Biochemistry-Cellular Flashcards
Describe regulation of the cell cycle
Checkpoints control transitions between phases in the cel cycle. This process is regulated by cyclines, cyclin-dependent kinases (CDKs), and tumor suppressors.
What is included in M phase?
mitosis (prophase, prometaphase, metaphase, anaphase, and telophase) and cytokinesis
What are the phases of the cell cycle?
M - G1 - S - G2 -M
Note that CDKs are constitutive and active,
Cyclins are regulatory proteins that control cell cycle events; are ohase specific, and activate CDKs
Cyclin-CDK complexes phosphorylate other proteins to coordinate cell cycle progression
What normally inhibits G1 to S progression?
p53 and hypophosphorylated Rb (mutations in these genes can result in unrestrained cell growth (e.g. Li- Fraumeni syndrome)
What are the main cell types?
Permanent (remain in Go phase, regenerate from stem cell; neurons, skeletal and cardiac muscle; RBCs)
Stable (enter G1 when stimulated; hepatocytes, lymphocytes)
Labile (Never go to Go, divide rapidly with a short G1; most affected by chemo; bone marrow, gut epithelium, skin, germ cells hair)
What is the rough ER?
the site of synthesis of secretory (excreted) proteins and of N-linked oligosaccharide addition to many proteins
Nissl bodies (RER in neurons) synthesize peptide neurotransmitters for secretion
What does the smooth ER do?
site of steroid synthesis and detox of drugs and poisons (lacks surface ribosomes)
Liver hepatocytes and steroid hormone producing cells of the adrenal cortex and gonads are rich in SER
Describe cell trafficking
The golgi is the distribution center for proteins and lipids from the ER to the vesicles and plasma membrane. The golgi modified N-oligosacchardies on asparagine, adds O-oligosacchardies on serine and threonine, and adds mannose-6-phosphate to proteins for trafficking to lysosomes
Endosomes are the sorting centers for materials from outside the cells or from the SGolgi, sending it to lysosomes for destruction or back to the membrane/Golgi for further use
What is I disease?
(inclusion cell disease)- inherited lysosomal storage disorder caused by a defect in N-acetylglucosaminyl-1-phosphotransferase that results in failure of the Golgi to phosphorylate mannose residues (i.e. decreased mannose-6-phosphate) on glycoproteins. This results in proteins that are secreted extracellularly rather than delivered to lysosomes.
How does I disease present?
coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes
Often fatal in childhood
What is a signal recognition particle?
Abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER. Absent or dysfunctional SRP causes proteins to accumulate in the cytosol
What are some major vesicular trafficking proteins?
COP1: Golgi to golgi (retrograde) or cis-Golgi to ER
COP2: ER to cis-Golgi (anterograde)
Clathrin: trans-golgi to lysosomes and plasma membrane to endosomes (receptor mediated endocytosis)
What is the role of peroxisomes?
Membrane-enclosed organells involved in the catabolism of very-long-chain fatty acids, branched-chain FAs, and AAs
What is the role of proteasomes?
These are barrel-shaped protein complexes that degrade damaged or ubiquitin-tagged proteins (defects in this system have been implicated in Parkinson disease)
What are the main cytoskeleton components?
Microfilaments (actin; muscle contraction, cytokinesis)
Intermediate filaments (e.g. vimentin, GFAP, desmines, cytokeratin, lamins, neurofilaments; maintain cell structure)
Microtubules (e.g. cilia, flagella, mitotic spindle, neuronal trafficking; movement, and cell division)
What body part does a vimentin stain ID? Desmins? Cytokeratin?
Vimentin- Connective tissue
Desmin- Muscle
Cytokeratin- Epithelial cells
What body part does a GFAP stain ID? Neurofilaments?
GFAP- Neuroglia
Neurofilaments- neurons
Describe the structure of microtubules
cylindrical structure composed of a helical array of polymerized heterodimers of a- and b-tubulin. Each dimer has 2 GTP bound.
Microtubules are incorporated into flaggella, cilia, mitotic spindles
Anterograde transport along microtubules is accomplished via ______. Retrograde?
Anterograde- kinesin
Retro- dynein
What drugs act upon microtubules?
Microtubules Get Constructed Very Poorly
Mebendazole (antihelminthic)
Griseofulvin (antifungal)
Colchicine (antigout)
Vincristine/Vinblastine
Paclitaxel
What is the structure of cilia?
