Biochemistry - Cellular Flashcards
What regulates the cell cycle phases?
cyclins, cyclin-depenent kinases (CDKs), and tumor suppressors
What is the shortest phase of the cell cycle?
mitosis
What are cyclins?
regulatory proteins that control cell cycle events
phase specific
active CDKs
What is the role of a tumor suppressor? What are two examples of tumor suppressors?
- inhibit G1 to S progression in the cell cycle
2. p53 and hypophosphorylated RB protein
What happens if there is a mutation in a tumor suppressor gene?
Unrestrained cell division (e.g. Li-Fraumeni Syndrome)
What are the three cell types?
Give examples of each.
- 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)
What is the purpose of the rough endoplasmic reticulum?
synthesizes secretory proteins and N-linked oligosaccharide additions to many proteins
Where are peptide neurotransmitters for secretion from neurons made?
Nissl bodies
What cells are rich in RER?
mucus-secreting goblet cells and Ab-secreting plasma cells (makes lots of proteins!)
What is the purpose of the smooth ER? How is the SER different from the rough ER?
steroid synthesis and detoxification of drugs and poisons
LACKS ribosomes
What cells are rich in SER?
hepatocytes (detoxification)
steroid-hormone producing cells of the adrenal cortex
What is the purpose of the Golgi body?
Distribution center for proteins and lipids from the ER to the vesicles and plasma membrane
What is the matching amino acid to…
- N-oligosaccharide
- O-oligosaccharide
- mannose-6-phosphate
- asparagine
- serine and threonine
- proteins for trafficking to lysosomes
What disease is related to cell trafficking?
I- Cell Disease (Inclusion Cell Disease)
What is the pathogenesis of I-Cell Disease?
inherited LYSOSOMAL STORAGE DISORDER
Defect in phosphotransferase –> failure of the Golgi to phosphorylate mannose residues on glycoproteins –> proteins secreted extracellularly rather than delivered to lysosomes
What are the symptoms of I- Cell Disease?
Coarse facial features
Clouded corneas
Restricted joint movement
High plasma levels of lysosomal enzymes
*Often fatal in childhood
What direction does COP I traffic proteins?
Golgi –> Golgi (retrograde)
Golgi –> ER
What direction does COP II traffic proteins?
Golgi –> Golgi (anterograde)
ER –> Golgi
What direction does clathrin traffic proteins?
trans-golgi –> lysosomes
plasma membrane –> endosomes
What is the purpose of a peroxisome?
catabolism of very long chain fatty acids, branched chain fatty acids, and amino acids
What is the purpose of a proteasome?
degradation of damaged or ubiquitin-tagged proteins
What disease is associated with a defect in ubiquitin-proteasome system?
Parkinson disease
What is the purpose of a microtubule? Where are they found?
MOVEMENT
Found in flagella, cilia, mitotic spindles, axonal trafficking, centrioles
Cyclindrical structure composed of helical array of heterodimers of alph and beta tubular
What are the molecular motor proteins and what direction do they move cargo towards?
Dynein - retrograde (+ –> -)
Kinesin - anterograde (- –> +)
What are cilia?
9 + 2 arrangement of microtubules
Axonemal dynein - ATPase links peripheral 9 doublets and causes bending of cilium by different sliding of doublets
What disease is associated with ciliary dyskinesia?
Kartagener Syndrome (Primary Ciliary Dyskinesia)
Immotile cilia d/t a dynein arm defect
Symptoms
male and female infertility d/t immotile sperm and dysfunctional fallopian tube cilia
Increased risk of ectopic pregnancy
Other risks: bronchiectasis, recurrent sinusitis, and situs inversus
What is the purpose of 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
What is the purpose of intermediate filaments?
STRUCTURE
Found in vimentin, desmin, cytokeratin, lamins, glial fibrillary acid proteins (GFAP), neurofilaments
Types of Immunohistochemical stains for intermediate filaments
Vimentin - Connective Tissue DesMin - Muscle Cytokeratin - Epithelial cells GFAP - NeuroGlia Neurofilaments - Neurons
Where is the sodium potassium pump located? How many sodium and potassium are moved across the membrane?
plasma membrane
3 Na+ move out and 2 K+ move in
What is the most abundant protein in the body?
collagen
What is the most common type of collagen?
