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375 Cards in this Set
- Front
- Back
Histone octamers consist primarily of which two amino acids?
|
Lysine and Arginine (both positively charged)
|
|
What histones are nucleosome beads composed of?
|
H2A, H2B, H3, H4 (two sets each, form an octamer)
|
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What is the function of histone H1?
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H1 ties nucleosome beads together in a string.
|
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Which histone is not a part of the nucleosome core?
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H1
|
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What is the nucleosome core composed of?
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Two copies of H2A, H2B, H3, H4, and ~147 base pairs of DNA wrapped in L-handed 1.67 turns around it.
|
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What is heterochromatin?
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DNA that is condensed, transcriptionally inactive, and sterically inaccessible.
|
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What is euchromatin?
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DNA that is less condensed, is transcriptionally active, and is sterically accessible.
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What occurs to make heterochromatin into euchromatin?
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Acetylation of the histone structure causes the DNA to loosen around the nucleosome core.
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Which nucleotides compose DNA?
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Adenine, guanine, cytosine, thymine
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Which nucleotides compose RNA?
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Adenine, guanine, cytosine, uracil
|
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Which are the purines?
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Adenine and Guanine (both have two rings)
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Which are the pyrimidines?
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Cytosine, Uracil, and Thymine (all have one ring)
|
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How is uracil made?
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deamination of cytosine.
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Which pyrimidine is unique to DNA?
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thymine
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Which pyrimidine is unique to RNA?
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uracil
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What is the group attached to thymine?
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a methyl group
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Which nucleotide bonds are the strongest, resulting in higher melting temperatures when abundant?
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A-G (have three H-bonds)
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Which nucleotide bonds have only two H-bonds?
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A-T (creates lower melting temperatures)
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What special group is found on purines?
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N(10)-formyl-tetrafolate
(two groups per purine) |
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Which amino acids are necessary for purine synthesis?
|
Glycine, Aspartate, Glutamine
|
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What is a nucleoside composed of?
|
base + ribose
|
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What is a nucleotide composed of?
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base + ribose + phosphate linked with 5'-3' phosphodiesterase bond
|
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What is the purine precursor?
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IMP (inosine monophosphate)
|
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What is the pyrimidine precursor?
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orotate
(with PRPP, phosphoribosyl pyrophosphate, added later) |
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Ribonucleotides are converted to deoxyribonucleotides by?
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ribonucleotide reductase
|
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Which two pathways involve carbamoyl phosphate?
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(1) de novo pyrimidine synthesis (2) urea cycle
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Ornithine transcarbamoylase deficiency in the urea cycle causes what?
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An accumulation of carbamoyl phosphate, converted to orotic acid --> orotic acidemia.
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Orotic acidemia can be caused by defects in which two enzymes?
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Defects in orotic acid phosphoribosyltransferase or orotidine 5'-phosphate decarboxylase.
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What is the genetic inheritance of orotic acidemia?
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autosomal recessive
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Both of the enzyme defects possible in orotic acidemia ultimately cause?
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Lack of ability to convert orotic acid to UMP (uridine 5'-monophosphate)
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What are the findings in orotic aciduria?
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Increased urine orotic acid, folate independent megaloblastic anemia, failure to thrive, normal ammonemia.
|
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How do you treat orotic aciduria?
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Oral uridine. (works via the pyrimidine salvage pathway)
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What does adenosine deaminase deficiency cause?
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Decreased lymphocyte count (due to decreased DNA synthesis because excess ATP and dATP inhibit ribonucleotide reductase)
|
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Adenosine deaminase deficiency is one of the major causes of which disease?
|
SCID severe combined immunodeficiency disease
|
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What was the first disease to be treated by gene therapy?
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SCID
|
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What is the defect in Lesch-Nyhan syndrome?
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absence of HGPRT (hypoxanthine guanine phosphoribosyltransferase)
|
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What is the function of HGPRT?
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converts hypoxanthine to IMP
converts guanine to GMP |
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What happens in Lesch-Nyhan syndrome?
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Can't salvage purines: excess uric acid production.
|
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What is the clinical presentation of Lesch-Nyhan syndrome?
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Retardation, self-mutilation, aggression, hyperuricemia, gout, choreoathetosis, urate nephropathy.
|
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What is the mode of transmission of Lesch-Nyhan syndrome?
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x-linked recessive
|
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What is the precursor for purines?
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IMP (inosine monophosphate)
|
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What is the precursor for pyrimidines?
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Orotate (with PRPP added later)
|
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In DNA replication, what is a transition?
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Substituting a purine-purine, or pyrimidine-pyrimidine
transItion is Identical |
|
In DNA replication, what is a transversion?
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Substituting a purine for a pyrimidine, or vice versa.
transVersion = conVersion of type |
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What does unambiguous mean in relation to the genetic code?
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Each codon specifies for only 1 amino acid.
|
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In relation to genetic code, what does degenerate mean?
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Multiple codons may code for the same amino acid
|
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In relation to genetic code, what does commaless mean?
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Read from a fixed start point as continuous sequence of bases
|
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In genetic code, what does universal mean?
|
Genetic code is conserved throughout evolution.
|
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What are exceptions to universal code?
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Mitochondria, archaebacteria, Mycoplasma, and some yeasts
|
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What are exceptions to commaless code?
|
Some viruses
|
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What is a non-degenerate code?
|
Methionine is only coded for by AUG (start)
|
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What is a silent DNA mutation?
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Same amino acid, change at 3rd position due to tRNA wobble
|
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What is a missense mutation?
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The amino acid has been changed, but is similar in chemical structure
|
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What is a nonsense mutation?
