cellular biochem and genetics Flashcards
M phase
mitosis and cytokinesis
shortest phase
CDK
constitutive
inactive
cyclins
phase specific
activate CDKs
cyclin-CDK complex
phosphorylate other proteins to coordinate cell cycle progression
must be activated and inactivated at appropriate times for cell cycle to progress
tumor supressors
p53
hyophosphorylated Rb
inhibit G1 -> S progression
mutated -> LiFraumeni syndrome
permanent cells
remain in G0
regenerate from stem cells
neurons, skeletal and cardiac mm
RBCs
stable/quiescent cells
enter G1 when stimulated
hepatocytes
lymphocytes
labile cells
never go to G0
divide rapdily w/short G1
most affected by chemo
skin, hair, bone marrow, GI lining, germ cells
RER
synthesis of secretory proteins
Nissl bodeis (RER in neurons) synthesis NTs
mucus-secreting goblet cells and AB secreting plasma cells have a lot
Free ribosomes
cytosolic and organellar proteins
SER
site of steroid synthesis and detox of drugs and poisons
lack surface ribosomes
liver hepatocytes and steroid hormone producing cells
signal recognition particle (SRP)
abundant, cytosolic ribonucleoprotein that traffics proteins from the ribosome to the RER
if absent proteins accumulate in cytosole
vesicular trafficking proteins
COPI, COPII, Clathrin
COPI
golgi -> golgi (retrograde)
cisGolgi -> ER
COPII
ER -> cisGolgi (anterograde)
clathrin
transGolgi -> lysosomes
plasma membrane -> endosomes
peroxisome
catabolism of very long chain fatty acids
brr-chain fatty acids
aa
proteasome
barrel-shaped protein complex, degrades damaged or ubiquinated proteins
defects implicated in parkinsons
I-cell disease
inclusion cell disease
inherited lysosomal storage disorder
defect in N-acetylglucosaminyl-1-phosphotransferase -> failure of goligi to phosphorylate mannose -> proteins excreted extraceullularly rather then into lysosomes
clinical features of I-cell disease
coarse facial features clouded corneas restricted joint mvmt high plasma levels of lysosomal enzymes often fatal in childhood
microfiiliments
mm crontraction
cytokinesis
actin
intermediate filaments
cell structure vimentin desmin cytokeratin lamins GFAP neurofilaments
microtubules
mvmt, cell division cilia flagella mitotic spindle axonal trafficking centrioles
vimentin stain
CT
desMin stain
mm
cytokeratin
epi
GFAP
neuroGlia
neurofiliaments
neurons
microtubules anatomy
polymerized heterodimers of alpha and beta tubulin
each dimer has 2 GTP bound
dynein
retrograde (+ -> -)
kinesin
anterograde (- -> +)
drugs that act on microtubules
Microtubules Get Constructed Very Poorly Mebendazole (anithelminthie) Griseofulvin (antifungal) Colchicine (antigout) Vincristine/Vinblastine (antiCA) Paclitaxel (antiCA)
Cilia structure
9+2 arrangement of microtubule droplets
kartagener syndrom
aka primary ciliary dyskinesia immotile cilia d/t dynein arm defect male and female infertility increased risk for ectopic brochiectasis, recurrent sinusitis situs inversus ADPCKD
oubain
inhbits NA/K ATPase by binding K site
cardiac glycosies
digoxin/digitoxin
directly inhibit Na/K ATPase -> indirect inhbition of Na/Ca exchange -> increased Ca -> increased contractility
Collagen
Be So Totally Cool, Read Books
I- Bone, skin, tendon (late wound repair)
II- Cartilage (vitreous body, nucleus propulsus)
III- Reticulin, skin, blood vessels, granulation tissue
IV- BM, basal lamina, lens (type IV under the floor-BM)
decreased type I collagen production
osteogenesis imperfecta type I
vascular type of Ethers Danlos
uncommon
type III deficient
alport syndrome
type IV defective
collagen synthesis inside fibroblast
synthesis in RER -> preprocollagen
hydroxylation in RER (requires Vit C)
glycosylation in RER -> precollagen (osteogenesis imperfecta)
exocytosis
collagen synthesis outside fibroblast
proteolytic- cleavage of disulfide rich terminal regions -> tropocollagen
