Biochemistry-Cellular Flashcards
CDKs
Constitutive and inactive
Cyclin
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
Cell Types- Permanent
Remain in G0, regenerate from stem cells
Give an example of a permanent cell
Neurons, skeletal and cardiac muscle, RBC
Cell Types- Stable (quiescent)
Engter G1 from G0 when stimulated
Give an example of a stable (quiescent) cell
Hepatocytes and lymphocytes
Cell Type- Labile
Never go to G0, divide rapidly witha short G1. Most affected by chemotherapy
Give an example of a labile cell
Bone marrow, gut epithelium, skin, hair follicles, and germ cells
Cell Type- Rough endoplasmic reticulum
Site of synthesis of secretory (exported) proteins and of N-linked oligosaccharide addition to many proteins. Nissl bodies (RER in neurons)- synthesize peptide neurotransmitters for secretion. Free ribosomes- unattached to any membrane; site of synthesis of cytosolic and organellar proteins.
Give an example of a rough endoplasmic reticulum cells
Mucus-secreting goblet cells of the small intestine and antibody-secreting plasma cells are rich in RER
Cell Type- Smooth endoplasmic reticulum
Site of steroid synthesis and detoxification of drugs and poisons. Lack surface ribosomes
Give an example of a smooth endoplasmic reticulum cell
Liver hepatocytes and steroid hormone- producing cells of the adrenal cortex and gonads are rich in SER
The golgi apparatus adds N-oligosaccharides to what amino acid?
Asparagine
The golgi apparatus adds O-oligosaccharides to which amino acids?
Serine and Threonine
What compound is added to the proteins destined for destruction by the lysosome? (Added by the golgi apparatus)
mannos-6-phosphate
What is the function of endosomes?
They are sorting centers for material from outside the cell or from the Golgi, sending it to the lysosomes for destruction or back to the membrane/Golgi for further use.
What is I-cell disease (inclusion cell disease)?
It is an inherited lysosomal storage disorder caused by a defect in phophotransferase which decreases mannose-6-phosphate on glycoproteins. Proteins are secreted extracellularly as opposed to tagged for the lysosome.
What is the likely diagnosis for a patient born with coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes?
I-Cell Disease. Often fatal in childhood.
What is a signal recognition particle (SRP)?
Abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER. Absent or dysfunctional SRP leads to proteins accumulatinng in the cytosol.
What is COPI?
Retrograde trafficking of protein from Golgi to ER
What is COPII?
Anterograde trafficking of protein from ER to Golgi
What is Clathrin?
A vesicular trafficking protein that traffics proteins from golgi to lysosomes, plasma membrane and endosomes (receptor mediated endocytosis)
What are peroxisomes?
Membrane-enclosed organelle involved in catabolism of very -long-chain fatty acids, branched-chain fatty acid, and amino acids.
What are proteasomes?
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’s disease.
What are microtubules?
Cylindrical structure composed of a helical array of polymerized heterodimers of alpha- and beta-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.
What are molecular motor proteins?
Proteins that transport cellular cargo toward opposite ends of microtubule tracks
In which direction does dynein travel?
Retrograde to microtubule (+ to -)
In which direction does kinesin travel?
anterograde to microtubule (-to +)
Name the drugs that act on microtubules. (Hint: Microtubules Get Constructed Very Poorly)
Mebendazole (anti-helminthic) Griseofulvin (anti-fungal) Colchicine (anti-gout) Vincristine/Vinblastine (anti-cancer) Paclitaxel (anti-cancer)
Describe the arrangement of cilia.
9+2 arrangement
What is axonemal dynein?
An ATPase that links peripheral 9 doublets and causes bending of cilium by differential sliding of doublets
What causes Kartagener Syndrome (Primary ciliary dyskinesia)?
Immotile cilia due to a dynein arm defect
Are individuals with Kartagener syndrome fertile?
No. Males are infertile due to immotile sperm and females are immotile due to dysfunctional fallopian tube cilia with a increased risk of ectopic pregnancy.
What are common symptoms of Kartagener syndrome?
Bronchiectasis, recurrent sinusitis, and situs inversus
Describe actin and myosin
Muscle contraction, microbvilli, cytokinesis, adherens junctions. Actins are long, structural polymers, myosins are dimeric, ATP-driven motor proteins that move along actins.
Describe microtubules
Movement. Cilia, flagella, mitotic spindle, axonal trafficking, centrioles.
Describe intermediate filaments
Structure. Vimentin, desmin, cytokeratin, lamin, glial fibrillary acid proteins (GFAP), neurofilaments.
Describe plasma membrane composition
Asymmetric lipid bilayer. Contains cholesterol, phopholipids, sphingolipids, glycolipids, and proteins. Fungal membranes contain ergosterol.
Describe sodium-potassium pumps
Sodium-potassium ATPase is located int eh plasma membrane with ATP site on cytosolic side. For each ATP consumed, 3 sodiums go out and two potassiums come in
What does Ouabain do?
Inhibits sodium-potassium pump by binding to potassium site
What do cardiac glycosides do? (digoxin and digitoxin)
They directl inhibit the sodium-potassium ATPase, which leads to indirect inhibition of sodium/calcium exchange which leads to increase calcium in the cell and increased cardiac contractility.
What is collagen?
Most abundant protein in the human body. Extensibely modified by posttranslational modification. Organizes and strengthens extracellular matrix
Where is type I collagen found?
Most common (90%)- Bone, Skin, Tendon, dentin, fascia, cornea, late wound repair
Where is type II collagen found?
Cartilage (including hyaline), vitreous body, nucleus pulposus.
Where is type III collagen found?
Reticulin-skin, blood vessels, uterus, fetal tissue, granulation tissue.
Where is type IV collagen found?
Basement membrane, basal lamina, lens
Where are collagen alpha chains synthesized?
Rough ER
Which amino acid is hydroxylated in collagen?
Proline and lysine. Requires vitamin C; deficiency is scurvy
Glycosylation and formation of procollagen via hydrogen and disulfide bonds creates what structure?
Triple helix
An error in glycosylation of pro-alpha-chain hydroxylysine residues results in what disorder
osteogenesis imperfecta
What processing transforms procollagen into insolube tropocollagen?
Proteolytic cleavage of disulfide-rich terminal regions
Cross-linking reinforces many staggered tropocollagen molecules by covalently cross-linking lysine-hydroxylysine to make collagen fibrils. A deficiency in cross-linking will cause what disorder?
Ehlers-Danlos
Describe elastin
It is a stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava. It is rich in proline and glycine, nonhydroxylated forms. tropoelastin with fibrillin scaffolding.
Cross-linking takes place extracellularly and gives elastin its elastic properties.
What enzyme breakes down elastin?
Elastase
What inhibits elastase?
alpha-antitrypsin
Defects in ubiquitin-proteasome system have been implicated in some cases of which disorder?
Parkinson disease