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Change resulting in an early STOP codon
stop the nonsense! |
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What is a frame shift mutation?
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Change resulting in misreading of downstream codons. Results in truncated, non-functional protein.
|
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What is the origin of replication?
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Genomic sequence were replication begins. Is single in prokaryotes, and multiple in eukaryotes.
|
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What is the role of helicase?
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It unwinds DNA at the replication fork.
|
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What prevents DNA from reannealing during replication?
|
Single-stranded binding proteins
|
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What is the role of DNA topoisomerases?
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They create a nick in the helix to relieve supercoil during replication.
|
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What is the role of primase?
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It makes an RNA primer on which DNA polymerase III can initiate replication (in prokaryotes)
|
|
What is the role of DNA polymerase III?
|
(prokaryotes)
1. It elongate the leading strand by adding deoxynucleotides to the 3' end. 2. Elongates lagging strand too. 3. 3' --> 5' exonuclease proofreading activity |
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What is the moe of flouroquinolones?
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They inhibit DNA gyrase (specific prokaryotic topoisomerase)
|
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What is the role of DNA polymerase I?
|
(prokaryote) Degrades the RNA primer with 5' --> 3' exonuclease activity and fills gap with DNA.
|
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What is the role of DNA ligase?
|
Seals
|
|
What is nucleotide repair?
|
Endonucleases release oligonucleotides containing damaged bases, DNA polymerase fills and ligase reseals the gap.
|
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What is base excision repair?
|
Glycosylases recognize/remove damaged bases, AP endonucleases cut DNA at apyrimidic site, empty sugar removed, gap is filled/sealed.
|
|
What is mismatch repair?
|
Unmethylated new string has mismatched nucleotides removed, gap is filled/sealed.
|
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What is the defect in XP?
|
Xeroderma pigmentosum: mutated nucleotide excision repair --> prevents repair of thymidine dimers.
|
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What is the defect in HNPCC?
|
Mutated mismatch repair (APC gene)
|
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What are the three types of DNA repair?
|
Nucleotide excision repair, base excision repair, and mismatch repair
|
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On incoming DNA, whre is the triphosphate?
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On the 5' end
|
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How is mRNA read?
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5' --> 3'
|
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What is the direction of protein synthesis?
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N --> C
|
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Which is the most abundant RNA?
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rRNA
rampant |
|
What is the longest type of RNA?
|
mRNA
massive |
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What is the smallest type of RNA?
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tRNA
tiny |
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What is the prokaryotic start codon coding for?
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formyl-methionine (f-met)
|
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What are the mRNA stop codons?
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UGA you go away
URA you are away UAG you are gone |
|
List the organization of a gene:
|
5'- promoter - enhancer - promoter - tata - initiation site - coding region of exons/introns - aataa tail - 3'
|
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Where does RNA polymerase (or other transcription factors) bind DNA?
|
the promoter site
|
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What is the result of promoter site mutations?
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dramatic decrease in amount of that gene transcribed
|
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RNA polymerase I makes?
|
rRNA in eukaryotes
|
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RNA polymerase II makes?
|
mRNA in eukaryotes
It opens DNA at promoter site |
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RNA polymerase III makes?
|
tRNA in eukaryotes?
|
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What is the order of RNA as it is used?
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rRNA, mRNA, tRNA
|
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What does alpha-amanitin cause liver failure?
|
It inhibits RNA polymerase II (found in death cap mushrooms)
|
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How is prokaryotic RNA synthesized?
|
by RNA polymerase
|
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Where does RNA processing occur?
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in the nucleus
|
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What are the steps in RNA processing?
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(1) 5' cap of 7-methylguanosine
(2) 3' tail polyadenylation ~200 A (3) Splicing out of introns |
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What is hnRNA?
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unprocessed nuclear RNA
|
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What is mRNA
|
Processed (capped/tailed) RNA
|
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What is the polyadenylation signal, and how is it transcribed.
|
AAUAAA, transcribed by poly-a-polymerase w/o a template
|
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How does pre-mRNA splicing occur?
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(1) Transcript combines with snRNPs, et to form spliceosome
(2) Lariat intermediate generated (3) Lariate releases introns, joins together exons. |
|
What is the defect in lupus (regarding RNA)?
|
Antibodies to spliceosomal snRNPs
|
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Which portion of hnRNA contains the actual genetic information?
|
the exons
|
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An example of alternative splicing mutations in seen in?
|
the beat-thalassemia mutations
|
|
Describe tRNA structure:
|
Secondary structure is a cloverleaf. Anticodon end is opposite 3' aminoacyl end.
|
|
Where is the amino acid bound to tRNA?
|
the 3' end (covalently)
|
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What is at every 3' end of tRNA?
|
CCA
|
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What is responsible for the accuracy of amino acid selection in tRNA formation?
|
aminoacyl-tRNA synthetase and binding of charged tRNA
|
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What is the moe of tetracylines?
|
they bind the 30S subunit (prevent attachment of aminoacyl-tRNA)
|
|
What is the function of aminoacyl-tRNA synthetase?
|
scrutinizes aa before and after it binds it to tRNA, can hydrolyze incorrectly bound aa
|
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What occurs in protein synthesis initiation?
|
GTP hydrolysis activates initiation factors to assemble 40S with initiator tRNA
|
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What occurs in protein synthesis elongation?
|
(1) Aminoacyl-tRNA binds to A site
(2) rRNA catalyzes peptide bonds, transfers aa to A site (3) ribosome advances 3 nucleotides toward 3' end moving peptidyl RNA to P site |
|
What occurs in protein synthesis termination?
|
completed protein is released via simple hydrolysis.
