Biochemistry-Molecular/Genetics Flashcards
What is rate limiting step of de novo purine nucleotide synthesis?
glutamine PRPP (5-phosphoribosyl-1-pyrophosphate) amidotransferase; inhibited by downstream products: IMP, GMP, AMP; cofactors: THF, glutamine, glycine, aspartate
Lesch-Nyhan Syndrome
HGPRT (converts hypoxanthine to IMP and guanine to GMP); tx w/ allopurinol (inhibits xanthine oxidase); X linked recessive
Severe combined T and B immunodeficiency
Adenosine deaminase deficiency; causes excess ATP/dATP and inhibits ribonucleotide reductase creating imbalance in nucleotide pool; autosomal recessive
Hereditary orotic aciduria
orotate phosphoribosyl transferase and/or OMP decarboxylase deficiency
Amino acids required for purine synthesis
glycine, aspartate, glutamate (used by glutamine PRPP amidotransferase)
converts ribonucleotides to deoxyribonucleotides
ribonucleotide reductase (inhibited by dATP, feedback)
inhibits dihydroorotate dehydrogenase
leflunomide
inhibit IMP dehydrogenase
mycophenolate, ribavirin
inhibits ribonucleotide reductase
hydroxyurea
inhibits de novo purine synthesis
6-MP and azathioprine (6MP prodrug)
thymidylate synthase
5-FU
inhibits dihydrofolate reductase in humans, bacteria, or protozoa
methotrexate (humans), trimethoprim (bacteria), pyrimethamine (protozoa)
DNA polymerase III
5’-3’ DNA synthesis; 3’-5’ exonuclease activity
DNA polymerase I
5’-3’ exonuclease activity, excises RNA primer (put down by primase)
endonuclease
nucleotide excision repair, base excision repair (glycosylase-AP site)
defective nucleotide excision repair
xeroderma pigmentosum–UV induced pryimidine dimers
defective mismatch repair
HNPCC
defective NHEJ
ataxia telengectasia
drugs that block DNA replication often have what modification?
3’-OH group to prevent addition of next nucleotide (DNA/RNA is synthesized 5’-3’
mRNA start codon
AUG (rarely GUG)
mRNA stop codons
UGA, UAA, UAG
inhibits RNA polymerase II
alpha-amantin (from death cap mushrooms); causes severe hepatotoxicity
cytoplasmic P bodies
mRNA quality control, contains exonucleases, decapping enzymes, microRNAs
anti smith antibodies
antibodies to spliceosomal snRNPs (highly specific for SLE)
anti U1 RNP
antibody to snRNP70–highly associated with mixed connective tissue disease
which end of tRNA carries amino acid? what sequence?
ALL tRNAs have a CCA on 3’ end that carries AAs
T-ARM of tRNA
contains thymidine/pseudourine/cytosine sequence necessary for tRNA ribosomal binding
D-ARM of tRNA
contains dihydrouracil residues necessary for tRNA recognition by the correct aminoacle-tRNA synthetase
Anticodon loop of tRNA
binds mRNA and is opposite the ACC/amino acid end
charging tRNA
aminoacyl-tRNA synthetase, requires ATP, 1 per amino acid matchmaker; requires D-arm of ATP for correct binding
tRNA translocation/activation
requires GTP/ATP respectively
course facial features, clouded corneas, restricted joint movement, high plasma levels of lysosomal enzymes
I-cell disease: inherited lysosomal storage disorder, defect in phosphotransferase, failure of golgi to phosphorylate mannose residues–>proteins delivered extracellularly instead of to lysosomes
What specifics does the Golgi modify?
modifies N-oligosaccharides on asparagine, adds O-oligosaccharides on serine/threonine, adds mannose-6-phosphate to proteins for lysosomal trafficking
traffics protein from ribosome to RER
signal recognition particle (SRP); ribonucleoprotein; when deficient–>proteins accumulate in cytosol
retrograde trafficking
COP1
anterograde trafficking
COP2
trans-golgi trafficking
clathrin
vimentin
connective tissue
desmin
muscle
cytokeratin
epithelial cells
GFAP
neuroglial cells
neurofilaments
neurons
Type 1 Collagen; disease?
Bone, skin, tendon, dentin, fascia, cornea, late wound repair; osteogenesis imperfecta type I
Type 2 collagen
cartilage (including hyaline); vitreous body, nucleus puplosus
Type 3 collagen, disease?
reticulin–skin, blood vessels, uterus, fetal tissue, granulation tissue–Ehler Danlos vascular type
Type 4 collagen; diseases?
basement membrane, basal lamina, lens; alport syndrome, goodpasture syndrome
which step of collagen synthesis is defective in osteogenesis imperfect?
