Free/Attached) ribosomes synthesize cytosolic and organellar proteins, whereas _____ (free/attached) ribosomes synthesize secretory proteins.
Free; attached
List two functions of the smooth endoplasmic reticulum.
Steroid synthesis and the detoxification of drugs and poisons
Give two examples of cells that are rich in smooth endoplasmic reticulum.
Liver hepatocytes and steroid-hormone-producing cells of the adrenal cortex
The Golgi apparatus functions as the distribution center for what?
Synthesized proteins and lipids
List three places to which the Golgi apparatus sends proteins and lipids.
The plasma membrane, lysosomes, and secretory vesicles
Clathrin is a protein that transports vesicles from the trans face of the Golgi apparatus to where?
Clathrin directs from trans-golgi to lysosomes and from plasma membrane to endosome
What type of protein-bound saccharides is modified in the Golgi apparatus?
N-oligosaccharides (on asparagine)
In patients with I-cell disease, the failure to add mannose-6-phosphate to proteins in the Golgi apparatus leads to what deficit?
There is no signal that targets lysosomal enzymes to the lysosome, resulting in exocytosis of the enzymes
A child presents with coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes. What could this patient have?
I-cell disease
How are serine and threonine residues modified in the golgi?
O-oligosaccharides are added
What is the role of coat protein II in vesicular trafficking?
Anterograde transport of rough endoplasmic reticulum to the cis-Golgi
True or False: Proteoglycans get assembled from their component core proteins in the Golgi apparatus.
TRUE
How are proteoglycans modified in the Golgi?
Sulfation
How are tyrosine residues modified in the Golgi?
Sulfation
The golgi adds which marker to proteins to target them to lysosomes?
Mannose-6-phosphate
What is the role of coat protein I in vesicular trafficking?
Retrograde movement from the Golgi apparatus to the endoplasmic reticulum
What is the basic pathophysiologic defect in patients with I-cell disease?
The failure of the addition of mannose-6-phosphate to lysosomal proteins and the resulting pathological exocytosis of enzymes
What is the name of the process by which clathrin transports vesicles from outside the cell to inside the cell through fusion of the two lipid-based membranes?
Receptor-mediated endocytosis
Microtubules are formed from what two protein building blocks?
α-Tubulin and β-tubulin
What syndrome results from a microtubule polymerization defect that leads to impaired lysosomal emptying and poor phagocytosis?
Chediak-Higashi syndrome
Name four cellular structures in which microtubules are found.
Cilia, flagella, mitotic spindle, centrioles
True or False? Microtubule filaments grow rapidly but collapse slowly.
False; they grow slowly and collapse quickly
Are microtubules involved in fast or slow transport along the neuronal axons?
Slow axoplasmic transport
What are the symptoms seen in Chdiak-Higashi syndrome?
Pyogenic infections, partial albinism, and peripheral neuropathy
What drug that is used to treat gout acts on microtubules?
Colchicine
Which two anticancer drugs alter the polymerization of microtubules?
Vincristine and vinblastine
What anticancer drug used to treat breast cancers stabilizes microtubules?
Paclitaxel
What antifungal agent targets microtubules?
Griseofulvin
What antihelminthic drugs target microtubules?
Mebendazole and thiabendazole
What protein is responsible for retrograde transport on the microtubule?
Dynein
What protein is responsible for anterograde transport on the microtubule?
Kinesin
How are cilia structurally composed?
Nine microtubule doublets around two central microtubules
What syndrome results from a defect in the dynein arm of cilia?
Kartagener’s syndrome
What protein causes the movement of the cilia?
Axonemal dynein is an adenosine triphosphatase that causes bending of the cilium
Which diagnosis should you consider in a male with infertility, bronchiectasis and recurrent sinusitis?
Kartagener’s syndrome
True or False? Kartagener’s syndrome causes only male infertility.
False; Kartagener’s syndrome causes infertility in both sexes
A 22-year-old female presents with history of recurrent pneumonia. Subsequent chest x-ray reveals dextrocardia. What is the most likely diagnosis involving these two findings?
Kartagener’s syndrome
What is the underlying cellular malfunction that leads to Kartagener’s syndrome?
Immotile cilia as a result of a dynein arm defect
Microvilli and adhering junctions are composed of which two cytoskeletal elements?