|
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What are the eukaryotic ribosomal subunits?
|
40S + 60S = 80S
|
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What are the prokaryotic ribosomal subunits?
|
30S + 50S = 70S
|
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What are the roles of ATP and GTP in protein synthesis?
|
ATP- Activation of tRNA
GTP- Gripping/Going of tRNA (translocation) |
|
What are the sequential sites on the ribosome in protein synthesis?
|
A site- incoming Aminoacyl tRNA
P site- Peptide growing site E site- holds Empty/Exiting tRNA APE |
|
What is the moe of aminoglycosides?
|
inhibit the formation of the initiation complex and cause misreading of mRNA
|
|
What is the moe of chloramphenicol?
|
inhibits the 50S pepetidyltransferase
|
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What is the moe of macrolides?
|
bind 50S, blocking translocation
|
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What is the moe of clindamycin?
|
binds 50S, blocking translocation
|
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What is the energy requirement of translation?
|
4 high-energy phosphoanhydride bonds
|
|
What is post-translational trimming?
|
Removal of N- or C-terminal propeptides from zymogens to generate mature protiens
|
|
What are some post-translational covalent alterations?
|
phosphorylation, glycosylation, and hydroxylation
|
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What is post-translational involved in proteasomal degradation?
|
attachement of ubiquitin to defective proteins
|
|
What are the phase in the cell cycle?
|
Mitosis, G1, (G0), S, G2
|
|
Which is the shortest part of the cell cycle?
|
mitosis
|
|
What are the stages of mitosis?
|
prophase, metaphase, anaphase, telophase
|
|
What are the two common tumor suppressors?
|
Rb and p53 normally inhibit G1-S progression
|
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What are some permanent cell types (remain in G0)?
|
Neurons, skeletal mm, cardiac mm, and RBCs
|
|
What are some stable cell types (enter G1 when stimulated)?
|
Hepatocytes, lymphocytes
|
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What are some labile cell types (never go to G0)?
|
Bone marrow, gut epithelium, skin, and hair follicles.
|
|
What are the main functions of the RER?
|
Synthesis of secretory protiens, and N-linked oligosaccharide addition to proteins
|
|
What are Nissl bodies?
|
the RER in neurons- synthesize enzymes (ChAT) and peptide neuromodulators
|
|
What is the function of free ribosomes?
|
Synthesis of cytosolic and organellar proteins
|
|
What are some RER-rich cells?
|
Mucus-secreting goblet cells on small intestine and Ab-secreting plasma cells
|
|
What is the function of the SER?
|
Site of steroid synthesis and detoxification of drugs and poisons
|
|
What are some SER-rich cells?
|
Hepatocytes, and adrenal cortical steroid-hormone secreting cells
|
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How are proteins targeted to lysosomes?
|
Golgi addition of mannose-6-phosphate
|
|
The golgi distributes?
|
protiens and lipids from ER to plasma membrane, lysosomes and secretory vesicles
|
|
The golgi modifies N-oligosaccharides on?
|
asparagine
|
|
The golgi takes protein cores and?
|
assembles proteoglycans with them, and sulfates the attached sugars.
|
|
The golgi sulfates?
|
proteoglycan sugars and selected tyrosine residues on proteins.
|
|
What is the function of COPI?
|
retrograde transport
Golgie --> ER |
|
What is the function of COPII?
|
anterograde transport
RER --> cis-Golgi |
|
What is the function of clathrin?
|
receptor-mediated endocytosis.
(trans-Golgi --> lysosomes, and plasma memb --> endosomes) |
|
What is the defect in I-cell disease?
|
Failure of golgi-mediated addition of mannose-6-phosphate to lysosome proteins.
|
|
What is the pathophysiology of inclusion cell disease?
|
Lysomal enzymes are not targeted to lysosomes, and are secreted out of the cell instead.
|
|
What is the clinical presentation of I-cell disease?
|
Coarse facies, clouded corneas, restricted joint movement, high plasma lysosomal enzymes. Fatal in childhood.
|
|
What are the major functions of microtubules?
|
Flagella, cilia, mitotic spindles, and slow axoplasmic transport in neurons
|
|
What is the composition of a microtubule?
|
Dimers of alpha- and beta-tubulin with 2ATP bound to each, polymerized into helical array.
|
|
What are some drugs that act on microtubules?
|
Mebendazole, thiabendazole, griseofulvin, vincristine, vinblastine, paclitaxel, colchicine.
|
|
What is the function of dynein?
|
A molecular motor protein: retrograde transport to microtubule ( + to -)
|
|
What is the function of kinesin?
|
A molecular motor protein: anterograde transport to microtubule (- to +)
|
|
What is the defect in Chediak-Higashi syndrome?
|
Defective microtubule polymerizaion (decreased phagocytosis).
|
|
What is the clinical presentation in Chediak-Higashi syndrome?
|
Recurrent pyogenic infections, partial albinism, and peripheral neuropathy.
|
|
What is the composition of cilia?
|
9 +2 arrangement of microtubules
|
|
What is the function of axonemal dynein?
|
It is an ATPase linking the peripheral 9 doublets, differential sliding of the doublets causes cilia bending.
|
|
What is the defect in Kartagener's syndrome?
|
Immotile cilia due to a dynein arm defect
|
|
What is the clinical presentation of Kartagener's syndrome?
|
Male/female infertility, bronchiectasis, recurrent sinusitis.
|
|
What condition is associated with Kartagener's syndrome?
|
situs inversus
|
|
What are the functions of actin and myosin?
|
Form microvilli, muscle contraction, cytokinesis (post-mitosis pinch-off), adherens junctions.
