Mastering Biochemistry: Your Ultimate Guide to
USMLE Step 1 Success
A Comprehensive Exam Study Guide With 100%
Verified Questions and Answers.
Latest Updated Exam Study Guide 2025/2026.
which histone ties DNA-histone nucleosome beads into more condensed structures? - ansH1
is DNA acidic or basic? - ansacidic
what type of aa are histones made of? are they acidic or basic? - anslysine and arginine; basic
is heterochromatic more accessible or less accessible to TF? euchromatin? - ansless; more
if a cell has a hyperchromatic or condensed nucleus is it undergoing transcription etc? - ansno
what are chromosomes? during what part of the cell cycle are they found? in what pathologic
state would you see a lot of chromosomes? - anshighly condensed forms of DNA; mitosis;
neoplasia- highly dividing and thus hyperchromatic
what experiment is chromosomes used for? - anskaryotyping
are histones in heterochromatin or euchromatin more methylated? which had more acetylated
histones? - ansheterochromatin; euchromatin
what does guanine have on it? - ansa ketone
what does thymine have on it? - ansa methyl
deamination of what pyrimidine makes what? - anscytosine to uracil
in what genetic code is uracil found in? in replace of what? - ansuracil; thymine
how many bonds does a G-C connection have? what type of bonds? how about a A-T? - ans3
hydrogen bonds; 2 hydrogen bonds
what amino acids are required in purine synthesis? which of these does pyrimidine synthesis
require also? - ansglutamine, aspartate, glycine; aspartate
what is the difference between a nucleotide and a nucleoside? - ansnucleoside 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? - anslater
what is PRPP? how is it made? - ansits the ribose; its made from PRPP synthetase using
ribose 5 P from the HMP shunt
what is the precursor for both purines? - ansIMP
what is the precursor for pyrimidines? - ansorotate
which intermediate is involved in both pyrimidine synthesis and the urea cycle? -
anscarbamoyl phosphate
why does a deficiency in ornithine transcarbamoylase (urea cycle enzyme) result in an
increased production of orotic acid, the pyrimidine precursor? - ansbecause carbamaoyl
phosphate is involved in both urea cycle and pyrimidine synthesis
is CPSII or CPSI involved in pyrimidine synthesis? - ansCPSII
what three enzymes lead to orotic acid accumulation? what reactions are they involved in? -
ansortinithine 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? - anscarbamoyl phosphate to orotic acid
what are the clinical symptoms of orotic aciduria? - ansincreased orotic acid in urine,
megaloblastic anemia, +/- hyperammonemia
how do you differentiate the causes of orotic aciduria? - answhether or not the patient is also
hyperammonemia (if yes, then OTC def)
how do you differentiate causes of megaloblastic anemia? - ansorotic aciduria megaloblastic
anemia can not be corrected with folic acid or vit B12
,Mastering Biochemistry: Your Ultimate Guide to
USMLE Step 1 Success
A Comprehensive Exam Study Guide With 100%
Verified Questions and Answers.
Latest Updated Exam Study Guide 2025/2026.
how do you treat orotic aciduria? how does this work? - ansoral uridine administration;
provides nucleosides and provides feedback inhibition
what converts dUMP to dTMP? what drug blocks this? - ansthymidylate synthase; 5-
Flourouracil
what drug blocks ribonucleotide reductase? what does this enzyme do? - anshydroxurea;
deoxygenates ribose
what does ornithine transcarbamyolase do to carbamoyl phosphate? - ansconverts it to
citrulline
what does 6 mercaptopurine do? - ans6MP blocks de novo purine synthesis
other than thymidylate synthase, what else is required to convert dUMP to dTMP? -
ansN5N10 methylene THF
After N5N10 methylene THF donates a methyl for conversion of dUMP to dTMP what is it
converted to? - ansDHF
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? - ansdihydrofolate reductase; vitamin B12;
homocysteine
what happens to homocysteine after converting a methyl? - ansbecomes methionine
how is THF converted to N5N10 Methylene? - ansusing serine (which turns into glycine after
reaction)
what does methotrexate do? what step is this enzyme involved in? - ansit inhibits conversion
of DHF to THF by blocking dihyrdofolate reductase
what is the difference between methotrexate and trimethroprim? - anstrimethroprim inhibits
bacterial dihyrofolate reductase
what is adenosine/AMP converted to? through what enzyme? - ansinosine/IMP; adenosine
deaminase
GMP is degraded to guanosine which is degraded to guanine. What two options are next? by
what enzymes? - anseither 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? - anseither 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? - ansLesch Nyhan
syndrome; X linked recessive
what is main lab finding in Lesch Nyhan syndrome? due to what enzyme deficiency? what
reaction is deficient? - ansuric acidemia; HGPRT; purine salvage
what are the main clinical symptoms of Lesch Nyhan syndrome? - ansself mutilation,
aggression, mental retardation, gout, hyperuricemia, choreathetosis
what is the major cause of SCID? what does SCID stand for? - ansadenosine deaminase
deficiency; Severe combined immunodeficiency disease
what is the link between adenosine deaminase deficiency and decreased lymphocyte count? -
ansexcess 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? - ansATP and dATP
what is methotrexate? - ansa folic acid analogue
,Mastering Biochemistry: Your Ultimate Guide to
USMLE Step 1 Success
A Comprehensive Exam Study Guide With 100%
Verified Questions and Answers.
