Random Flashcards
Irinotecan/topotecan inhibit which topoisomerase?
1
Etoposide/teniposide inhibit which topoisomerase
2 (dna gyrase)
Which DNA polymerase degrades the RNA primer in prokaryotes
DNA polymerase I
what is a nonsense mutation
mutation resulting in stop codon (UAG, UAA, UGA)
Duchenne MD, Tay-Sachs are what class of genetic mutation
Frameshift
Xeroderma pigmentosum is a defect in?
nucleotide excision repair; pyrimidine dimers caused by UV exposure. Repair should occur in G1 phase
What process is defective in Lynch syndrome?
Mismatch repair
What process is defective in ataxia telangiectasia?
nonhomologous end joining
Homologous recombination is defective in which two cancer mutations/syndromes
BRCA1 (breast/ovarian), and in Fanconi Anemia
Capping of 5’end, polyadenylation of 3’ end, splicing out of introns all occurs in?
the nucleus
capped, tailed, spliced transcript is called?
mRNA
RNA polymerase I (eukaryotes) makes what type of RNA
rRNA; only in nucleolus
RNA polymerase II (eukaryotes) makes what types of mRNA
mRNA, snRNA
RNA polymerase III (eukaryotes) makes what types of RNA?
5S rRNA, tRNA
alpha-amanitin, from amanita phalloides death cap muschroom, inhibits which eukaryotic RNA polymerase?
RNA polymerase II
What does the RNA polymerase in prokaryotes make
all 3 kinds of RNA
Where is the CCA sequence on tRNA and what does it carry?
3’ end of tRNA; Can Carry Amino acids
T arm of tRNA purpose
tethers tRNA molecule to ribosome
What does aminoacyl-tRNA synthetase do?
charges tRNA w/ an amino acid at the 3’ CCA region
What does IF2 do to tRNA?
pairs it with the codon on the mRNA
How do p53, p21, CDKs, and Rb interact to inhibit the G1S cell cycle progression
p53 induces p21, which inhibits CDKs–> hypophosphorylation (activation) of Rb–> inhibition of G1S progression
What is the site of synthesis of the N-linked oligosaccharide and secretory (exported) proteins?
Rough ER
What modifies N-oligosaccharides on asparagine and adds O-oligosaccharides on serine and threonine? Also adds mannose-6-phosphate to proteins for trafficking to lysosomes
Golgi
I-cell disease is a defect in N-acetylglucosaminyl-1-phosphotransferase, which leads to failure of golgi to phosphorylate mannose residues on glycoproteins, what happens to these proteins?
they are secreted extracellulary rather than delivered to lysosomes.
Zellweger syndrome is an autosomal recessive disorder of peroxisome biogenesis due to what mutation?
PEX gene
Refsum disease is an autosomal recessive disorder of what? What are some findings related to the skin, eyes, and the fourth fucking toe?
Alpha-oxidation in peroxisomes—>phytanic acid not metabolized to pristanic acid. Scaly skin, ataxia, cataracts/night blindness, shortening of 4th toe, epiphyseal dysplasia.
Adrenoleukodystrophy is an X-Linked disorder of beta oxidation and subsequent buildup of VLCFAs in adrenal glands, white matter of brain, and testes, due to what mutation?
ABCD1
A decreased nasal nitric acid oxide is a positive screening in what two disorders?
VERY low in primary ciliary dyskinesia
Low in Cystif Fibrosis as well
Bone, skin, tendon, dentin, fascia, cornea are what type of collagen?
Type 1; which is decreased in osteogenesis imperfecta
Cartilage including hyaline, viteous body, and nucleus pulposus is what type of cartilage
Type 2
Type III collagen found in?
