Biochemistry Section-USMLE Step 1
which histone ties DNA-histone nucleosome beads into more condensed structures? -
H1
is DNA acidic or basic? - acidic
what type of aa are histones made of? are they acidic or basic? - lysine and arginine;
basic
is heterochromatic more accessible or less accessible to TF? euchromatin? - less; more
if a cell has a hyperchromatic or condensed nucleus is it undergoing transcription etc? -
no
what are chromosomes? during what part of the cell cycle are they found? in what
pathologic state would you see a lot of chromosomes? - highly condensed forms of
DNA; mitosis; neoplasia- highly dividing and thus hyperchromatic
what experiment is chromosomes used for? - karyotyping
are histones in heterochromatin or euchromatin more methylated? which had more
acetylated histones? - heterochromatin; euchromatin
what does guanine have on it? - a ketone
what does thymine have on it? - a methyl
deamination of what pyrimidine makes what? - cytosine to uracil
in what genetic code is uracil found in? in replace of what? - uracil; thymine
how many bonds does a G-C connection have? what type of bonds? how about a A-T?
- 3 hydrogen bonds; 2 hydrogen bonds
what amino acids are required in purine synthesis? which of these does pyrimidine
synthesis require also? - glutamine, aspartate, glycine; aspartate
what is the difference between a nucleotide and a nucleoside? - nucleoside is just the
ribose plus the base; nucleotide is the ribose plus the base but the phosphate bond
Is PRPP added later or first in pyrimidine synthesis? - later
,what is PRPP? how is it made? - its the ribose; its made from PRPP synthetase using
ribose 5 P from the HMP shunt
what is the precursor for both purines? - IMP
what is the precursor for pyrimidines? - orotate
which intermediate is involved in both pyrimidine synthesis and the urea cycle? -
carbamoyl phosphate
why does a deficiency in ornithine transcarbamoylase (urea cycle enzyme) result in an
increased production of orotic acid, the pyrimidine precursor? - because carbamaoyl
phosphate is involved in both urea cycle and pyrimidine synthesis
is CPSII or CPSI involved in pyrimidine synthesis? - CPSII
what three enzymes lead to orotic acid accumulation? what reactions are they involved
in? - ortinithine transcarbamoylase, orotic acid phosphoribosyltransferase, and orotidine
5 phosphate decarboxylase; urea cycle; last two are involved in conversion of orotic
acid to UMP (adding PRPP to orotic acid)
what step in pyrimidine synthesis requires aspartate? - carbamoyl phosphate to orotic
acid
what are the clinical symptoms of orotic aciduria? - increased orotic acid in urine,
megaloblastic anemia, +/- hyperammonemia
how do you differentiate the causes of orotic aciduria? - whether or not the patient is
also hyperammonemia (if yes, then OTC def)
how do you differentiate causes of megaloblastic anemia? - orotic aciduria
megaloblastic anemia can not be corrected with folic acid or vit B12
how do you treat orotic aciduria? how does this work? - oral uridine administration;
provides nucleosides and provides feedback inhibition
what converts dUMP to dTMP? what drug blocks this? - thymidylate synthase; 5-
Flourouracil
what drug blocks ribonucleotide reductase? what does this enzyme do? - hydroxurea;
deoxygenates ribose
what does ornithine transcarbamyolase do to carbamoyl phosphate? - converts it to
citrulline
what does 6 mercaptopurine do? - 6MP blocks de novo purine synthesis
,other than thymidylate synthase, what else is required to convert dUMP to dTMP? -
N5N10 methylene THF
After N5N10 methylene THF donates a methyl for conversion of dUMP to dTMP what is
it converted to? - DHF
what enzyme converts DHF to THF? what vitamin cofactor is used to transfer a methyl
from an amino acid to DHF? what amino acid is that? - dihydrofolate reductase; vitamin
B12; homocysteine
what happens to homocysteine after converting a methyl? - becomes methionine
how is THF converted to N5N10 Methylene? - using serine (which turns into glycine
after reaction)
what does methotrexate do? what step is this enzyme involved in? - it inhibits
conversion of DHF to THF by blocking dihyrdofolate reductase
what is the difference between methotrexate and trimethroprim? - trimethroprim inhibits
bacterial dihyrofolate reductase
what is adenosine/AMP converted to? through what enzyme? - inosine/IMP; adenosine
deaminase
GMP is degraded to guanosine which is degraded to guanine. What two options are
next? by what enzymes? - either salvage by HGPRT and PRPP or converstion to
xanthine and then to uric acid by xanthine oxidase
IMP is degraded to inosine and then to hypoxanthine. what two options are next? by
what enzymes? - either salvage by HGPRT and PRPP or conversion to xanthine and
then uric acid by xanthine oxidase
in what syndrome is HGPRT deficient? what is the inheritance pattern? - Lesch Nyhan
syndrome; X linked recessive
what is main lab finding in Lesch Nyhan syndrome? due to what enzyme deficiency?
