Cellular Biochemistry Flashcards
Cell Cycle Regulators
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 normlly inhibit G1-to-S progression; mutations in these genes result in unrestrained cell division
Mitosis phases
Prophase, metaphase, anaphase, and telophase.
Cell types: Permanent
Remain in G0, regenerate from stem cells
Neurons, skeletal, and cardiac muscle, RBCs
Cell types: Stable (quiescent)
Enter G1 from G0 when stimulated
Hepatocytes, lymphocytes
Cell types: Labile
Never go to G0, divide rapidly with a short G1. Most affected by chemotherapy.
Bone marrow, gut epithelium, skin, hair follicles, germ cells
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. Mucus secreting goblet cells of the SI and Ab secreting plasma cells are rich in RER Free ribosomes - unattached to any member; site of synthesis of systolic and organellar proteins
Smooth endoplasmic reticulum
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 SER
Golgi apparatus
Distribution center for proteins and lipids from the ER to vesicles and plasma membrane
I -cell Disease (inclusion cell-dz)
inherited lysosomal storage disease; defect in phosphotransferase -> failure of the golgi to phosphorylate mannose residues (i.e., decreases mannose-6-phosphate) on glycoproteins -> proteins are secreted extracellularly rather than delivered to lysosomes
Sxs: coarse facial features, clouded corneas, restricted joint movement, and high plasma levels of lysosomal enzymes.
Often fatal in childhood
Signal recognition particle (SRP)
Abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER
Absent or dysfunctional SRP -> proteins accumulate in the cytosol
Vesicular trafficking proteins: COPI
Golgi -> Golgi (retrograde); Golgi -> ER
Vesicular trafficking proteins: COPII
Golgi -> Golgi (anterograde); ER -> Golgi
Vesicular trafficking proteins: Clathrin
trans-Golgi -> lysosomes; plasma membrane -> endosome (receptor mediated endocytosis)
Peroxisome
membrane-enclosed organelle involved in the catabolism of very long chain FAs, branched chain FAs, and AAs
Proteasome
barrel-shaped protein complex that degrades damaged or ubiqiotin-tagged proteins. Defects in the ubiquitin-proteasome system have been implicated in some cases of Parkinson disease
Microtubule
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
Molecular motor proteins (Dynein and Kinesin)
Transport cellular cargo towards opposite ends of microtubules tracks
Dynein - retrograde (+ to -)
Kinesin - anterograde
Kartagener syndrome (Primary 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; increased risk of ectopic pregnancy.
Can cause bronchiectasis, recurrent sinusitis, and situs inversus
Actin and myosin
Muscle contraction.
ATP causes myosin to want to bind to actin. Myosin cannot bind to actin until tropomyosin has moved out of the way. It is moved out of the way when calcium enters and binds with troponin. At this point myosin binds to actin pulling the z-line towards the m-line and the sarcomere is shorter and contracted
Plasma membrane composition
Asymmetric lipid bilayer.
Contains cholesterol, phospholipids, sphingolipids, glycolipids, and proteins.
Fungal membranes contain ergosterol.
NA+-K+ pump: For each ATP consumes how many Na+ and K+ move and in what direction?
3 Na+go out
2 K+ go in
Collagen Type 1
M/c (90%) - BONE, skin, tendon, dentin, fascia, cornea, late wound repair
Type I: bONE
Collagen Type 2
CARTILAGE (including hyaline), vitreous body, nucleus polposus
Type II: carTWOlage
Collagen Type 3
RETICULIN - skin, BLOOD VESSELS, uterus, fetal tissue, granulation tissue
Vascular type of Ehlers-Danlos syndrome (ThreE D)
Collagen Type 4
BASEMENT MEMBRANE, basal lamina, lens
Defective in Alport syndrome; targeted by autoantibodies in goodpasture syndrome
Collagen is richest in which amino acid?
Glycine
What is required to hydroxylate proline and lysine?
Vitamin C (deficiency -> scurvy)
What is required to hydroxylate lysine (alone)?
Copper
Which phases of collagen synthesis occur inside the fibroblasts and which occur outside the fibroblasts?
Inside: 1. Synthesis, 2. Hydroxylation, 3. Gylcosylation, 4. Exocytosis (all within the RER)
Outside: 5. Proteolytic processing, 6. Cross-linking
Problems forming the triple helix in the glycosylation stage of collagen synthesis leads to what disease?
osteogenesis imperfecta
In the proteolytic processing stage of collagen synthesis what is being cleaved from procollagen? What is the new product after cleavage?
Disulfide-rich terminal regions are cleaved transforming procollagen into insoluble tropocollagen.
What are the steps of collagen synthesis?
- Synthesis (RER) - Translation of collagen alpha chains (preprocollagen) - usually gly-X-Y (proline or lysine)
- Hydroxylation (RER) - hydroxylation of specific proline and lysine residues
- Gylcosylation of pro-alpha-chain hydroxylysine residues and formation of procollegen via hydrogen and disulphide bonds (forms triple helix of 3 collagen alpha chains)
- Exocytosis - exocytosis of procollagen into extracellular space
- Proteolytic processing - Cleavage of disulfide rich 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 lysysl oxidase) to make collagen fibrils
Problems with the cross-linking stage of collagen synthesis leads to which disease?
Hint: Disease associated with Type III collagen
Ehlers-Danlos
Osteogenesis imperfecta
Genetic bone disorder (brittle bone dz) caused by gene defects
M/c form is autosomal dominant with decreased production of otherwise normal Type 1 collagen
Clinical features: multiple fractures with minimal trauma (birthing process), blue sclera, hearing loss (abnormal ossicles), dental imperfections
May be confused with child abuse
Ehlers-Danlos Syndrome
Faulty collagen synthesis causing hyperextensible skin, tendency to bleed (bruising), hypermobile joints Autosomal dominant or recessive. Maybe associated with joint dislocation, berry and aortic aneurysms, organ rupture. Hypermobility type (joint instability) - m/c Classical type (joint and skin problems) - mutation in type V collagen Vascular type (vascular and organ rupture) - def. type III collagen
Menkes dz
Connective tissue dz caused by impaired copper absorption and transport. Leads to decreased activity of lysysl oxidase (copper is a necessary cofactor). Results in brittle, “kinky” hair, growth retardation and hypotonia
Elastin
stretchy protein within skin, lungs, large arteries, elastic ligaments, vocal cords, ligamenta flava (connect vertebrae)
Rich in proline and glycine, nonhydroxylated forms
Tropoelastin with fibrillin scaffolding
Cross-linking takes place extracellularly and gives elastin its elastic properties
Broken down by elastase, which is normally inhibited by apha1-antitrypsin
Marfan syndrome
caused by a defect in fibrillin (glycoprotein that forms sheath around elastin)
Features of the disorder are most often found in the heart, blood vessels, bones, joints, and eyes. Some Marfan features – for example, aortic enlargement (expansion of the main blood vessel that carries blood away from the heart to the rest of the body) – can be life-threatening. The lungs, skin and nervous system may also be affected
Emphysema
can be caused by alpha1-antitrypsin deficiency, resulting in excess elastase activity.