Reticulun—skin, blood vessels, granulation tissue
The lens/ basement membrane are what type of collagen
Type IV
Where does hydroxylation of proline/lysine, which requires Vitamin C, take place? (Collagen synthesis)
Rough ER
After glycosylation of pro-a-chain hydroxylysine residues, the triple helix forms due to hydrogen and disulfide bonds. This makes procollagen. A defect in this process results in what disease
Osteogenesis imperfecta; a problem w/ the secondary structure i.e. forming the triple helix
Problems w/ cleaving the disulfide rich terminal regions of procollagen into insoluble tropocollagen results in which disease? This occurs in the extracellular space
Ehlers-Danlos syndrome
Reinforcement of tropocollagen by covalent lysine-hydroxylysine cross-linkage by copper containing lysyl oxidase to make collagen fibrils results in which two diseases?
Ehlers Danlos, and Menkes disease
What disease is characterized by a decreased production of otherwise normal type I collagen? This disease can’t BITE
Bones=multiple fractures
I (eye)= blue sclerae
Teeth= dental imperfections
Ear= hearing loss due to abnormal ossicles
Osteogeneis imperfecta
What type of Ehlers Danlos is the most common type?
What type is a mutation in type V collagen?
What type is a mutation in type III procollagen?
Hypermobility type most common
Classical type is type V collagen
Vascular type is type III collagen
Brittle, kinky hair, growth retardation, hypotonia, ATP7A mutation
Menkes disease
FBN1 mutation on chromosome 15
Marfan
What do you use PCR for
Amplify a desired fragment of DNA*
What is the reverse transcriptase PCR?
Detects and quantifies mRNA levels using reverese transcriptase to create a complementary DNA template that is amplified via standard PCR procedure
SNoW DRoP for blotting procedures
Southern= DNA Northern= RNA Western= Protein
Why is the right lower quadrant empty in flow cytometry
All CD8 expressing cells also express CD3
a1-antitrypsin has MM normal, MS, SS, MZ, SZ, ZZ in order of increasing severity of lost AAT production. What genetic term is this a good example of
Codominance; both alleles contribute to phenotype
Loss of heterozygosity
If a patient inherits or develops a mutation in tumor suppressor gene, the complementary allele must be deleted/mutated before cancer develops. i.e. retinoblastoma, lynch syndrome (HNPCC), Li-Faumeni (germline tp53 mutation)
Pleiotropy
One gene contributes to multiple phenotypic effects such as PKU has light skin, mental retardation, musty body odor
Dominant negative
A heterozygote produces a nonfunctional altered protein that alsoprevents the normal gene product from functioning
Unilateral cafe au lait, polyostotic fibrous dysplasia (bone replaced by collagen and fibroblasts) and at least one endocrinopathy (eg precocious puberty) due to somatic activating mutation of the Gs protein GNAS
Mccune albright syndrome
Somatic mosaicism is a mutation that happens before or after fertilization?
After fertilization
Mutations at different loci produce similar phenotype?
Mutations in the same loci produce similar phenotype?
Locus heterogeneity is mutations at different loci
Allelic heterogeneity is different mutations in same locus
Presence of both normal and mutated mtDNA resulting in variable expression in mitochondrially inherited disease
Heteroplasmy
What are the equations for Hardy-Weinberg
p^2 + 2pq + q^2 =1
p + q = 1
p^2 is the frequency of homozygosity for allele A
q^2 is frequency of homozygosity for allele a
2pq is frequency of heterozygosity (carrier frequency if it is an autosomal recessive disease)
*The frequency of an X-linked recessive disease in males is q and in females it is q^2
Hypophasphatemic rickets, fragile X, alport syndrome all have what type of inheritance pattern
X-linked DOMINANT
Mothers transmit to 50% of daughters and sons; fathers transmit to all daughters but no sons?
X-linked Dominant
Secretes Cl- in lungs and Gi tract but reabsorbs Cl- in sweat glands
CFTR, normal
What agent used to induce sweat for CFTR mutation testing
Pilocarpine
What fluid balance status is most likely to present w/ a cystic fibrosis patient?
Contraction alkalosis and hypokalemia: ecf effects analogous to a patient taking a loop diuretic because of ECF H20/Na losses via sweating and concomitant renal K/H wasting
What is the newborn screening for CF?