what reaction is deficient? - uric acidemia; HGPRT; purine salvage
what are the main clinical symptoms of Lesch Nyhan syndrome? - self mutilation,
aggression, mental retardation, gout, hyperuricemia, choreathetosis
what is the major cause of SCID? what does SCID stand for? - adenosine deaminase
deficiency; Severe combined immunodeficiency disease
, what is the link between adenosine deaminase deficiency and decreased lymphocyte
count? - excess ATP and dATP has negative feedback inhibition on ribonucleotide
reductase which results in decreased DNA synthesis and thus decreased lymphocyte
count
what has negative feedback inhibition on ribonucleoside reductase? - ATP and dATP
what is methotrexate? - a folic acid analogue
what is given to prevent side effects when methotrexate is given? why does this work? -
folinic acid; does not require DHF
in the genetic code, what does unambiguous mean? - each codon specifies only one
amino acid
what does degenerate/redundant mean in terms of the genetic code? - codons may
encode same amino acid since there are only ~20 aa
what structures allows for degeneracy? - tRNA wobble
what is the exception to degeneracy in the genetic code? - methionine is only encoded
by AUG
what is the exception to the nonoverlapping/commaless aspect of the genetic code? -
some viruses
what is the exception to the universal aspect of the genetic code? - mitochondria,
archaebacteria, mycoplasma, and some yeasts
what are the three types of point mutations? - silent, misssense, nonsense
what is a clinical example of a missense mutation? - sickle cell disease- conversion of
hydroophillic glutamic acid to hyrdophobic valine
what is an example of a nonsense mutation? - beta thalassemia
what creates a frameshift mutation? what are some clinical examples? - insertion or
deletion of a number of nucleotides indivisible by 3; tay sachs, duchennes MD
what does topoisomerase do? I or II eukaryotic? - creates nicks in DNA to prevent
supercoiling; both!
what is DNA gyrase? - a topoisomerase II
what Ab class blocks DNA gyrase? - Flouroquinolones
which histone ties DNA-histone nucleosome beads into more condensed structures? -
H1
is DNA acidic or basic? - acidic
what type of aa are histones made of? are they acidic or basic? - lysine and arginine;
basic
is heterochromatic more accessible or less accessible to TF? euchromatin? - less; more
if a cell has a hyperchromatic or condensed nucleus is it undergoing transcription etc? -
no
what are chromosomes? during what part of the cell cycle are they found? in what
pathologic state would you see a lot of chromosomes? - highly condensed forms of
DNA; mitosis; neoplasia- highly dividing and thus hyperchromatic
what experiment is chromosomes used for? - karyotyping
are histones in heterochromatin or euchromatin more methylated? which had more
acetylated histones? - heterochromatin; euchromatin
what does guanine have on it? - a ketone
what does thymine have on it? - a methyl
deamination of what pyrimidine makes what? - cytosine to uracil
in what genetic code is uracil found in? in replace of what? - uracil; thymine
how many bonds does a G-C connection have? what type of bonds? how about a A-T?