|
|
What are the functions of intermediate filaments?
|
Form desmin, cytokeratin, glial fibrillary acid proteins, neurofilaments, and vimentin.
|
|
What is vimentin?
|
The dynamic structure of fibroblasts. Useful immunohisto marker for sarcoma.
|
|
What is defect/presentation of Alexander disease?
|
Altered glial fibrillary acid proteins, hence defective myelin sheaths. Phys/mental retard, dementia, large head/brain, spasticity, and seizures.
|
|
What are the main components of the lipid bilayer?
|
Cholesterol (~50%), phospholipids (~50%), sphingolipids, glycolipids, and proteins.
|
|
What is the effect of high cholesterol or long saturated fatty acid content in the lipid bilayer?
|
Increased melting temperature, decreased fluidity.
|
|
What does vimentin staining indicate?
|
connective tissue cells
|
|
What does desmin staining indicate?
|
muscle cells
|
|
What does cytokeratin staining indicate?
|
epithelial cells
|
|
What does GFAP staining indicate?
|
neuroglial cells
|
|
What does neurofilament staining indicate?
|
neurons
|
|
What is exchanged by the Na/K-ATPase?
|
3 Na+ go out
(ATP --> ADP) 2 K+ come in |
|
What is the moe of ouabain?
|
it binds extracellularly to the K+ site of the Na/K-ATPase (inhibits pump)
|
|
What is the moe of cardiac glycosides?
|
Directly inhibit the Na/K-ATPase, indirectly inhibitting Na/Ca exchanger. Increased [Ca++] = increased contractility
|
|
Where is type I collagen found?
|
bone, skin, tendon, dentin, fascia, cornea, late wound repair
|
|
Where is type II collagen found?
|
Cartilage, vitreous body, nucleus pulposus
|
|
Where is type III collagen found?
|
Reticulin: skin, blood vessels, uterus, fetus, granulation tissue
|
|
Where is type IV collagen found?
|
Basement membranes or basal lamina
|
|
What are the six steps in collagen synthesis?
|
RER synthesis, ER hydroxylation, ER glycosylation, exocytosis, proteolytic processing, and cross-linking.
|
|
Describe RER synthesis of collagen?
|
Preprocollagen (alpha chains) translated, usually Gly-X-Y where X = proline, hydroxyproline, or hydroxylysine.
|
|
Describe ER hydroxylation of collagen?
|
Specific proline and lysine residues are hydroxylated
|
|
Describe ER glycosylation of collagen?
|
Pro-alpha-chain lysine residues are glycosylated, triple helical procollagen is formed
|
|
Outside the fibroblast, what happens to collagen?
|
Terminal region cleavage makes insoluble tropocollagen, covalent lysine-hydroxylysine cross-link makes collagen fibrils
|
|
What are the cofactors needed in collagen synthesis and formation?
|
Vitamin C (Pro and Lys hydroxylation in ER) and Cu++ (lysly oxidase crosslinkages to form fibrils)
|
|
What is the defect in Menkes disease?
|
Mutations in ATP7A, inability to transport copper into blood stream
|
|
What is the clinical presentation of Menkes disease?
|
Hypopigmentation, kinky hair, cerebral degeneration or hemorrhage, hypothermia, low serum Cu++ and ceruloplasmin.
|
|
What is the defect in Ehlers-Danlos syndrome?
|
Extracellular cleavage of terminal regions on procollagen is defective, can't form tropocollagen
|
|
Which collagen is most effected in Ehlers-Danlos syndrome?
|
collagen type III
|
|
What is the clinical presentation of Ehlers-Danlos syndrome?
|
Hyperextensible skin, bleeding/bruising, hypermobile joints.
|
|
What conditions are associated with Ehlers-Danlos syndrome?
|
Joint dislocation, berry aneurysms, organ rupture
|
|
What is the defect in osteogenesis imperfecta?
|
abnormal type I collagen (rich in glycine and proline)
|
|
What is the clinical presentation of IO tarda?
|
Multiple fractures w/min trauma, blue sclerae, hearing loss, dental imperfections
|
|
What is the mode of inheritance for IO tarda?
|
autosomal dominant
|
|
What is the clinical presentation in OI congenita?
|
fatality in utero or neonatal period
|
|
What is the incidence of osteogenesis imperfecta?
|
1:10,000
|
|
What is the defect in Alport's syndrome?
|
Variety of gene defects --> abnormal collagen type IV
|
|
What is the clinical presentation of Alport's syndrome?
|
nephritis, deafness and maybe ocular disturbances
|
|
What is the defect in Marfan's syndrome?
|
Defect in fibrillin, can't provide scaffolding for tropoelastin
|
|
What is the pathogenesis in alpha1-antitrypsin deficiency?
|
Elastase is not broken down, thus degrades elastin in the lungs, large arteries, ligaments, vocal cords, ligamentum flava
|
|
What product do you want in PCR?
|
An amplified specific DNA sequence
|
|
What is the blotting procedures acronym?
|
SNoW DRoP
Southern DNA Northern RNA Western Protein |
|
Which blotting procedure do you use to evaluate DNA?
|
Southern
|
|
Which blotting procedure do you use to evaluate RNA?
|
Northern
|
|
What blotting procedure do you use to evaluate proteins?
|
Western blot
|
|
What can microarrays be used for?
|
To profile gene expression levels, or to detect SNPs (single nucleotide polymorphisms)
|
|
Which test is sensitive, and then which is specific when looking for Lyme disease?
|
ELISA (1st- very sensitive)
Western blot (2nd- v. specific) |
|
What is FISH used for?