Increased immunoreactive trypsinogen
Reticulonodular pattern on cxr
Bronchiectasis
What is lumacaftor and what is its MOA
CFTR phe508 deletion drug that corrects misfolded proteins and improves their transport to cell surface
What is ivacaftor and what is its moa
CFTR Phe508 deletion that opens Cl- channels and improves chlroide transport
What is an X-linked disorder due to a frameshift deletion that causes a truncated or absent dystrophin protein
Duchenne. Dystrophin protein helps anchor muscle fibers by connecting intracellular cytoskeleton (actin) to the transmembrane proteins alpha and beta dystroglycan, which are connected to the ECM. Loss of dystrophin causes myonecrosis
What lab values are up in a Duchenne MD patient
CK and aldolase
MCCOD in duchenne muscular dystrophy
Dilated cardiomyopahty
X-linked disorder due to NON-frameshift deletion resulting in partially functioning dystrophin protein
Becker
CTG expansion in DMPK leads to an abnormal expression of myotonin protein kinase. Which disease and what are the effects seen
Myotonic type 1 muscular dystrophy. Cataracts, Toupee, Gonadal atrophy
MECP2 de novo mutation on X chromosome with stereotyped hand-wringing, ataxia, failure to thrive
Rett syndrome
CGG expansion that occurs during oogenesis in the FMR1 gene, resulting in hypermethylation and decreased expression. X-linked DOMINANT disorder
Fragile X
GAA repeat
Friedreich ataxia
CAG repeat
Huntington. Caudate has decreased ACh and GABA
Increased hCG and inhibin
Down syndrome
Trisomy 13
Patau
Trisomy 18
Edward
In 1st trimester screening, B-hCG, and PAPP-A are decreased in trisomy 13,18, and 21 except for which exception?
beta-hcg of trisomy 21 is increased in first trimester screening
In 2nd trimester, what is findings for b-hcg, inhibin a, estriol, and AFP for trisomy 21
B-hcg and inhibin a are increased, estriol and afp are decreased
What are the 2nd trimester screening results for trisomies 18, 13 in regards to b-hcg, inhibin a, estriol, and AFP?
In trisomy 18 they are all down, except inhibin A might be normal
In trisomy 13 everything is unchanged
Elfin facies, hypercalcemia, supravalvular aortic stenosis
Williams syndrome: long arm of chr 7 deletion, deleted region includes elastin
What vitamin is used to treat measles and APL?
Vitamin a
High output cardiac failure due to thiamine deficiency
Wet beriberi (dilated cardiomyopathy)
What activity will increase once thiamine is given to a thiamine deficient patient?
Diagnosis is made by increased RBC transketolase activity after B1 administration
Corneal vascularization, Cheilosis
B2 (riboflavin) deficiency
B3 (niacin) is a derivative of ?
Tryptophan
The facial flushing produced by excess niacin is not induced by histamines but by? How can this be avoided?
Induced by prostaglandins, NOT histamine. Take the shit with aspirin to prevent
B vitamin needed for transamination decarboxylation reactions, synthesis of heme, and neurotransmitters
B6
When do you give someone folate before and during pregnancy
1 month before and for the entire 9 months
What is an ancillary treatment for methemoglobinemia
Vitamin C, works by reducing Fe3 to Fe2
Main treatment is methylene blue
An excess of which vitamin can make iron toxicity worse in predisposed patients
Vitamin C because it increases dietary iron absorption
Tocopherol and tocotrienol
Vitamin e
Dysgeuisia (taste distortion), anosmia, acrodermatitis enteropathica
Zinc deficiency
Marasmus
Malnutrition due to caloric deficit, not protein like in Kwashiokor.
Severe galactosemia enzyme
Galactose-1-phosphate uridyltransferase
Galactose-1-phosphate to Glucose-1-phosphate
Galactose-1-phosphate uridyltransferase
Essential fructosuria enzyme
Fructokinase
Fructose intolerance enzyme
Aldolase B
In a state of low blood sugar, which one is working: hexokinase of glucokinase
Hexokinase working because there is not a bunch of Glucose-6-phosphate inhibiting it
What is the on/off switch for glycolysis? When it is increased how does it affect glycolysis? Decreased?