- 3 hydrogen bonds; 2 hydrogen bonds
what amino acids are required in purine synthesis? which of these does pyrimidine
synthesis require also? - glutamine, aspartate, glycine; aspartate
what is the difference between a nucleotide and a nucleoside? - nucleoside is just the
ribose plus the base; nucleotide is the ribose plus the base but the phosphate bond
Is PRPP added later or first in pyrimidine synthesis? - later
,what is PRPP? how is it made? - its the ribose; its made from PRPP synthetase using
ribose 5 P from the HMP shunt
what is the precursor for both purines? - IMP
what is the precursor for pyrimidines? - orotate
which intermediate is involved in both pyrimidine synthesis and the urea cycle? -
carbamoyl phosphate
why does a deficiency in ornithine transcarbamoylase (urea cycle enzyme) result in an
increased production of orotic acid, the pyrimidine precursor? - because carbamaoyl
phosphate is involved in both urea cycle and pyrimidine synthesis
is CPSII or CPSI involved in pyrimidine synthesis? - CPSII
what three enzymes lead to orotic acid accumulation? what reactions are they involved
in? - ortinithine transcarbamoylase, orotic acid phosphoribosyltransferase, and orotidine
5 phosphate decarboxylase; urea cycle; last two are involved in conversion of orotic
acid to UMP (adding PRPP to orotic acid)
what step in pyrimidine synthesis requires aspartate? - carbamoyl phosphate to orotic
acid
what are the clinical symptoms of orotic aciduria? - increased orotic acid in urine,
megaloblastic anemia, +/- hyperammonemia
how do you differentiate the causes of orotic aciduria? - whether or not the patient is
also hyperammonemia (if yes, then OTC def)
how do you differentiate causes of megaloblastic anemia? - orotic aciduria
megaloblastic anemia can not be corrected with folic acid or vit B12
how do you treat orotic aciduria? how does this work? - oral uridine administration;
provides nucleosides and provides feedback inhibition
what converts dUMP to dTMP? what drug blocks this? - thymidylate synthase; 5-
Flourouracil
what drug blocks ribonucleotide reductase? what does this enzyme do? - hydroxurea;
deoxygenates ribose
what does ornithine transcarbamyolase do to carbamoyl phosphate? - converts it to
citrulline
what does 6 mercaptopurine do? - 6MP blocks de novo purine synthesis
,other than thymidylate synthase, what else is required to convert dUMP to dTMP? -
N5N10 methylene THF
After N5N10 methylene THF donates a methyl for conversion of dUMP to dTMP what is
it converted to? - DHF
what enzyme converts DHF to THF? what vitamin cofactor is used to transfer a methyl
from an amino acid to DHF? what amino acid is that? - dihydrofolate reductase; vitamin
B12; homocysteine
what happens to homocysteine after converting a methyl? - becomes methionine
how is THF converted to N5N10 Methylene? - using serine (which turns into glycine
after reaction)
what does methotrexate do? what step is this enzyme involved in? - it inhibits
conversion of DHF to THF by blocking dihyrdofolate reductase
what is the difference between methotrexate and trimethroprim? - trimethroprim inhibits
bacterial dihyrofolate reductase
what is adenosine/AMP converted to? through what enzyme? - inosine/IMP; adenosine
deaminase
GMP is degraded to guanosine which is degraded to guanine. What two options are
next? by what enzymes? - either salvage by HGPRT and PRPP or converstion to
xanthine and then to uric acid by xanthine oxidase
IMP is degraded to inosine and then to hypoxanthine. what two options are next? by
what enzymes? - either salvage by HGPRT and PRPP or conversion to xanthine and
then uric acid by xanthine oxidase
in what syndrome is HGPRT deficient? what is the inheritance pattern? - Lesch Nyhan
syndrome; X linked recessive
what is main lab finding in Lesch Nyhan syndrome? due to what enzyme deficiency?
what reaction is deficient? - uric acidemia; HGPRT; purine salvage
what are the main clinical symptoms of Lesch Nyhan syndrome? - self mutilation,
aggression, mental retardation, gout, hyperuricemia, choreathetosis
what is the major cause of SCID? what does SCID stand for? - adenosine deaminase
deficiency; Severe combined immunodeficiency disease
, what is the link between adenosine deaminase deficiency and decreased lymphocyte
count? - excess ATP and dATP has negative feedback inhibition on ribonucleotide
reductase which results in decreased DNA synthesis and thus decreased lymphocyte
count
what has negative feedback inhibition on ribonucleoside reductase? - ATP and dATP
what is methotrexate? - a folic acid analogue
what is given to prevent side effects when methotrexate is given? why does this work? -
folinic acid; does not require DHF
in the genetic code, what does unambiguous mean? - each codon specifies only one
amino acid
what does degenerate/redundant mean in terms of the genetic code? - codons may
encode same amino acid since there are only ~20 aa
what structures allows for degeneracy? - tRNA wobble
what is the exception to degeneracy in the genetic code? - methionine is only encoded
by AUG
what is the exception to the nonoverlapping/commaless aspect of the genetic code? -
some viruses
what is the exception to the universal aspect of the genetic code? - mitochondria,
archaebacteria, mycoplasma, and some yeasts
what are the three types of point mutations? - silent, misssense, nonsense
what is a clinical example of a missense mutation? - sickle cell disease- conversion of
hydroophillic glutamic acid to hyrdophobic valine
what is an example of a nonsense mutation? - beta thalassemia
what creates a frameshift mutation? what are some clinical examples? - insertion or
deletion of a number of nucleotides indivisible by 3; tay sachs, duchennes MD
what does topoisomerase do? I or II eukaryotic? - creates nicks in DNA to prevent
supercoiling; both!
what is DNA gyrase? - a topoisomerase II
what Ab class blocks DNA gyrase? - Flouroquinolones