|
Localization of genes, and direct visualization of anomalies
|
|
What binds to what in FISH?
|
flour-in-situ-hybrid: DNA or RNA probe binds specific gene of interest
|
|
How does Sanger DNA sequencing work?
|
dideoxynucleotides halt DNA at each base, generates various length sequences. Electrophorese to deduce original sequence.
|
|
How is DNA cloned?
|
Insertion into abx resistant bacterial plasmids at 4-6 bp palindromic sequences, reverse transcriptase creates cDNA library (lacks introns)
|
|
What is pleiotropy?
|
When 1 gene has more than 1 effect on an individuals phenotype
|
|
What is imprinting?
|
the deactivation of either the maternal or paternal copy of a gene so only one is expressed
|
|
What is linkage disequilibrium?
|
When two alleles at linked loci to occur more frequently together than expected: measured in a population
|
|
What is lyonization?
|
random X inactivation in females
|
|
What is locus heterogeneity?
|
Mutations at different loci producing the same phenotype (marfanoid in Marfans, MEN 2B, and homocystinuria)
|
|
What is heteroplasmy?
|
Presence of normal and mutated mtDNA --> variable expression in inherited mitochondrial disease.
|
|
What is uniparental disomy?
|
Offspring recieves two copies of a chromosome from one parent, none from the other parent.
|
|
If in Hardy-Weinberg equilibrium, disease prevalence is?
|
p^2 + 2pq + q^2 = 1
|
|
If in Hardy-Weinberg equilibrium, allele prevalence is?
|
p + q = 1
|
|
If in Hardy-Weinberg equilibrium, what is the heterozygote prevalence?
|
2pq
|
|
If in Hardy-Weinberg equilibrium, the prevalence of x-linked disease is?
|
q in males and q^2 in females
|
|
Hardy-Weinberg equilibrium assumes?
|
1. No mutation at locus
2. No selection for mutant locus 3. Random mating 4. No migration |
|
The defect in Prader-Willi is?
|
Imprinted maternal genes, and deletion of the active paternal genes on Chr 15 (or uniparental disomy)
|
|
The defect in Angelman's syndrome is?
|
Imprinted paternal genes, and deletion of the active maternal genes on Chr 15 (or uniparental disomy)
|
|
What is the clinical presentation of Prader-Willi syndrome?
|
Mental retardation, hyperphagia, obesity, hypogonadism, hypotonia
|
|
What is the clinical presentation of Angelman's syndrome?
|
"happy puppet". Mental retardation, seizures, ataxia, inappropriate laughter.
|
|
Who is affected by a x-linked recessive disease?
|
Sons of heterozygous mothers have 50% change
|
|
Who is affected by a x-linked dominant disease?
|
all female offspring of affected fathers are diseased
|
|
Who is affected in mitochondrial disease inheritance?
|
All offspring of affected mother may show signs of disease
|
|
What is the pathogenesis of Leber's hereditary optic neuropathy?
|
Degen of retinal ganglion cells and axons. Loss of vision, WPW syndrome, mt inheritance.
|
|
Achondroplasia: defect and presentation?
|
AD. Signal defect of FGFr3. Dwarfism (short limbs), asc'd w/paternal age
|
|
ADPKD: defect and presentation?
|
90% defective APKD1 Chr 16
Bilateral enlargement, flank AD. pain, htn, renal fail. Asc'd w/polycystic liver dz, BERRY ANEURYSMS, mitral valve prolapse. Infantile is recessive. |
|
FAP: defect and presentation?
|
AD. Error in DNA repair. Adenomatous polyps after puberty --> cancer unless resected. Chr 5 deletion of APC gene.
|
|
Familial hypercholesterolemia: defect and presentation?
|
AD. Defect or absent LDL receptor. heterozy cholesterol ~300, homo ~700. MI maybe before 20, achilles or eyelid xanthomas, early atherosclerosis.
|
|
Hereditary hemorrhagic telangectasia: defect and presentation?
|
AD. Disorder of blood vessels. Telangectasia, recurrent epistaxis, skin discoloration, av malformations.
|
|
Hereditary spherocytosis: defect and presentation?
|
AD. Spheroid RBCs due to spectrin or ankrin defect. Hemolytic anemia, increased MCHC. Splenectomy curative.
|
|
Huntington's disease: defect and presentation?
|
AD. Chr 4 (CAG)x repeat disorder. Decreased GABA and ACh in brain, depression, prog demetia, chorieform mvmt, caudate atrophy.
|
|
Marfan's syndrome: defect and presentation?
|
AD. Fibrillin gene mutation. Tall, long extramities, arachnodactyly, cystic medial Ao necrosis, floppy mitral v, sublux of lenses.
|
|
Neurofibromatosis type 2: defect and presentation?
|
AD. NF2 gene on Chr 22. Bilateral acoustic neuroma, juvenile cateracts.
|
|
Tuberous sclerosis: defect and presentation?
|
AD. Adenoma sebaceum, 'ash leaf spots', corticol/retinal hamartomas, pheochromocytomas, cardiac rhabdomyomas, increase incidence of astrocytomas.
|
|
von Hippel-Lindau disease: defect and presentation?
|
AD. Deletion of VHL gene on Chr 3 causes constitutive expression of HIF trxn factor and activation of angiogenic GFs. Hemagioblastomas of retina/cerebellum/medulla, half dev. multiple bilateral renal cell carcinomas, et.
|
|
What is the defect in CF?
|
AR. Deletion of Phe at position 508 in CFTR gene on Chr 7. Defective Cl- channel--> secrete abnormally thick mucus
|
|
What is the clinical presentation of CF?