Actin and myosin
Which two cytoskeletal elements are necessary for muscle contraction and cytokinesis?
Actin and myosin
Cilia, flagella, mitotic spindles, neurons and centrioles are all composed of which cytoskeletal element?
Microtubule
Vimentin, desmin, cytokeratin, glial fibrillary acid proteins, and neurofilaments are all examples of which type of cytoskeletal element?
Intermediate filaments
Approximately what percent of the plasma membrane is composed of cholesterol?
50%
Approximately what percent of the plasma membrane is composed of phospholipids?
50%
What is the effect on melting temperature if the content of cholesterol in the plasma membrane is increased?
The melting temperature increases
What is the effect of high cholesterol content on the fluidity of a cell membrane?
Fluidity is decreased
Vimentin stains identify which type of cells?
Connective tissue
Desmin stains identify which type of cells?
Muscle
Cytokeratin stains identify which type of cells?
Epithelial cells
Neurofilament stains identify which type of cells?
Neurons
Glial fibrillary acid protein stains identify which type of cells?
Neuroglia
Na+-K+ adenosine triphosphatase exchanges how many sodium and potassium ions in each cycle?
Three sodium ions out and two potassium ions in per cycle
How many adenosine triphosphates are consumed in one cycle of the Na/K pump?
One
What effect does the inhibition of the Na+-;K+ adenosine triphosphatase by digoxin have on cardiac contractility?
It increases cardiac contractility by increasing intracellular calcium concentration
Where does ouabain bind to the Na+-K+ adenosine triphosphatase?
At the K+ binding site
How does inhibition of Na+- K+ exchange result in increased cardiac contractility?
There is indirect inhibition of Na+- Ca2+ exchange, which results in increased intracellular Ca2+ concentration
What is the most abundant type of collagen?
Type I
What type of collagen is found in teeth?
Type I, which is found in dentin
What type of collagen is found in bone?
Type I
What type of collagen is found in the connective tissue of the uterus?
Type III
What type of collagen predominates in fetal tissue?
Type III
What type of collagen is found in the cornea?
Type I
What type of collagen is found in the basement membrane?
Type IV
During wound healing, type ____ collagen is laid down first as part of granulation tissue. Then, type ____ collagen is produced as part of late wound healing.
III; I
What type of collagen is found in the skin and fascia?
Type I
What type of collagen is found in the vitreous body, the clear gel that fills the space between the lens and the retina?
Type II
What type of collagen is found in the nucleus pulposus, the jelly-like substance in the middle of the spinal disc?
Type II
What type of collagen is found in hyaline cartilage?
Type II
What type of collagen is found in blood vessels?
Type III
What is another name for type III collagen?
Reticulin (reticular means net-like)
What type of collagen is found on the articular surface of joints?
Type II
A triple helix composed of three collagen chains that has not yet been cleaved is referred to as what?
Procollagen
Where does collagen synthesis occur in the cell?
In the rough endoplasmic reticulum
Which amino acids predominate in collagen?
Glycine, proline, hydroxyproline, and hydroxylysine
Which vitamin is required for the hydroxylation of proline and lysine in collagen?
Vitamin C
The conversion of preprocollagen to procollagen requires what process?
Glycosylation
A single-collagen chain during collagen synthesis is referred to as what?
Preprocollagen
What form of collagen is exocytosed from the cell into the extracellular space?
Procollagen
An -OH group is added to _____ and _____ after translation of the collagen chain.
Proline; lysine
British sailors in the 17th century come to you due to an inability to hydroxylate proline and lysine residues for collagen synthesis. What disease do they have, and why do you prescribe limes?
Scurvy, and the limes will supply them with the vitamin C they are deficient in during their long voyage (and earn them the nickname, limeys)
A triple helix that is composed of three collagen chains with the terminal regions cleaved off is referred to as what?
Tropocollagen
Is tropocollagen formed intracellularly or extracellularly?
Extracellularly
What is the name of the enzyme that covalently cross-links lysine residues to hydroxylysine residues?
Lysyl oxidase
Many staggered tropocollagen molecules with covalent lysine-hydroxylysine cross-links are referred to as _____ _____.
Collagen fibrils
Does the formation of tropocollagen from the cleavage of procollagen increase or decrease its solubility?
