Biochemistry - Cellular Flashcards
1
Q
Cell cycle phases
- Regulation
- Phases
A
- Regulation
- Checkpoints control transitions between phases of cell cycle.
- This process is regulated by cyclins, cyclin-dependent kinases (CDKs), and tumor suppressors.
- Phases
- G1 and G0 are of variable duration.
- G = Gap or Growth.
- S = Synthesis.
- Mitosis (shortest phase of cell cycle) includes prophase, metaphase, anaphase, and telophase.
- G1 and G0 are of variable duration.
2
Q
Regulation of Cell Cycle
- CDKs
- Cyclins
- Cyclin-CDK complexes
- Tumor suppressors
A
- CDKs
- Constitutive and inactive.
- Cyclins
- Regulatory proteins that control cell cycle events
- Phase specific
- Activate CDKs.
- Cyclin-CDK complexes
- Must be both activated and inactivated for cell cycle to progress.
- Tumor suppressors
- p53 and hypophosphorylated Rb normally inhibit G1-to-S progression
- Mutations in these genes result in unrestrained cell division (e.g., Li-Fraumeni syndrome).
3
Q
Cell Types
- Permanent
- Stable (quiescent)
- Labile
A
- Permanent
- Remain in G0, regenerate from stem cells.
- Neurons, skeletal and cardiac muscle, RBCs.
- Stable (quiescent)
- Enter G1 from G0 when stimulated.
- Hepatocytes, lymphocytes.
- Labile
- Never go to G0, divide rapidly with a short G1.
- Most affected by chemotherapy.
- Bone marrow, gut epithelium, skin, hair follicles, germ cells.
4
Q
Rough endoplasmic reticulum
- Definition
- Nissl bodies
- Free ribosomes
A
- Definition
- Site of synthesis of secretory (exported) proteins and of N-linked oligosaccharide addition to many proteins.
- Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells are rich in RER.
- Nissl bodies
- RER in neurons
- Synthesize peptide neurotransmitters for secretion.
- Free ribosomes
- Unattached to any membrane
- Site of synthesis of cytosolic and organellar proteins.
5
Q
Smooth endoplasmic reticulum
A
- Site of steroid synthesis and detoxification of drugs and poisons.
- Lacks surface ribosomes.
- Liver hepatocytes and steroid hormone–producing cells of the adrenal cortex and gonads are rich in SER.
6
Q
Cell trafficking
- Golgi
- Endosomes
A
- Golgi
- The distribution center for proteins and lipids from the ER to the vesicles and plasma membrane.
- Modifies N-oligosaccharides on asparagine.
- Adds O-oligosaccharides on serine and threonine.
- Adds mannose-6-phosphate to proteins for trafficking to lysosomes.
- Endosomes
- Sorting centers for material from outside the cell or from the Golgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use.
7
Q
Cell trafficking: Inclusion cell (I-cell) disease
- Definition
- Findings
A
- Definition
- Inherited lysosomal storage disorder
- Defect in phosphotransferase
- –> failure of the Golgi to phosphorylate mannose residues (i.e., decreased mannose- 6-phosphate) on glycoproteins
- –> proteins are secreted extracellularly rather than delivered to lysosomes
- Findings
- Results in coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes.
- Often fatal in childhood.
8
Q
Cell trafficking:
Signal recognition particle (SRP)
A
- Abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER.
- Absent or dysfunctional SRP –> proteins accumulate in the cytosol.
9
Q
Cell trafficking:
Vesicular trafficking proteins
- COPI
- COPII
- Clathrin
A
- COPI
- Golgi –> Golgi (retrograde)
- Golgi –> ER.
- COPII
- Golgi –> Golgi (anterograde)
- ER –> Golgi.
- Clathrin
- Trans-Golgi –> lysosomes
- Plasma membrane –> endosomes (receptor-mediated endocytosis [e.g., LDL receptor activity]).
10
Q
Peroxisomes & proteasomes
- Perioxisome
- Proteasome
A
- Peroxisome
- Membrane-enclosed organelle involved in catabolism of very-long-chain fatty acids, branched-chain fatty acids, and amino acids.
- Proteasome
- Barrel-shaped protein complex that degrades damaged or ubiquitin-tagged proteins.
- Defects in the ubiquitin-proteasome system have been implicated in some cases of Parkinson disease.
11
Q
Microtubule
- Structure
- Molecular motor proteins
- Drugs that act on microtubules
A
- Structure
- Cylindrical structure composed of a helical array of polymerized heterodimers of α- and β-tubulin.
- Each dimer has 2 GTP bound.
- Incorporated into flagella, cilia, mitotic spindles.
- Grows slowly, collapses quickly.
- Also involved in slow axoplasmic transport in neurons.
-
Molecular motor proteins
- Transport cellular cargo toward opposite ends of microtubule tracks.