Latest Updated Exam Study Guide 2025/2026.
what is given to prevent side effects when methotrexate is given? why does this work? -
ansfolinic acid; does not require DHF
in the genetic code, what does unambiguous mean? - anseach codon specifies only one amino
acid
what does degenerate/redundant mean in terms of the genetic code? - anscodons may encode
same amino acid since there are only ~20 aa
what structures allows for degeneracy? - anstRNA wobble
what is the exception to degeneracy in the genetic code? - ansmethionine is only encoded by
AUG
what is the exception to the nonoverlapping/commaless aspect of the genetic code? - anssome
viruses
what is the exception to the universal aspect of the genetic code? - ansmitochondria,
archaebacteria, mycoplasma, and some yeasts
what are the three types of point mutations? - anssilent, misssense, nonsense
what is a clinical example of a missense mutation? - anssickle cell disease- conversion of
hydroophillic glutamic acid to hyrdophobic valine
what is an example of a nonsense mutation? - ansbeta thalassemia
what creates a frameshift mutation? what are some clinical examples? - ansinsertion or
deletion of a number of nucleotides indivisible by 3; tay sachs, duchennes MD
what does topoisomerase do? I or II eukaryotic? - anscreates nicks in DNA to prevent
supercoiling; both!
what is DNA gyrase? - ansa topoisomerase II
what Ab class blocks DNA gyrase? - ansFlouroquinolones
what is bleomycin? - ansan anti cancer agent that is a topoisomerase II and creates nicks in
DNA
what is etoposide? why does this not affect normal healthy cells? - ansa topoisomerase II
inhibitor; because cancer cells use II more so than healthy cells
what type of polymerase is primase? - ansDNA dependent RNA polymerase
what type exonuclease activity does DNA polymerase III have? in what organisms is it
found? - ans3'--> 5'; prokaryote only
what type of exonuclease activity does DNA polymerase I have? in what organisms is it
found? what is it used for? - ans5'--> 3'; prokaryote only; for removing RNA primer and
filling it with DNA
what type of drug are alkylating agents? how do they work? give a couple examples -
ansantineoplastic agents; alkylate DNA!; cyclophosphamide and nitrosurea (aka lomustrine-
a nitrosource)
what two anti-neoplastic drugs work by blocking DNA and RNA polymerase? -
ansdactinomycin, doxorubicin
name two antineoplastic drugs that work by inhibiting the mitotic spindle by MT blocking. -
ansvincrstine (vinca alkaloids) and paclitaxel
how are senescent cells different from some neoplastic and germ cells? what does this
substance do? - anstelomerase; an RNA polymerase that uses a RNA template to add DNA to
the end of shortening 3' ends
, Mastering Biochemistry: Your Ultimate Guide to
USMLE Step 1 Success
A Comprehensive Exam Study Guide With 100%
Verified Questions and Answers.
Latest Updated Exam Study Guide 2025/2026.
what four enzymes are required for nucleotide excision repair? - ansendonucleases,
exonucleases, DNA polymerase, DNA ligase
what is the difference between exonucleases and endonucleases? - ansendonucleases are
specific and break specific linking phosphodiester bonds, exonucleases are not sequence
specific and just remove the nucleoside
what type of enyzmes are used in base excision repair? - ansglycosylases (only remove the
base- cut the bond between ribose and base)
what is needed after the glycosylase in base excision repair? - ansan AP (apyrimidinic)
endonuclease to cut the DNA, exonuclease then removes and then filled and sealed by
enzymes
what is most often mutated in xeroderma pigmentosum? what is the inheritance pattern? what
are the clinical symptoms? - ansUV specific endonucleases for excision repair; AR; dry skin,
photosensitivity, poikiloderma, susceptibility to skin cancers
to what type of DNA damage are xeroderma pigmentation susceptible to? - ansUV
nonionizing radiation causing thymidine dimers
how does mismatch repair work? in what cancer is it mutated? what type of DNA is
methylated? - ansimmediately after replication, DNA is unmethylated and so it is a signal to
be double checked; HNPCC; heterochromatin
what kind of DNA damage does ionizing radiation cause? what type of repair helps with this?
- ansdouble strand breaks; nonhomologous end joining
which end carries the triphosphate? which end of DNA makes the hydoxyl attack? - ans5'
end; 3' end
what aa does AUG mRNA code for in eukaryotes? prokaryotes? - ansmethionine; f Met
(formyl methyl methionine)
what is the difference between the promoter and enhancer? in what process are they used for?