cross linking -> requires Cu (Menkes disease, ED)
osteogenesis imperfecta
brittle bone disease
most common AD
decreased production of normal type I collagen
fracture, blue sclera, hearing loss, fental imperfections
Ethers Danlos
AD or AR
associated w/joint dislocaton, berry/aortic aneurysms, organ rupture
types of ED
- hypermobility type, most common, joint instability
- classical type mutation in type V collagen, joint and skin
- vascular type deficient type III collagen, vascular and organ rupture
menkes disease
XR impaired Cu absorption and transport defective menkes protein (ATP7A) decreased lysyl oxidase activity brittle, kinky hair, growth retardation, hypotonia
Elastin
rick in nonhydroxylated proline, glycine, and lysine
broken down by elastase which is normally inhibited by alpha 1 anti-trypsin
marfans
misfolded fibrillin-1
glycoprotein that forms sheath around elastin
Blotting procedures
SNoW DRoP
Southern = DNA
Northern = RNA
Western = protein
locus heterogenity
mutations at different loci can produce same phenotype
albinism
allelic heterogenity
different mutations in same locus produce same phenotype
beta thalassemia
heteroplasmy
presence of both normal and mutated mtDNA
variable expression in mitochondrially inherited diseases
prader-willi
maternal imprinting (moms usually silent) Paternal deleted
hyperphagia, obesity, retardation. hypogonadism, and hypotonia
25% d/t maternal uniparental disomy
angleman
paternal impriting (dads usually silent) maternal deleted inappropriate laughter, seizures, ataxia, severe intellecutual disability 5% d/t paternal uniparental disomy
mitochondrial myopathies
rare disorder often presents w/myopathy, lactic acidosis, and CNS disease
secondary to failure in ox phos
mm Bx- ragged red fibers
ADPKD
85% d/t mutation in PKD1, chrom 16 (16 letters in polycystic kidney)
15% d/t mutation in PKD2 (chrom 4)
familial adenomatous polyposis inheritance?
AD
familial hypercholesterolemia inheritance?
AD
albinism inheritance?
AR
hereditary hemorrhagic telangiectasia inheritance?
AD
cystic fibrosis inheritance?
AR
glycogen storage diseases inheritance?
AR
hemochromatosis inheritance?
AR
hereditary sphrocytosis inheritance?
AD
Huntingtons inheritance?
AD
Kartagener syndrome inheritance?
AR
LiFraumeni syndrome inheritance?
AD
Marfan’s syndrome inheritance?
AD
multiple endocrine neoplasia (MEN) inheritance?
AD
NF1 inheritance?
AD
mucopolusaccharidoses inheritance?
AR
phenylketonuria inheritance?
AR
NF2 inheritance?
AD
sickle cell inheritance?
AR
sphingolipidoses inheritance?
AR (except Fabry’s)
Tuberous sclerosis inheritance?
AD
thalasemias inheritance?
AR
VHL disease inheritance?
AD
Wilson’s disease inheritance?
AR
Familial adenomatous polyposis
AD
colon becomes covered w/adenomatous polyps after puberty
progresses to colon CA unless colon resected
mutations on chrom 5 (5 letters in polyp) APC gene
familial hypercholesterolemia
AD elevated LDL d/t defective or absent LDL Rs tendon xanthomas (classically in achilles), corneal arcus
hereditary hemorrhagic telangiectadsia
AD
aka Osler-Weber-Rendu sndrome
telangiectasia, epistaxis, skin disocoloration, AVMs, GI bleds, hematuria
hereditary spheocytsis
AD spheroid RBCs, d/t spectin or ankyrin defect hemolytic ane ia increased MCHC, RDW Tx splenectomy
huntingtons
AD
increased DA, decreased GABA and ACh
gene on chrom 4 (hunting For 4 food)
CAG repeats, anticipation
Li-Fraumeni syndrome
AD
mutated TP53 -> multiple CAs at young age
aka SBLA CA syndrome b/c get sarcomas, breast, leukemia, and adrenal gland CA)
Marfan’s
AD
FBN1 gene mutation on chrom 15 -> defective fibrillin-1 (scaffold for elastin)
tall w/long extremities, pectus excavatum, hypermobile joints, arachnodactyl
cystic medial necrosis of aorta -> aortic aneurysm
Floppy mitral valve
subluxation of lenses
MEN 1