- Dynein = retrograde to microtubule (+ –> -).
- Kinesin = anterograde to microtubule (- –> +).
- Drugs that act on microtubules (Microtubules Get Constructed Very Poorly)
- Mebendazole (anti-helminthic)
- Griseofulvin (anti-fungal)
- Colchicine (anti-gout)
- Vincristine/Vinblastine (anti-cancer)
- Paclitaxel (anti-cancer)
12
Q
Cilia
- Cilia structure
- Axonemal dynein
- Kartagener syndrome (1° ciliary dyskinesia)
A
- Cilia structure
- 9 + 2 arrangement of microtubules [A].
- Axonemal dynein
- ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets.
-
Kartagener syndrome (1° ciliary dyskinesia)
- Immotile cilia due to a dynein arm defect.
- Results in male and female infertility due to immotile sperm and dysfunctional fallopian tube cilia, respectively
- ↑ risk of ectopic pregnancy.
- Can cause bronchiectasis, recurrent sinusitis, and situs inversus (e.g., dextrocardia on CXR).
13
Q
Cytoskeletal elements & plasma membrane composition
- Cytoskeletal elements
- Actin and myosin
- Microtubule
- Intermediate filaments
- Plasma membrane composition
A
- Cytoskeletal elements
- Actin and myosin
- Muscle contraction, microvilli, cytokinesis, adherens junctions.
- Actins are long, structural polymers.
- Myosins are dimeric, ATP-driven motor proteins that move along actins.
- Microtubule
- Movement.
- Cilia, flagella, mitotic spindle, axonal trafficking, centrioles.
- Intermediate filaments
- Structure.
- Vimentin, desmin, cytokeratin, lamins, glial fibrillary acid proteins (GFAP),
neurofilaments.
- Actin and myosin
- Plasma membrane composition
- Asymmetric lipid bilayer.
- Contains cholesterol, phospholipids, sphingolipids, glycolipids, and proteins.
- Fungal membranes contain ergosterol.
14
Q
Immunohistochemical stains for intermediate filaments: Cell types stained by…
- Vimentin
- Desmin
- Cytokeratin
- GFAP
- Neurofilaments
A
- Vimentin
- Connective tissue
- Desmin
- Muscle
- DesMin: Muscle
- Cytokeratin
- Epithelial cells
- GFAP
- Neuroglia
- GFAP: NeuroGlia
- Neurofilaments
- Neurons
15
Q
Sodium-potassium pump
- Definition
- Regulation
A
- Definition
- Na+-K+ ATPase is located in the plasma membrane with ATP site on cytosolic side.
- For each ATP consumed, 3 Na+ go out and 2 K+ come in.
- Regulation
- Ouabain inhibits by binding to K+ site.
- Cardiac glycosides (digoxin and digitoxin) directly inhibit the Na+-K+ ATPase, which leads to indirect inhibition of Na+/Ca2+ exchange –> increased [Ca2+]i –> increased cardiac contractility.
17
Q
Collagen synthesis and structure:
Inside fibroblasts
- Inside fibroblasts
- Synthesis
- Hydroxylation
- Glycosylation
- Exocytosis
- Outside fibroblasts
5. Proteolytic processing
6. Cross-linking
A
- Synthesis (RER)
- Translation of collagen α chains (preprocollagen)
- Usually Gly-X-Y (X and Y are proline or lysine).
- Glycine content best reflects collagen synthesis (collagen is 1⁄3 glycine).
- Translation of collagen α chains (preprocollagen)
- Hydroxylation (RER)
- Hydroxylation of specific proline and lysine residues
- Requires vitamin C
- Deficiency –> scurvy.
- Glycosylation (RER)
- Glycosylation of pro-α-chain hydroxylysine residues and formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen α chains).
- Problems forming triple helix –> osteogenesis imperfecta.
- Exocytosis
- Exocytosis of procollagen into extracellular space
- Proteolytic processing
- Cleavage of disulfide-rich terminal regions of procollagen, transforming it into insoluble tropocollagen.
- Cross-linking
- Reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (by Cu2+-containing lysyl oxidase) to make collagen fibrils.
- Problems with cross-linking –> Ehlers-Danlos.
18
Q
Osteogenesis imperfecta
- Definition
- Findings
A
- Definition
- Genetic bone disorder (brittle bone disease [A]) caused by a variety of gene defects.
- Most common form is autosomal dominant with decreased production of otherwise normal type I collagen.
- May be confused with child abuse.
- Findings
- Multiple fractures with minimal trauma
- May occur during the birth process
- Blue sclerae [B] due to the translucency of the connective tissue over the choroidal veins
- Hearing loss (abnormal ossicles)
- Dental imperfections due to lack of dentin
- Multiple fractures with minimal trauma
