cellular biochem Flashcards
What does p53 do
induces p21 –> inhibits CDKs
- hypophosphorylation (activation of Rb)
- inhibition of G1-S progression
Li-Fraumeni syndrome
mutation in p53 tumor suppressor gene = unrestrained cell division
Growth factors
insulin, PDGF, EPO, EGF
all bind
tyrosine kinase receptors to transition cell from G1 to S phase
Permanent cells
neurons skeletal and cardiac muscle RBCs regenerate from stem cells remain in G0 phase
Stable (quiescent) cells
hepatocytes lymphocytes PCT periosteal cells enter G1 from G0 when stimulated
Labile cells
Bone marrow gut epithelium skin hair follicles germ cells never go into G0, divide rapidly w/short G1
Cells most affected in chemo
labile cells
RER in neurons are called
Nissl bodies
make peptide Its for secretion
2 cells rich in rough ER
- Mucus secreting goblet cells of small intestine
- antibody secreting plasma cells
site of steroid synthesis and detoxification of drugs/poisons
smooth ER
2 cells rich in smooth ER
- liver hepatocytes
- steroid hormone producing cells of adrenal cortex/gonads
Cell trafficking/distribution center for proteins and lipids from ER to vesicles and plasma membrane
golgi
The golgi modifies N-oligosaccharides on
asparagine
The golgi adds O-oligosaccharides on
serine and threonine
The golgi adds mannose-6-phosphate to proteins for trafficking to
lysosomes
sorting centers for material from outside cell or from golgi
Endosomes
sends to lysosomes for destruction or back to membrane/golgi for further use
inherited lysosomal storage disorder
defect in N-acetylglucoasaminyl-1-phosphotransferase
I-cell disease (inclusion cell disease/mucolipidosis type II)
Presentation of I-cell disease
- failure of golgi to phosphorylate mannose residues on glycoproteins
- proteins secreted extracellularly rather than delivered to lysosomes
- coarse facial features
- gingival hyperplasia
- clouded corneas
- restricted movements
- claw hand deformities
- kyphoscoliosis
- high plasma lysosomal enzymes
- fatal in childhood
accumulation of protein in cytosol
absent/dysfunctional signal recognition particle
what is a signal recognition particle
abundant in cytosol
ribonucleoprotein
what does SRP do
traffics polypeptide-ribosome complex from cytosol to RER
beta-ox
alpha-ox
catabolism of branched chain FA, AA, ethanol
makes cholesterol, bile acids, plasmalogens
peroxisomes
AR disorder of peroxisome biogenesis hypotonia seizures hepatomegaly early death
Zellweger syndrome
mutated PEX genes
AR disorder of alpha oxidation scaly skin ataxia cataracts/night blindness shortening of 4th toe epiphyseal dysplasia
Refsum disease phytanic acid not metabolized to pristanic acid
how to treat refsum disease
diet
plasmapheresis
XR
disorder of beta oxidation
Progressive disease that can lead to adrenal gland crisis, coma, death
Adrenoleukodystrophy
mutated ABCD1 gene
What do you get a build up of in Adrenoleukodystrophy
VLCFA in adrenal glands, white matter, testes
ubiquitin-proteasome system have been implicated in some cases of
Parkinson disease
type of filament involved in muscle contraction and cytokinesis
microfilaments
- actin
- microvilli
type of filament involved in maintaining cell structure
intermediate filaments
- vimentin
- desmin
- cytokeratin
- lamins
- GFAP
- neurofilaments
type of filament involved in movement and cell division
microtubules
- cilia
- flagella
- mitotic spindle
- axonal trafficking
- centrioles
Dynein
retrograde to microtubule ( + to -)
Kinesin
anterograde (- to +)
Drugs that act on microtubules
Mebendazole (anthelminthic) Griseofulvin (anti fungal) Colchicine Vincristine/Vinblastine Paclitaxel
what allows for coordinated ciliary movement
gap junctions
Kartagener’s syndrome can cause what in a woman
ectopic pregnancy
infertility
Kartagener’s syndrome can cause
bronchiectasis recurrent sinusitis chronic ear infection conductive hearing loss situs inversus
How to screen for Kartagener’s (AR)
decreased nasal nitric oxide
Problems forming triple helix during glycosylation of pro-alpha-chain hydroxylysine in the cytosol causes
osteogenesis imperfecta
Vitamin C deficiency affects
hydroxylation of specific proline and lysine residues for collagen synthesis in cytosol
what two processes of collagen synthesis happen extracellularly
proteolytic processing
cross-linking
what is collagen proteolytic processing
cleavage of disulfide rich terminal regions or procollagen —> insoluble tropocollagen
problems with proteolytic processing of collagen causes
Ehlers-Danlos
What is collagen cross-linking
reinforcement of many staggered tropocollagen molecules by covalent lysine-hydroxylysine cross-linking by copper-containing lysol oxidase to make collage fibrils
problems with collage cross-linking causes
Ehlers-Danlos
Menkes disease
MC genetic defect in osteogenesis imperfecta
COL1A1
COL1A2
Classical type (joint and skin) of Ehlers-Danlos genetic mutation
type V collagen
COL5A1
COL5A2
Vascular type Ehlers Danlos
type II pro collagen
COL3A1
Genetic defect in Menkes disease
defective Menkes protein
ATP7A
Brittle kinky hair
growth retardation
hypotonia
Menkes Disease
Menkes disease is caused by
impaired copper absorption and transport
decreased activity of lysol oxidase
defective collagen
MC type of Ehlers-Danlos
hyper mobility type
MC type of osteogenesis imperfects inherited usually
AD
decrease production of otherwise normal type I collagen
can have hearing loss (abnormal ossicles)
What is elastin
stretchy protein in
skin, lungs, large arteries, elastic ligaments, vocal cords, ligaments flava
elastin is rich in
NONhydroxylated proline, glycine, lysine
elastin is normally broken down by
elastase
elastase is inhibited by
alpha-1-antitrypsin
changes with aging
decreased dermal collagen and elastin
decreased collagen fibrils
cross linking stays the same
Subluxation of eyes in Marfans
upward and temporally (vs. down and in w/homocystinuria)
MCC of death in Marfans
dissection and HF
Marfan syndrome genetic mutation
AD
FBN1 gene on chr 15
defective fibrillin
MC presentation of Marfan’s
MVP and cystic degeneration of aorta
aortic aneurysm