9+2 arrangement of microtubule doubles with axonemal dynein, an ATPase that links peripheral 9 doubles and causes bending of cilium by sliding
What is Kartagener syndrome (primary ciliary dyskinesia)?
immotile cilia due to a dynein arm defect resulting in male and female infertility due to immotile sperm and dysfunctional fallopian tube cilia.
Increased risk of ectopic pregnancy
Can also result in bronchiectasis, recurrent sinusitis, and situs inversus
What is the composition of the plasma membrane?
asymmetric lipid bilayer containing cholesterol, phospholipids, spingolipids, glucolipids, and proteins
NOTE: Fungal membranes contain ergosterol
Describe the NaKATPase
3Na+ go out of the cell (when the pump is phosphorylated), 2K+ go in (when the pump is dephosphorylated)
What drugs block the NaKATPase?
Ouabain inhibits by binding to the K+ sight
Cardiac glycosides (digoxin and digitoxin) directly inhibit, whihc leads to indirect inhibition of Na/Ca2+ exchange to increase intracellular Ca2+ leading to increased cardiac contractility
What are the types of collagen?
I-IV
Describe type I collagen
most common (90%)- found in bone (made by osteoblasts), skin, tendons, dentin, fascia, cornea, and is involved in late wound repair
Decreased production in osteogenesis imperfecta type I
Describe type II collagen
found in cartilage (including hyaline), vitreous body, and nucleus pulposus
Describe type III collagen
found in reticulin-skin, blood vessels, uterus, fetal tissue, and granulation tissue
Type III is deficient in the uncommon, vascular type of Ehlers-Danlos
Describe type IV collagen
Found in basement membrane, basal lamina, and the lens
defective in Alport syndrome, and targeted by Abs in Goodpasture syndrome
Describe the initial parts of collagen synthesis and structure
- Synthesis (RER)-translation of collagen a chains (preprocollagen)-usually Glu-X-Y (X and Y are proline or lysine). Glycine content best reflects collagen synthesis (collagen is 1/3 glycine)
2) Hydroxylation of specific proline and lysine residues (requires vitC; deficiency= scurvy)
Describe the parts 3 and 4 of collagen synthesis and structure
3) Glycosylation of pro-a-chain hydroxylysine residues and the formation of procollagen via hydrogen and disulfide bonds (triple helix of 3 collagen a chains); Problems forming triple helix= osteogenesis imperfecta
4) Exocytosis of procollagen from fibroblast into extracellular space
Describe the parts 5 and 6 of collagen synthesis and structure
5) Proteolytic processing-cleavage of disulfide rich terminal regions of procollagen, transforming it into insoluble tropocollagen
6) Cross-linking: Reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linkage (by copper-containing lysyl oxidase) to make collagen fibrils; problems with cross-linking= Ehlers-Danlos or Menkes disease
Describe osteogenesis imperfecta
Genetic bone disorder caused by defects in collagen processing. Manifests with:
mutliple fractures with minimal trauma
blue sclera due to the translucency of the CT over the choroidal veins
hearing loss (abnormal ossicles)
dental imperfections due to a lack of dentin
What is Ehlers Danlos syndrome?
Disease of faulty collagen syntheis causing hyperextensible skin, tendency to bleed, and hypermobile joints
There are multiple types and inheritance and severity may vary (can be AD or AR)
What are some types of Ehlers Danlos syndrome?
Hypermobility (most common)
Classical types (joint and skin problems)- caused by mutation in type V collagen
Vascular type (vascular and organ rupture)-deficient type III collagen
What is Menkes disease?
X-linked recessive CT disease caused by impaired copper absorption and transport due to a defective Menkes protein (ATP7a) leading to decreased activity of lysyl oxidase resulting in brittle, kinky hair, growth retardation, and hypotonia
What is elastin?
stretchy protein within skin, lungs, large, arteries, elastic ligaments, vocal cords, and ligamenta flava
What is the composition of elastin?
rich is nonhydroxylated proline, glycine, and lysine residues
Elastin is normally broken down by _______
elastase (which is inhibited by a1-antitrypsin
What causes Marfan syndrome?
defct in fibrillin, a glycoprotein that forms a sheath around elastin
What causes wrinkling of skin with age?
decreased collagen and elastin production