AD pancreatic (gastinomas, insulinomas) pituitary parathyroid MEN1 gene
MEN 2A
AD parathyroid pheochromocytoma thyroid RET gene
MEN 2B
AD pheochromocytoma thyroid mucosal neuromas marfanoid body habitus RET gene
NF1
AD, 100% penetrance, variable expression aka von Recklinghausen cafe-au-laits spots cutaneous neurofibromas optic gliomas pherochromocytomas Lisch nodules (pigmented iris hamartomas) NF1 gene on chrom 17 (17 letters in von Recklinghausen)
NF2
AD b/l acoustic schwannomas juvenile cataracts mengingiomas ependymomas NF2 gene on chrom 22
Tuberous sclerosis
Dx Triad: -Angiofibromas on face -Metal delays -Seizures a lot get cardiac rhadomyomas TSC1- hamertin TSC2- tuberin Ash leaf patch-shine woodslamp (UVA) -> fluoresces AD, incomplete penetrance, variable expression
VHL
numerous tumors, both benign and malignant
deletion of VHL gene on chrom 3
CF
CFTR on chrom 7
most common mutation -> misfolded protein -> decreased CL and H20 secretion
N-acetylcystein loosen mucus plugs
x-linked recessive disorders
Be Wise Fool's GOLD Heeds Silly HOpe Bruton agammaglobulinemia Wischott-aldrich syndrome Fabry's G6PD deficiency Ocular albinism Lesch-Nyhan syndrome Duchenne and becker mm dystrophy Hunter Syndrome Hemophillia A and B Ornithine transcarbamylase deficieny
Duchenne
x-linked d/t frameshift
truncated dystrophin
weakness begins in pelvic girdle mm and progresses superiorly
psuedohypertrophy of calf mm d/t fibrofatty replacement of mm
Gower maneuver to stand
waddling gait
onset
Becker
x-linked d/t non-frameshift insertions
partially functional
less severe then duchennes
onset in adolescene or early adulthood
mytonic mm dystrophy type 1
AD
CTG repeat in DMPK gene
myotonia, mm wasting, cataracts, testicular atrophy, frontal balding, arrhythmia
My Tonia, My Testicles, My Toupee, My Ticker
Fragile X-syndrome
x-linked, CGG repeat
affecting methylation and expression of FMR1 gene
2nd MCC of genetic intellectual disability (downs first)
post-pubertal macroorchidism
long face w/large jaw
large ecerted ears
autism
MV prolapse
Fragile X = eXtra large testes, jaw, and ears
trinucleotide repeat expansions
Try hunting for my fried eggs (X) huntingtons myotonic dystropy friedreich ataxia fragile X syndrome
down syndrome associations
gap btwn 1st 2 toes duodenal atresia hirschsprugs congenital heart disease (ASD) Brushfield spots early onset alxhemiers ALL and AML
down syndrome 1st trimester ultrasound
increased nuchal translucency and hypoplastic nasal bone
serum PAPP-A is decreased
free B-hCG increased
down syndrome 2nd trimester quad screen
decreaed alpha-fetoprotein
increased beta-hCG
decreased estriol
increased inhibin A
Edwards syndrome
trisomy 18 severe intellectual disability rocker-bottom feet low-set ears celnced hands w/overlapping fingers prominent occiput congenital heart disease death w/in 1 yr
edwards 1st triemster
PAPP-A and free beta-hCG decreased
edwards quad screen
decreased alpha-fetoprotein
decreased beta-hCG
decreased estriol
decreased or normal inhibin A
Patau syndrome
severe intellectual disability rocker bottom feet microphthalmia microencephaly cleft lip/palate holoprosencephaly polydactyly congenital heart disease cutis aplasia death w/in 1 yr
patau first trimester
decreased beta-hCG
decreased PAPP-A
increased nuchal translucency
Cri-du-Chat syndrome
congenital microdeletion of short arm of chrom 5 microcephaly
moderate to severe intellectual disabiliyt
high pitched crying/mewing
epicanthal folds
VSD
williams syndrome
microdeletion of long arm of chrom 7 distinctive elfin facies intellectual disability hypercalcemia well developed verbal skills, extreme friendliness w/strangers CV problems
DiGeorge
22q11 deletions CATCH-22 Cleft palate abnormal facies thymic aplasia cleft palate hypocalcemia (secondary to parathyroid aplasia) velocardiofacial syndrome- only palate, facial, and cardiac
