BIOCHEM Flashcards
Most abundant protein in the human body.
Collagen
Collagen general function
Organizes and strengthens extracellular matrix.
Collagen synthesis and structure
steps inside fibroblasts and where inside of them
- Synthesis (RER)
- Hydroxylation (ER)
- Glycosylation (Golgi)
- Exocytosis
Collagen synthesis and structure steps outside fibroblasts
- Proteolytic processing 6. Cross-linking
Collagen synthesis and structure Synthesis (RER)
Translation of collagen α chains
(preprocollagen)— usually Gly-X-Y polypeptide (X and Y are
proline, hydroxyproline, or hydroxylysine).
Collagen synthesis and structure
Hydroxylation (ER)
Hydroxylation of specific proline and lysine
residues (requires vitamin C).
Collagen synthesis and structure
Glycosylation of pro-α-chain lysine residues and formation of procollagen (triple helix of three collagen α chains).
Glycosylation (Golgi)
Collagen synthesis and structure
Exocytosis of procollagen into extracellular
space.
- Exocytosis
Collagen synthesis and structure
Cleavage of terminal regions of procollagen transforms it into insoluble tropocollagen.
- Proteolytic processing
Collagen synthesis and structure
Reinforcement of many staggered tropocollagen molecules by covalent lysine- hydroxylysine cross-linkage (by lysyl oxidase) to make col- lagen fibrils.
- Cross-linking
Chédiak-Higashi syndrome mech
is due to a microtubule polymerization defect resulting in ↓ phagocytosis
Molecular motors
Dynein =
Kinesin =
Molecular motors
Dynein = retrograde.
Kinesin = anterograde.
Drugs that act on microtubules:
- Mebendazole/thiabendazole (antihelminthic)
- Taxol (anti–breast cancer) 3. Griseofulvin (antifungal) 4. Vincristine/vinblastine (anti-cancer)
- Colchicine (anti-gout)
Vesicular trafficking proteins:
trans-Golgi → lysosomes, plasma membrane → endosomes (receptor-mediated endocytosis).
Clathrin
I-cell disease clinical findings
Characterized by coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes. Often fatal in childhood.
I-cell disease mech
failure of addition of mannose-6- phosphate to lysosome proteins, enzymes are secreted outside the cell instead of being targeted to the lysosome.
what cells are particularly rich in SER.
Liver hepatocytes and steroid hormone–producing cells of the adrenal cortex
Osteogenesis imperfecta 4 findings
- Multiple fractures
- Blue sclerae
- Hearing loss (abnormal middle ear bones)
- Dental imperfections due to lack of dentition
Osteogenesis imperfecta worst type and findings
Type II is fatal in utero or in the neonatal period.
5 Immunohistochemical stains and associated cell types
Vimentin - Connective tissue Desmin - Muscle Cytokeratin - Epithelial cells Glial fibrillary acid proteins (GFAP) - Neuroglia Neurofilaments - Neurons
Stretchy protein within lungs, large arteries, elastic ligaments.
Elastin
Elhers-Danlos syndrome mech and clinical findings
Faulty collagen synthesis (Type III is most frequently affected (resulting in blood vessel instability) causing:
- Hyperextensible skin
- Tendency to bleed (easy bruising)
- Hypermobile joints 4.Associated with berry aneurysms.
Collagen Types Type I
(90%)––Bone, Skin, Tendon, dentin, fascia, cornea, late wound repair.
Collagen Types Type II
Cartilage (including hyaline), vitreous body, nucleus pulposus.
Type II: carTWOlage.
Collagen Types Type III (Reticulin)
skin, blood vessels, uterus, fetal tissue, granulation tissue.
Collagen Types Type IV
Basement membrane or basal lamina.
Type IV: Under the floor (basement membrane)
Cilia structure
9 + + 2 arrangement of microtubules.
Dynein is an ATPase that links peripheral
9 doublets and causes bending of cilium by
differential sliding of doublets.
Microtubule structure
Cylindrical structure 24 nm in diameter and of variable length. A helical array of polymerized dimers of α- and β-tubulin (13 per circumference). Each dimer has 2 GTP bound.
Microtubule functions
has 2 GTP bound. Incorporated into flagella, cilia,
mitotic spindles.Microtubules are also involved in slow axoplasmic transport in neurons.
Vesicular trafficking proteins:
Anterograde, RER → cis-Golgi.
COP II
Vesicular trafficking proteins: Retrograde,
Golgi → ER.
COP I
6 Functions of Golgi apparatus
- Distribution center of proteins and lipids from
ER to the plasma membrane, lysosomes, and secretory vesicles - Modifies N-oligosaccharides 3. Adds O-oligosaccharides 4. Addition of mannose-6- phosphate
- Proteoglycan assembly
- Sulfation
α1-antitrypsin inhibits
elastase
Elastin structure
Rich in proline and lysine, nonhydroxylated forms.
Fetal alcohol syndrome worst window
3–8 weeks
Plasma membrane wrt cholesterol
High cholesterol or long saturated fatty acid content → increased melting temperature and decreased fluidity.
Kartagener’s syndrome mech and clinical findings
Immotile cilia due to a dynein arm defect. Results in male and female infertility (sperm immotile), bronchiectasis, and recurrent sinusitis (bacteria and particles not
pushed out); associated with situs inversus.
what cells are particularly rich in RER.
Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells
SER is the site of
steroid synthesis and detoxification
of drugs and poisons.
RER is the site of
synthesis of secretory (exported) proteins and of N-linked oligosaccharide addition
to many proteins.
Checkpoints control transitions between phases. Regulated by
cyclins, cdks, and tumor suppressors.
Cell cycle phases
Labile cells what and examples
Never go to G0, divide rapidly with a short G1.
Bone marrow, gut epithelium, skin, hair follicles.
Cell cycle phases Stable cells what and examples
Enter G1 from G0 when stimulated.
Hepatocytes, lymphocytes.
Cell cycle phases
Permanent cells what and examples
Remain in G0, regenerate from stem cells.
Never go to G0, divide rapidly with a short G1.
Cell cycle phases shortest phase
Mitosis
Posttranslational modifications Proteasomal degradation
Attachment of ubiquitin to defective proteins to tag them for breakdown.
Posttranslational modifications Covalent alterations
Phosphorylation, glycosylation, and hydroxylation.
Plasma membrane composition with %’s
Asymmetric fluid bilayer. Contains cholesterol (~50%), phospholipids (~50%), sphingolipids, glycolipids, and proteins.
Ouabain mech
inhibits Na+-K+ATPase by binding to K+ site.
Na+-K+ATPase location and orientation
Na+-K+ATPase is located in the plasma membrane
with ATP site on cytoplasmic side. For each ATP consumed, 3 Na+ go out and 2 K+ come in.
Elastin what and where
Stretchy protein within lungs, large arteries, elastic ligaments.
Marfan’s syndrome is caused by a defect in?
fibrillin.
Elastin wrt diseases
Emphysema can be caused by excess elastase activity
