Cellular Biochemistry Flashcards
What are the regulators for transition(s) between the cell cycle phases?
Cyclins: phase-specific regulatory proteins that activate CDKs
CDKs (cyclin-dependent kinases): constitutive and inactive
Cyclin-CDK complexes: phosphorylate other proteins to coordinate cell cycle progression
Tumor Suppressors: p53 induces p21, which inhibits CDKs, leading to hypophosphorylation (activation) of Rb and consequent inhibition of G1-S progression.
First Aid, page 42
What are Nissl bodies?
Nissl bodies are RER in neurons and are the site of secreted peptide neurotransmitters.
RER are the sites of synthesis for secreted proteins. Mucus-secreting goblet cells of small intestines and antibody-secreting plasma cells are rich in RER.
First Aid, page 42
Role of smooth ER? Examples of cells rich in smooth ER?
Site of steroid synthesis and drug/poison detoxification.
Liver hepatocytes and steroid hormone-producing cells of adrenal cortex and gonads are rich in smooth ER.
First Aid, page 42
Role of Golgi and endosomes? What are the different types of modifications performed within the golgi?
Golgi acts as the distribution center fr proteins/lipids from the ER to vesicles and plasma membrane. It adds mannose-6-phosphate to proteins for trafficking to lysosomes. Modifies N-oligosaccharide on asparagine. Adds O-oligosaccharide on serine and threonine.
Endosomes are sorting centers for material from outside cell or from Golgi, sending it to lysosomes for destruction OR back to membrane/Golgi for further use.
First Aid, page 42
I-cell disease (inclusion cell disease, mucolipidosis type II) pathophysiology? Symptoms?
Inherited lysosomal storage disorder in which defect in N-acetylglucosaminyl-1-phosphotransferase leads to failure of Golgi to phosphorylate mannose residues on glycoproteins. This results in extracellular secretion of proteins instead of delivery to lysosomes.
Symptoms include coarse facial features, clouded corneas, restricted joint movements, and high plasma levels of lysosomal enzymes.
Often fatal in childhood.
First Aid, page 43
SRP/signal recognition particle? Result if absent/dysfunctional?
Cytosolic ribonucleoprotein that traffics proteins from ribosome to RER.
If absent/dysfnctional, can result in protein accumulation in cytosol.
First Aid, page 43
Direction of transport for the following vesicular trafficking proteins?
COP I (retrograde): Golgi –> Golgi; cis-Golgi –> ER
COP II (anterograde): ER –> cis-Golgi
“TWO steps forward, ONE step back.”
Clathrin: trans-Golgi –> lysosomes; plasma membrane –> endosomes (receptor-mediated endocytosis, eg LDL-receptor activity)
First Aid, page 43
Which tissue is each of following intermediate filament specific for in IHC staining:
1) Vimentin
2) Desmin
3) Cytokeratin
4) GFAP (glial fibrillary acid proteins)
5) Neurofilaments
1) Mesenchymal tissues (fibroblasts, endothelial cells, macrophages)
2) Muscle
3) Epithelial cells
4) Neuroglia (astrocytes, Schwann cells, oligodendrocytes)
5) Neurons
First Aid, page 44
Structure of microtubules? Function?
Cylindrical outer structure composed of helical array of polymerized heterodimers of alpha and beta tubulin. Each dimer has 2 GTP bound.
Incorporated into flagella, cilia, and mitotic spindles for movement/cell division. Also involved in axoplasmic transport in neurons.
First Aid, page 44
Function of molecular motor proteins dynein and kinesin?
Transport of cellular cargo towards specific end of microtubule track.
Dynein: retrograde transport (+ –> - end of microtubule)
Kinesin: anterograde transport (- –> + end of microtubule)
First Aid, page 44
Kartagener syndrome (primary ciliary dyskinesia) pathophysiology? Symptoms?
Immotile cilia due to dynein arm defect.
Decreased male/female infertility due to immotile sperm and dysfunctional fallopian tube cilia, respectively.
Can cause bronchiectasis, recurrent sinusitis, chronic ear infections, conductive hearing loss, and situs inversus (eg dextrocardia on CXR).
First Aid page 45, Pathoma page 91
Sodium-potassium pump function? MoA for cardiac glycosides: Ouabain and digoxin/digitoxin?
Na+/K+ ATPase located in plasma membrane with ATP site on cytosolic side.
For each ATP consumed, 3Na+ is pumped out (pump phosphorylated) and 2K+ enters cell (pump dephosphorylated).
Oubain inhibits by binding to K+ site.
Digoxin/digitoxin directly inhibits Na+/K+ ATPase, which leads to indirect inhibition of Na+/Ca2+ exchange –> increases intracellular [Ca2+] –> increases cardiac contractility.
First Aid, page 45
What are the different types of collagen? What types of tissue do they make up? What are some of the associated conditions with deficiency of each type?
Be (So Totally) Cool, Read Books
Type I: bone (made by osteoblasts), skin, tendon, dentin, fascia; associated with osteogenesis imperfectat
Type II: cartilage (carTWOlage)
Type III: Reticulin (skin, blood vessels, uterus, fetal tissue, granulation tissue); associated with uncommon, vascular Ehlers Danlos (classic type is type V collage with joint and skin symptoms)
Type IV: Basement membrane, basal lamina, lens; associated with Alport syndrome, Goodpasture syndrome
Type V: dermal/epidermal junction, placental tissue; associated with most common type of Ehlers Danlos
Fist Aid, page 46
Process of collagen synthesis? How do defects in each step result in disease?