|
Recurrent pulm infx (s. aureus, pseudomonas), chronic bronchitis, bronchietasis, pancreatic insufficiency, meconium ileus
|
|
What is the effect of the deletion in cystic fibrosis?
|
Improper protein folding, channel degraded before reaching plasma membrane
|
|
What is the cause of infertility in cystic fibrosis affected males?
|
Absence of the vas deferens.
|
|
What deficiency might accompany CF?
|
ADEK fat-soluble vitamins
|
|
What is the most common lethal genetic disease in Caucasians?
|
cystic fibrosis
|
|
Who do you diagnose CF?
|
PCR of the Chr 7 mutation and/or? increased concentration of Cl- ions in the sweat
|
|
What is the treatment for CF?
|
N-acetylcysteine (cleaves disulfide bond in mucous glycoproteins)
|
|
Which are the X-linked recessive disorders?
|
Be Wise, Fools GOLD Heeds Silly Hope. Brutons agammaglobulinemia, Wiskott-Aldrich syndrome, Fabrys, G6PD deficiency, Ocular albinism, Lesch-Nyhan synd, Duchenne's/Beckers, Hunter's synd, Hemophilia A/B
|
|
What is the defect in Duchenne's muscular dystrophy?
|
X-linked frame shift mutation causing deletion of dystrophin gene
|
|
What is the clinical presentation of Duchenne's?
|
Pelvic girdle wkns, calf pseudohypertrophy, cardiac myopathy, under 5 yrs old, Gower's manuever
|
|
What is dystrophin important?
|
it anchors mm fibers in skeletal and cardiac muscle
|
|
What is the DMD gene suspectible to mutation?
|
the dystrophin gene is the longest known human gene
|
|
How do you diagnose muscular dystrophies?
|
increased CPK and mm biopsy
|
|
What is the defect in Becker's muscular dystrophy?
|
x-linked mutated dystrophin gene, is less severe than not having gene at all
|
|
What is the defect in fragile X?
|
X-linked defect affecting methylation of FMR1 gene (asc'd w/chr breakage) (CGG)x repeats
|
|
What is the clinical presentation of Fragile X syndrome?
|
Long face, long jaw, macroorchidism, large everted ears, autism, mitral prolapse.
|
|
What are the trinucleotide expansion diseases?
|
Huntington's disease, Myotonic dystrophy, Friedrich's ataxia, fragile X syndrome (Hunting for My Friend Xavier)
|
|
Which condition has (CAG)x repeats?
|
Huntington's disease
|
|
Which condition has (CTG)x repeats?
|
Myotonic dystrophy
|
|
Which condition has (CGG)x repeats?
|
fraGile x
|
|
Which condition has (GAA)x repeats?
|
Friedrich's ataxia
|
|
What is the incidence of trisomy 21?
|
1:700
|
|
What is the incidence of trisomy 18?
|
1:8,000
|
|
What is the incidence of trisomy 13?
|
1:15,000
|
|
What are some clinical findings in trisomy 21?
|
Ment retard, epicanthal folds, simian crease, flat facies, 1st-2nd toe gap, duodenal atresia, congenital heart disease (s primum ASD)
|
|
What conditions are associated with Down's syndrome?
|
Alzheimers and increased risk of ALL (acute lymphoblastic leukemia)
|
|
What is the main cause of the most common chromosomal disorder?
|
95% non-disjunction of homologous chr (trisomy 21)
|
|
What is the effect of advanced maternal age on trisomy 21?
|
Over 45 yrs 1:25 incidence (only 1:1,500 when mother is 20 yo)
|
|
What are non-nondisjunction causes of trisomy 21?
|
4% Robertsonian translocation
1% Down mosaicism |
|
What is the most common cause of congenital mental retardation?
|
Down's - trisomy 21
|
|
How is Trisomy 21 reflected in the quad screen?
|
Decreased alpha-FP, and estriol.
Increased b-HCG, and inhibin A. |
|
What is the clinical presentation of trisomy 18?
|
severe mental retard, rocker-bottom feet, micrognathia, low set ears, clenched hands, prominent occiput, congenital heart disease, death by 1 yo
|
|
What is the clinical presentation of trisomy 13?
|
severe mental retard, rocker-bottom feet, micropthalmia, cleft lip/palate, holoproencephay, polydactyly, congenital heart disease, death by 1 yo
|
|
What are the names of trisomy 21, 18, and 13 respectively?
|
Downs, Edwards, Patau's
|
|
If nondisjunction of chr 21 occurs at anaphase I, what are the chances of offspring being affected?
|
100%
|
|
If nondisjuntion of chr 21 occurs at anaphase II, what are the chances of offspring being affected?
|
25%--- well?? maybe 1/3 so 33%?
|
|
What is Robertsonian translocation?
|
Long arms of 2 acrocentric chromosomes fuse, and short arms are lost
|
|
Which chr are involved in Robertsonian translocations most often?
|
13, 14, 15
21, 22 |
|
What is a possible result in chromosomal inversions?
|
decreased fertility
|
|
Which type of chromosome inversion is worse?
|
Probably pericentric (involves centromere) because it proceeds through meiosis.
|
|
What is the defect in Cri-du-chat syndrome?
|
Congenital microdeletion of short arm of chr 5
|
|
What are the findings in Cri-du-chat syndrome?
|
Microcephaly, mod-severe mental retard, high pitched crying, epicanthal folds, cardiac abnormalities
|
|
What is the defect in William's syndrome?
|
Microdeletion in long arm of chr 7 (includes elastin gene)
|
|
What are the findings in William's syndrome?