Glycosylation step; formation of procollagen via hydrogen and disulfide bonds to form triple helix of procollagen
which step of collagen synthesis is defective in Ehler Danlos?
Cross linking step; Cu2+ containing lysyl oxidase; final step to make collagen fibrils
multiple fractures with minimal trauma occurring during birth process
Osteogenesis imperfecta–autosomal dominant with decreased production of otherwise normal type I collagen; blue sclerae, hearing loss, dental imperfections
brittle/kinky hair, growth retardation, low muscle tone as child
Menkes disease–impaired copper absorption and transport–decreased activity of lysyl oxidase; problems crosslinking
hyperphagia, obesity, intellectual disability, hypogonadism, hypotonia
Prader Willi syndrome; maternal imprinting (paternal gene is deleted); chromosome 15
inappropriate laughter, seizures, ataxia, severe intellectual disability
Angelman Syndrome; paternal imprinting (materal gene deleted); chromosome 15
Example of x-linked dominant disorder
hypophosphatemic rickets (increased phosphate wasting at PCT)
myopathy, lactic acidosis and CNS disease
mitochondrial myopathy; failure in oxidative phosphorylation; muscle biopsy shows ragged red fibers; mitochondrial inheritance
ADPKD
autsomal dominant; PKD1 (chromosome 16); PKD2 (chromosome 4)
FAP
autosomal dominant; APC (chromosome 5; polyp has 5 letters)
telangectasia, recurrent nosebleeds, skin discoloration, AVMs, gi bleeding, hematuria
Hereditary hemorrhagic telangectasia, autosomal dominant, aka Osler Weber Rendu syndrome
Huntington disease
AD; chromosome 4; CAG repeats
cystic medial necrosis of aorta; floppy mitral valve, lens subluxation typically upward and temporally
Marfan syndrome–fibrillin 1 defect (sheath for elastin)
MEN syndromes inheritance pattern
autosomal dominant
cafe au lait spots and cutaneous neurofibromas
NF1, AD, chromosome 17
bilateral acoustic schwannomas, juvenile cataacts, meningiomas, ependymomas
NF2, AD, chromosome 22
numerous benign hamartomas
tuberous sclerosis–AD, incomplete penetrance, variable expression
retinal, medullary, cerebellar angiomas, bilateral renal cell carcinoma
von hippel lindau disease; AD, chromosome 3
cystic fibrosis
CFTR gene on chromosome 7; AR
Some autosomal recessive diseases:
albinism, ARPKD, CF, glycogen storage diseases, hemochromatosis and Wilsons, Kartagener, mucopolysaccharidoses (except Hunter syndrome X linked R); PKU, sickle cell, sphingolipidoses (except Fabry XLR w/ incomplete penetrance), thalassemias
X-linked Recessive disorders
Be Wise Fools GOLD Heeds Silly HOpe: bruton, wiskott-aldrich, fabry, G6PD, ocular albinism, Lesch Nyhan, Duchenne (and becker), hemophilia A/B, Hunter syndrome, OTC deficiency
myotonia, muscle wasting, frontal balding, cataracts, testicular atrophy, arrhythmia
Myotonic type 1 dystrophy–CTG repeats in CMPK gene
post-pubertal macroorchidism, long face with large jaw, large everted ears, autism, mitral valve prolapse
Fragile X syndrome–X-linked CGG repeats in FMR1 gene
What are the trinucleotide repeats in common repeat disorders:
X-Girlfriends First Aid Helped Ace My Test: Fragile X–CGG; Friedrich’s ataxia–GAA; Huntington–CAG; Myotonic dystrophy–CTG
Imaging and lab findings in Down Syndrome
First trimester US: increased nuchal translucency, hypoplastic nasal bone; serum PAPP-A is decreased, free bHCG is elevated; Quad screen: decreased AFP and estriol; increased bHCG and inhibinA
Lab findings in Edwards syndrome
everything is down
US and Lab findings in Patau syndrome
everything is down, but increased nuchal translucency
microcephaly, moderate to severe intellectual disability, crying/mewing, epicanthal folds, cardiac abnormalities (VSD)
Cri du chat–microdeletion of short arm of chromosome 5 46XX/XY, 5p-)
elfin facies, intellectual disability, hypercalcemia, conversant, extremely friendly, cardiovascular problems
Williams Syndrome–microdeletion of long arm of chromosome 7
22qll deletion
Cleft palate, abnormal facies, thymic aplasia, cardiac defects, hypocalcemia (parathyroid aplasia)–defects in 3/4th branchial pouch formation–DiGeorge, velocardiofacial syndrome