Type I collagen
What tissue is made from Type I collagen?
Bone (made by osteoblasts) Skin Tendon Dentin Fascia Cornea Late wound repair
What disease is associated with Type I collagen deficiency?
Osteogenesis imperfecta type I
What tissue is made from Type II collagen?
Cartilage (including hyaline)
Vitreous body
Nucleus pulposus
What tissue is made from Type III collagen?
Reticulin - skin, BLOOD VESSELS, uterus, fetal tissue, granulation tissue
What disease is associated with Type III collagen deficiency?
Vascular type of Ehlers-Danlos Syndrome
What tissue is made from Type IV collagen?
Basement membrane
basal lamina
lens
What disease is associated with defective Type IV collagen or Ab attack?
Defective - Alport syndrome
Ab attack - Goodpasture Syndrome
What type of cells produce collagen?
fibroblasts
What are the 6 steps to collagen synthesis and structure?
INSIDE fibroblast
- Synthesis (RER) - collagen is ⅓ glycine
- Hydroxylation (RER) - hydroxylation of proline and lysine residues (requires vitamin C)
- Glycosylation (RER) - glycosylation and formation of pro collagen via hydrogen and disulfide bonds (triple helix of 3 collagen alpha chains)
- Exocytosis into extracellular matrix
OUTSIDE fibroblast
- Proteolytic processing - cleave disulfide-rich terrine regions of pro collagen –> now an insoluble tropocollagen
- Cross-linking - reinforcement of many staggered tropocollagen molecules by covalent lysine- hydroxylyxine cross-linkage to make COLLAGEN FIBRILS
A deficiency in Vitamin C will result in inhibition of what step of the collagen synthesis process?
Hydroxylation (RER) - Step 2
Osteogenesis imperfecta causes problems in what step of the collagen synthesis process?
Glycosylation - Step 3
Problems forming triple helix
Ehlers-Danlos is associated with what step of the collagen synthesis process?
Cross-linking - Step 6
What is the pathogenesis of osteogenesis imperfecta?
Genetic bone disorder (brittle bone disease) caused by a variety of gene defects that inhibit proper forming of the triple helix of collagen
What are symptoms of osteogenesis imperfecta?
Multiple fractures with minimal trauma (may occur during birth process)
Blue sclerae d/t translucency of the CT over the choroidal veins
Hearing loss (abnormal ossicles)
Dental imperfections d/t lack of dentin
What is the inheritance pattern of osteogenesis imperfecta?
AD
What is the pathogenesis of Ehlers-Danlos Syndrome (EDS)?
Defect Type III collagen synthesis
What are the symptoms of Ehlers-Danlos Syndrome?
hyper extensible skin
tendency to bleed (easy bruising)
Hypermobile joints
May be associated with joint dislocation, berry and aortic aneurysms, organ rupture
What is the inheritance pattern of Ehlers-Danlos Syndrome?
AD or AR
What is the most common type of EDS?
hypermobility type (joint instability)
Classical type of EDS is associated with what type of collagen?
Type V collagen
What type of EDS is associated with vascular and organ rupture?
Vascular type –> aneurysms
What is the pathogenesis of Menkes disease and what are the Sx of the disease?
Impaired copper absorption and transport –> decreased activity of lysol oxidase (copper is a necessary cofactor)
Sx: brittle, “kinky” hair, growth retardation, and hypotonia
What is the purpose of elastin and where is it found?
Stretchy protein w/in in skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava
What amino acids is elastin rich in?
proline and glycine
What enzyme breaks down elastin and what inhibits this enzyme?
Elastase breaks down elastin
This enzyme is inhibited by alpha1- antitrypsin
What is the pathogenesis of Marfan Syndome?
defect in fibrillin (a glycoprotein that forms a sheath around elastin)
What is the pathogenesis of emphysema d/t an enzyme deficiency?
A1AT deficiency –> excess elastase activity
What causes wrinkles?
decrease in collagen and elastin production