|
Ment retard, 'elfin' facies, increased sens to Vit D (hypercalcemia), well-dev'd verbally, extremely friendly w/strangers, CV abnormalities
|
|
What is the defect in 22q11 deletion syndromes?
|
Aberrant development of the 3rd and 4th branchial pouches
|
|
DiGeorge syndrome: defect and presentation?
|
22q11 deletion. thymic aplasia, cardiac defects, hypocalcemia
|
|
Velocardiofacial syndrome: defect and presentation?
|
22q11 deletion. cleft palate, abnormal facies, cardiac defects
|
|
Fat soluble vitamins, and place of absorption?
|
ADEK- absorbed in ileum w/help of pancreas
|
|
Other names for B1?
|
Thiamine
TPP (thiamine pyrophosphate-active) |
|
Other names for B2?
|
Riboflavin
FAD FMN |
|
Other names for B3?
|
Niacin
NAD+ Nicotinamide |
|
Other names for B5?
|
Pantothenic acid
CoA |
|
Other names for B6?
|
Pyridoxine
PLP (pyridoxal phosphate) |
|
Other name for B12, and unique mineral it contains?
|
Cobalamin
-contains selenium |
|
Other name for Vit C?
|
Ascorbic acid
|
|
Other name for B7?
|
Biotin
|
|
Other name for B9?
|
Folate
|
|
Which water soluble vitamins have bodily stores?
|
B12 (6-7 years)
Folate (3-4 months) |
|
B-complex deficiencies often result in what three presenting symptoms?
|
Dermatitis, glossitis, and diarrhea
|
|
Vitamin A is essential for differentiation of epithelial cells in to which specialized cells?
|
-pancreatic cells
-mucus-secreting cells |
|
What are the sequelae of vit A deficiency?
|
Night blindness, dry skin, squamous metaplasia w/ corneal opacification
|
|
What occurs in Vit A toxicity?
|
Arthralgias, fatique, HA, skin changes, sore throat, alopecia, teratogenic (cleft palate, cardiac abnormalities)
|
|
What four major enzymes require B1 as a cofactor?
|
Pyruvate dehydrogenase, a-ketoglutarate, transketolase, branched chain aa dehydrogenase
|
|
What results from B1 deficiency?
|
Wernicke-Korsakoff, Dry/Wet Beriberi
|
|
How does Wernicke-Korsakoff present?
|
confusion, ophthalmoplegia, ataxia, memory loss, confabulation, personality change
|
|
What is the function of B2?
|
Cofactor in oxidation/reduction (FAD/FMN) --> riboFLAVIN
|
|
How does a deficiency in B2 present?
|
Cheilosis, corneal vascularization
|
|
What is the function of Vit B3?
|
Redox rxn (NAD+, NADP+ constituent)
|
|
What is Vit B3 derived from?
|
tryptophan
|
|
How many ATP are in niacin?
|
3
|
|
How many ATP are in riboflavin?
|
2
|
|
How does a deficiency of B3 present?
|
Glossitis, if severe then; pellagra
|
|
What can cause severe B3 deficiency?
|
Hartnup disease, malignant carcinoid syndrome, INH treatment.
|
|
What are the 3 D's of B3 deficiency?
|
Diarrhea, Dermatitis, Dementia
|
|
How does B3 excess present?
|
Facial flushing
|
|
What is the function of B5?
|
essential component of CoA and fatty acid synthatse
|
|
How does a B5 deficiency present?
|
Dermatitis, enteritis, alopecia, adrenal insufficiency
|
|
What are the functions of B6?
|
Cofactor in transamination, decarboxylations, glycogen phosphorylase, cystathionine synthase, heme synthesis, synthesis of niacin.
|
|
How does B6 deficiency present?
|
Convusions, hyperirritability, peripheral neuropathy, sideroblastic anemias
|
|
What can induce B6 deficiency?
|
INH or oral contraceptive usage
|
|
What is the molecular function of B12?
|
Cofactor for homocysteine methyltransferae and methylmalonyl-CoA mutase.
|
|
What is the presentation of a cobalamin deficiency?
|
Macrocytic megaloblastic anemia, hypersegmented PMNs, neuro (paresthesias, subacute combined degen)
|
|
What is the dietary source for B12?
|
animal products
|
|
Is there a reserve pool for B12 in the body?
|
Several years worth in the liver
|
|
What are the main causes of cobalamin deficiency?
|
1. Malabsorption (sprue, diphyllobothrium)
2. Lack of IF 2. Absence of terminal ileum |
|
What is the Schilling test?
|
Give labeled B12. If less than 10% in urine, give with intrinsic factor.
|
|
What is the molecular function of folic acid?
|
Conversion to tetrahydrofolate for 1-C/methylation transfer reactions (especially nitrogenous bases in DNA/RNA)
|
|
What is the presentation of folic acid deficiency?
|
Macrocytic megaloblastic anemia (neuro is fine)
|
|
When are folate deficiencies seen?
|
Pregnancy, alcoholism, phenytoin, sulfonamides, MTX
|
|
What is the role of S-adenosyl-methionine?
|
ATP + methionine = SAM
Converts NE to Epi. |
|
What cofactors are required to convert NE to Epi?
|
S-adenosyl-methionine requires B12 and folate to convert NE to Epi.
|
|
What is the molecular function of biotin?
|
Cofactor for carboxylation enzymes
|
|
What reactions require biotin?
|
1. pyruvate carboxylate --> oxaloacetate
1. acetyl-CoA carboxylase --> malonyl-CoA 3. propionyl-CoA carboxylase --> methylmalonyl-CoA |
|
What is the presentation of a biotin deficiency?