Fructose 2,6 Bisphosphate
When it is increased glycolysis is on, when it is low no glycolysis and gluconeogenesis is turned on
Neurologic defects, lactic acidosis, increased serum alanine starting in infancy; but NO hypoglycemia
pyruvate dehydrogenase complex deficiency. Tx w/ increased intake of ketogenic nutrients
Rotenone inhibits whic ETC complex
Complex I
Antimycin A inhibits which ETC complex
Complex 3
Cyanide, Carbon monoxide, azide (the -ides) inhibit which ETC complex
IV
Oligomycin directly inhibits mitochondrial ATP synthase in which complex
Complex V
2,4-Dinitrophenol and aspirin have what effect on ETC?
Uncoupling agents, produce heat.
What enzyme steps in when there is a defect in fructokinase leading to essential fructosuria
Hexokinase
When fructose-1-phosphate accumulates in the hereditary deficiency of aldolase B (hereditary fructose intolerance), what is causing the inhibition of glycogenolysis and gluconeogensis?
Buildup of F1P decreases available phosphate
The absence of galactose-1-phosphate uridyltransferase in classic galactosemia patients causes failure to thrive, hepatomegaly, infantile cataracts and an increased risk for sepsis due to what organism?
E.coli
What tissues have only aldose reductase and not sorbitol dehydrogenase and are more likely to get osmotic damage? (LuRKS)
Lens has primarily aldose reductase.
Retina, Kidneys, Schwann cells have ONLY aldose reductase
Primary lactase deficiency is due to
Absence of lactase-persistent allele
Stool has decreased pH in lactase deficiency. But biopsy reveals normal mucosa
N-acetylglutamate is an allosteric activator of the urea cycle enzyme that is in the mitochondria. What is this enzyme
Carbamoyl phosphate synthetase 1 (ONE*)
Converts CO2 and NH3 into carbamoyl phosphate
X-linked recessive disorder where excess carbamoyl phosphate is converted to orotic acid (part of the pyrimidine pathway)
OTC deficiency. Will see increased orotic acid in blood and urine, decreased BUN, and SYMPTOMS OF HYPERAMMONEMIA
What amino acid does Heme start from
Glycine
Niacin, Serotonin, Melatonin all come from?
Tryptophan
Tyrosine, DOPA, Dopamine, NE, Epi all come from?
Phenylalanine
What are the BCAAs that must be avoided due to a decrease in branched-chain alpha-ketoacid dehydrogenase (B1) present in Maple Syrup Urine Disease
I Love Vermont maple syrup
Isoleucine, Leucine, Valine
Cystathione synthase deficiency is a cause of Homocystinuria, how do you treat it
Decrease methionine
Increase cysteine, B6, B12, and folate
What crystals will be seen in Cystinuria
Hexagonal cystine stones
Hereditary defect of renal PCT and intestinal amino acid transporter that prevents reabsorption of Cystine, Ornithine, Lysine, Arginine
Cystinura
Urinary cyanide-nitroprusside test is diagnostic for ?
Cystinuria
Treatment for cystinuria
Urinary alklinization using potassium citrate and acetazolamide
Chelating agents ie penicillamine, to increase the solubility of cystine stones
Propionic acidemia is caused by a deficiency of propionyl-CoA carboxylase, leading to increased propionyl-CoA, and decreased methylmalonic acid. What are the substances that metabolize into propionyl-CoA that should be avoided in these patients
Valine, Odd-chain fatty acids, Methionine, Isoleucine, Threonine
(VOMIT)
Deficiency in Glucose-6-phosphatase
Von Gierke
Lysosomal acid a-1,4-glucosidase (acid maltase) with a-1,6-glucosidase activity deficiency
Pompe disease (type II GSD)
Debranching enzyme (a-1,6-glucosidase) deficiency
Cori Disease (type III)
Flat venous lactate curve w/ normal rise in ammonia levels during exercise
McArdle
Lysosomes w/ onion skinning, no hepatosplenomegaly, hyperreflexia, hyperacusis caused by deficient hexosaminidase A
Tay-Sachs