Decreases; tropocollagen is insoluble.
What are the six steps of collagen synthesis in order?
Synthesis, hydroxylation, glycosylation, exocytosis, proteolytic processing, cross-linking
What disease results in an inability to form procollagen from pro chains?
Osteogenesis imperfecta
Ehlers-Danlos syndrome is a defect of what process?
Collagen synthesis
Ehlers-Danlos syndrome is associated with what defects of the vasculature of the brain?
Berry aneurysms
True or False? All types of Ehlers-Danlos syndrome are transmitted through an autosomal recessive inheritance pattern.
False; Ehlers-Danlos syndrome shows variable inheritance, depending on the type
A patient presents with hyperextensible skin, easy bruising, and hypermobile joints. What is the most likely diagnosis?
Ehlers-Danlos syndrome
What type of collagen is most frequently affected in Ehlers-Danlos syndrome?
Type III collagen (reticulin)
Why might patients with Ehlers-Danlos syndrome have an increased risk of organ rupture?
Poor type III collagen synthesis results in weak connective tissue
What type of inheritance does osteogenesis imperfecta show?
Autosomal dominant
A baby is born with multiple fractures and hearing loss. What finding is expected during the ophthalmologic examination?
Blue sclerae
What is the incidence of osteogenesis imperfecta?
1:10,000
Osteogenesis imperfecta is a defect in what process?
Type I collagen synthesis
What is the common etiology of the blue sclerae and multiple fractures seen in osteogenesis imperfecta?
Both symptoms are due to a loss of normal functioning type I collagen; the blue sclerae result from decreased connective tissue over the choroid in the eye, whereas multiple fractures result from decreased collagen in the bone matrix
Which type of osteogenesis imperfecta is fatal in utero?
Type II
A child seen in the emergency room is found to have multiple healing fractures of different ages. What disease should be ruled out before filing abuse charges against the parents?
Osteogenesis imperfecta
The dental imperfections seen in osteogenesis imperfecta is due to lack of _____ in the teeth?
Dentin
A young woman with blue sclerae also has hearing loss. What is the pathophysiology of her hearing loss?
Abnormal bones of the middle ear
What is the typical inheritance pattern of Alport’s syndrome?
X-linked recessive
What type of collagen is disrupted in Alport’s syndrome?
Type IV collagen
You are seeing a man who has progressive deafness and renal failure. The other males in his family show the same symptoms; what is the likely diagnosis?
Alport’s syndrome, which is typified by progressive hereditary nephritis and deafness
What organ (other than the kidneys and the ears) can be affected in Alport’s syndrome?
This disease may result in ocular lesions
What is the relationship between Alport’s syndrome and Goodpasture’s syndrome?
Both are diseases of type IV collagen (Alport’s is genetic; Goodpasture’s is autoimmune)
What enzyme is inhibited by 1-antitrypsin?
1-Antitrypsin inhibits elastase, which degrades elastin
Marfan’s syndrome is caused by a defect in what protein?
Fibrillin
What is the function of fibrillin?
It acts as a scaffold for tropoelastin
What is a stretchy protein found within lungs, large arteries, elastic ligaments, vocal cords and ligamenta flava (which connect the vertebrae)?
Elastin
Excess elastase activity can result in what lung disorder?
Emphysema: 1-antitrypsin inhibits elastase, which degrades elastin; therefore, a lack of 1-antitrypsin can leads to the loss of elastin in the lungs, thereby resulting in emphysema
Elastin is rich in which two amino acids? Are they glycosylated or nonglycosylated?
Proline and lysine; nonglycosylated
In this image of the Na+-K+ ATPase pump, what are the red ions and what are the blue ions?
Blue ions are sodium; red ions are potassium. There are three sodium ions out and two potassium ions in per cycle
A child has bowed legs and low phosphate levels. His family pedigree is shown. What is the mode of inheritance of this disease?
X-linked dominant; the disease is hypophosphatemic rickets
Muscle biopsy of your patient reveals ragged red fibers. His family pedigree is shown. What is the mode of inheritance of this disease?
Mitochondrial inheritance
What is the likely mode of inheritance of a disease characterized by the pedigree shown?
Autosomal recessive
What is the likely mode of inheritance of a disease characterized by the pedigree shown?
X-linked recessive