|
Dermatitis, alopecia, enteritis
|
|
What can cause a biotin deficiency?
|
antibiotic use or excessive raw eggs (avidin avidly binds biotion)
|
|
What are the roles of ascorbic acid?
|
1. Antioxidant
2. Keeps Fe2+ reduced for absorption 3. Needed for Proline and lysine hydroxylation in collagen synthesis 4. Necessary for dopamine beta-hydroxylase conversion of dopamine to NE |
|
What is the presentation of Vitamin C deficiency?
|
Scurvy: swollen gums, bruising, anemia, poor wound healing
|
|
What is the storage form of Vitamin D?
|
25-hydroxycholecalciferol
|
|
What is the active form of Vitamin D?
|
1,25-(OH)2 D3
Calcitriol |
|
What is the presentation of vitamin D deficiency?
|
Hypocalcemic tetany
Adults- osteomalacia Kids- rickets |
|
What clinical signs can be elicited in vitamin D deficiency?
|
Troussou- carpal spasm w/BP cuff
Chovstak- tap face elicits facial spasm |
|
What form of vitamin D is ingested from plants?
|
D2
Ergocalciferol |
|
What form of vitamin D is ingested from milk, or son exposed skin?
|
D3
Cholecalciferol |
|
What is the function of vitamin E?
|
Antioxidant
(especially erythrocytes and cell membranes) |
|
What is the presentation of vitamin e deficiency?
|
Hemolytic anemia (increased erythrocyte fragility), mm weakness, neurodysfunction
|
|
What is the function of vitamin K?
|
Catalyzes gamma-caboxylation of glutamic acid residues on clotting proteins
|
|
What is the presentation of vitamin K deficiency?
|
Neonatal hemorrhage with increase PT, and aPTT, but normal bleeding time.
-Also with prolonged abx use |
|
Vitamin K is necessary for the synthesis of which clotting factors?
|
II, VII, IX, X, protein C and S
|
|
What is a vitamin K antagonist?
|
Warfarin
|
|
What is the molecular function of zinc?
|
Formation of zinc fingers (transcription factor motiff), and the activity of 100s of enzymes
|
|
What is the presentation of a zinc deficiency?
|
Delayed wound healing, hypogonadism, decreased adult hair, dysgeusia, anosmia, predisposition of etOH cirrhosis
|
|
What is the sequence of ethanol metabolism?
|
Ethanol (alcohol dehydrogenase) --> Acetylaldehyde (acetylaldhyde dehydrogenase) --> Acetate
|
|
What is the limiting reagent in ethanol metabolism?
|
NAD+
|
|
What does fomepizole inhibit?
|
alcohol dehydrogenase in the cytoplasm
|
|
What does disulfiram inhibit?
|
acetaldehyde dehydrogenase in mitochondria
(accumulation contributes to hangover) |
|
How does alcohol dehydrogenase operate?
|
zero order kinetics
|
|
What causes ethanol hypoglycemia?
|
Ethanol metabolism increases NADH/NAD+ liver ratio, shuntin pyruvate to lactate and oxaloaceteate to malate, inhibiting gluconeogenesis and stimulated FA synthesis
|
|
Kwashiorkor
|
Protein malnutrition
Protein deficient MEAL: malnutrition, edema, anemia, fatty liver |
|
Marasmus
|
energy malnutrition--> muscle wasting
|
|
What metabolism occurs in the mitochondria?
|
FA oxidation, acetyl-CoA production, TCA cycle, oxidative phosphorylation
|
|
What metabolism occurs in the cytoplasm?
|
Glycolysis, FA synthesis, HMP shunt, protein synthesis (RER), steroid synthesis (SER)
|
|
What reactions metabolize in the cytoplasm and mitochondria?
|
Heme synthesis, Urea cycle, Gluconeogenesis
HUGs take two (locations). |
|
What does a glucokinase do?
|
Catalyzes the phosphorylation of glucose using one ATP
|
|
What does a kinase do?
|
Uses ATP to phosphorylate substrates
|
|
What does a phosphorylase do?
|
Adds inorganic phosphate to substrate w/o using energy
|
|
What does a phosphatase do?
|
Removes phosphate group from substrate
|
|
What does a carboxylase do?
|
Adds 1 carbon with the help of biotin
|
|
What is the rate determining enzyme of glycolysis?
|
phosphofructokinase-1 (PFK-1)
|
|
What is the rate determining enzyme of gluconeogenesis?
|
fructose-1,6-bisphosphatase
|
|
What is the rate determining enzyme of the TCA cycle?
|
isocitrate dehydrogenase
|
|
What is the rate determining enzyme of glycogen synthesis?
|
glycogen synthase
|
|
What is the rate determining enzyme of glycogenolysis?
|
glycogen phosphorylase
|
|
What is the rate determining enzyme of the HMP shunt?
|
glucose-6-phosphate dehydrogenase (G6PD)
|
|
What is the rate determining enzyme of de novo pyrimidine synthesis?
|
carbamoyl phosphate synthetase II
|
|
What is the rate determining enzyme of de novo purine synthesis?
|
glutamine-PRPP amidotransferase
|
|
What is the rate determining enzyme of the urea cycle?
|
carbamoyl phosphate synthetase I
|
|
What is the rate determining enzyme of fatty acid synthesis?
|
acetyl-CoA carboxylase (ACC)
-requires biotin |
|
What is the rate determining enzyme of fatty acid oxidation?
|
carnitine acyltransferase I
|
|
What is the rate determining enzyme of ketogenesis?
|
HMG-CoA synthase
|
|
What is the rate determining enzyme of cholesterol synthesis?
|
HMG-CoA reductase
|