1) Synthesis: translation of preprocollagen (collagen alpha chains), usually Gly-X-Y (X = Pro, Y = Lys)
2) Hydroxylation of specific Pro/Lys residues that requires Vitamin C; deficiency = scurvy
3) Glycosylation of pro-alpha-chain residues to form procollagen via hydrogen and disulfide bonds –> triple helix; problems forming triple = osteogenesis imperfecta
4) Exocytosis of procollagen into extracellular space
5) Proteolytic processing via cleavage of disulfide-rich regions of procollagen terminals to form insoluble tropocollagen; problems with cleavage = Ehlers-Danlos
6) Cross-linking of lysine-hydroxylysine reinforces staggered tropocollagen to make collagen fibrins; problems with cross-linking = Ehlers Danlos, Menkes disease
First Aid, page 46
Osteogenesis imperfecta (“brittle bone disease”) pathophysiology? Symptoms?
Most common gene defects = COL1A1 and COL1A2 to result in autosomal dominant form of disease that results in decreased production of normal type I collagen
BITE:
1) Bone fractures
2) I (eye) - blue sclera due to translucent connective tissue over choroidal veins
3) Teeth - dental imperfections due to lack of dentin dentinogenesis imperfecta)
4) Ear - hearing loss due to abnormal ossicles
First Aid, page 47
Ehlers Danlos syndrome pathophysiology? Symptoms?
Multiple types that can be either autosomal dominant or recessive.
Classical type = type V collagen mutation (COL 5A1, COL 5A2) resulting in joint/skin symptoms (joint dislocation, skin hyperextensibility)
Vascular type = type III collagen deficiency resulting in berry/aortic aneurysms, organ rupture
First Aid, page 47
Menkes Disease pathophysiology? Symptoms?
X-linked recessive connective tissue disease caused by impaired copper absorption and transport due to defective Menkes protein (ATP7A).
Leads to decreased lysyl oxidase (for which copper is cofactor) activity.
Results in brittle “kinky” hair, growth retardation, and hypotonia.
First Aid, page 47
What the different cell types based on ability to regenerate? Give examples of each type.
Permanent: Remain in G0 phase and regenerate from stem cells. (neurons, skeletal/cardiac muscles, RBCs).
Stable (quiescent): Can enter G1 from G0 when initiated. (hepatocytes, lymphocytes).
Labile: Never go into G0 and can divide rapidly with short G1. MOST AFFECTED by chemotherapy. (bone marrow, gut epithelium, skin, hair follicles, germ cells).
Role of peroxisomes?
Membrane-enclosed organelle involved in catabolism of very-long-chain fatty acids (via beta-oxidation), branched fatty acids, amino acids, and ethanol.
Zellweger and Refsum disease?
Both are peroxisome biogenesis disorders among the Zellweger spectrum, Zellweger disease being more severe than Refsum.
Both are due to AR mutations.
Zellweger disease usually have symptoms of hepatomegaly, hypotonia, and seizures and infants usually do not survive past year one.
Refsum disease have symptoms of scaly skin, ataxia, cataracts/night blindness, shortened 4th toe, epiphyseal dysplasia.
See First Aid page 43.
Role of proteasomes?
Proteasomes degrade damaged or ubiquitin-tagged proteins.
See First Aid page 43.
What are the different types of cytoskeletal filaments? Their main function(s)? Examples of each?
Microfilaments - muscle contraction, cytokinesis (actin, microvilli)
Intermediate filaments - maintain cell structure (vimentin, desmin, cytokertain, lamins, etc.)
Microtubules - movement, cell division (cilia, flagella, mitotic spindle, axonal trafficking, centrioles)
See First Aid page 43.
What type of cells/tissues do IHC stains for intermediate filaments help identify? Types of tumors that can be identified?
ViMEntin - MEsenchymal tissues (fibroblasts, endothelial cells, macrophages) –> mesenchymal tumors (sarcomas), endometrial carcinomas, RCCs, meningiomas
DesMin - Muscle –> rhabdosarcoma
Cytokeratin - epithelial cells –> SCC
GFAP - neuroGlia (astrocytes, Schwann cells, oligodendrocytes) –> astrocytoma, glioblastoma
Neurofilaments - neurons –> neuroblastoma
See First Aid page 44, Pathoma page 29
What is the structure of cilia? What are basal body and axonemal dynein?
Cilia is composed of peripheral 9 doublet + central 2 singlet arrangement of microtubules.
Basal body is located at the base of cilium below cell membrane. It is composed of 9 microtubule TRIPLETS with NO central microtubules.
Axonemal dynein is an ATPase that links peripheral 9 doublets to each other to cause bending of cilium by differential sliding of doublets.
See First Aid page 45
What are the components of elastin? How is it broken down?
Elastin is rich in NON-hydroxylated proline, glycine, and lysine residues (unlike collagen, which is composed of hydroxylated lysine). It is formed by precursor tropoelastin with fibrillin scaffolding.
Elastin is broken down by elastase, whose enzymatic activity is regulated by alpha1-antitrypsin (A1AT).
A1AT deficiency can result in excess elastase activity to cause rare for of emphysema. Mutant A1AT can also accumulate in hepatocyte ER to cause liver damage.
See First aid page 48 and 375, Pathoma page 90.
Marfan Syndrome
AD mutation of fibrillin gene FBN1 on chromosome 15.
Findings: tall, long extremities, pectus carinatum (more specific) or excavatum, hypermobile joints, cystic medial necrosis of aorta, aortic aneurysms/dissections, floppy mitral valve, lens subluxation (usually upward and temporally).
See First Aid page 48