- anspromoter binds RNA Pol II and is very close (25 bases) to initiation site and is AT rich;
enhancer/silencers bind TFs only, can be located close or far and regulate gene expression but
not specifically initiation; transcription
what do enhancers/silencers bind? - ansTFs
do RNA polymerases have proofreading function? what does this mean for HIV? - ansno;
increased mutation rate!
which RNA polymerase synthesizes tRNAs and snRPs? - ansIII
which RNA polymerase synthesizes rRNA? where? - ansI; nucleolus
how many RNA polymerases do prokaryotes have? what drug blocks prokaryotic RNA
polymerase only? what is it used for? - ans1 for all three classes of RNA; Rifampin; TB
What toxin causes liver failure by inhibiting RNA polymerase II if ingested? where does it
come from? - ansalpha amanitin; mushroom caps
what three steps are included in RNA processing? where does it occur? - ans5' capping (with
7 methylguanosine), 3' adenylation, splicing of introns; nucleus
what is the signal for adenylation? what enzyme does? does it require a template? -
ansAAUAAA; Poly A polymerase; no
what is the RNA called before processing? and after? - anshnRNA; mRNA
what are required for splicing? encoded by what polymerase? - anssnRNPs; RNA polymerase
III
USMLE Step 1 Success
A Comprehensive Exam Study Guide With 100%
Verified Questions and Answers.
Latest Updated Exam Study Guide 2025/2026.
which histone ties DNA-histone nucleosome beads into more condensed structures? - ansH1
is DNA acidic or basic? - ansacidic
what type of aa are histones made of? are they acidic or basic? - anslysine and arginine; basic
is heterochromatic more accessible or less accessible to TF? euchromatin? - ansless; more
if a cell has a hyperchromatic or condensed nucleus is it undergoing transcription etc? - ansno
what are chromosomes? during what part of the cell cycle are they found? in what pathologic
state would you see a lot of chromosomes? - anshighly condensed forms of DNA; mitosis;
neoplasia- highly dividing and thus hyperchromatic
what experiment is chromosomes used for? - anskaryotyping
are histones in heterochromatin or euchromatin more methylated? which had more acetylated
histones? - ansheterochromatin; euchromatin
what does guanine have on it? - ansa ketone
what does thymine have on it? - ansa methyl
deamination of what pyrimidine makes what? - anscytosine to uracil
in what genetic code is uracil found in? in replace of what? - ansuracil; thymine
how many bonds does a G-C connection have? what type of bonds? how about a A-T? - ans3
hydrogen bonds; 2 hydrogen bonds
what amino acids are required in purine synthesis? which of these does pyrimidine synthesis
require also? - ansglutamine, aspartate, glycine; aspartate
what is the difference between a nucleotide and a nucleoside? - ansnucleoside 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? - anslater
what is PRPP? how is it made? - ansits the ribose; its made from PRPP synthetase using
ribose 5 P from the HMP shunt
what is the precursor for both purines? - ansIMP
what is the precursor for pyrimidines? - ansorotate
which intermediate is involved in both pyrimidine synthesis and the urea cycle? -
anscarbamoyl phosphate
why does a deficiency in ornithine transcarbamoylase (urea cycle enzyme) result in an
increased production of orotic acid, the pyrimidine precursor? - ansbecause carbamaoyl
phosphate is involved in both urea cycle and pyrimidine synthesis
is CPSII or CPSI involved in pyrimidine synthesis? - ansCPSII
what three enzymes lead to orotic acid accumulation? what reactions are they involved in? -
ansortinithine 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? - anscarbamoyl phosphate to orotic acid
what are the clinical symptoms of orotic aciduria? - ansincreased orotic acid in urine,
megaloblastic anemia, +/- hyperammonemia
how do you differentiate the causes of orotic aciduria? - answhether or not the patient is also
hyperammonemia (if yes, then OTC def)
how do you differentiate causes of megaloblastic anemia? - ansorotic aciduria megaloblastic
anemia can not be corrected with folic acid or vit B12
,Mastering Biochemistry: Your Ultimate Guide to
USMLE Step 1 Success
A Comprehensive Exam Study Guide With 100%
Verified Questions and Answers.
Latest Updated Exam Study Guide 2025/2026.
how do you treat orotic aciduria? how does this work? - ansoral uridine administration;
provides nucleosides and provides feedback inhibition
what converts dUMP to dTMP? what drug blocks this? - ansthymidylate synthase; 5-
Flourouracil
what drug blocks ribonucleotide reductase? what does this enzyme do? - anshydroxurea;
deoxygenates ribose
what does ornithine transcarbamyolase do to carbamoyl phosphate? - ansconverts it to
citrulline
what does 6 mercaptopurine do? - ans6MP blocks de novo purine synthesis
other than thymidylate synthase, what else is required to convert dUMP to dTMP? -
ansN5N10 methylene THF
After N5N10 methylene THF donates a methyl for conversion of dUMP to dTMP what is it
converted to? - ansDHF
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? - ansdihydrofolate reductase; vitamin B12;
homocysteine
what happens to homocysteine after converting a methyl? - ansbecomes methionine
how is THF converted to N5N10 Methylene? - ansusing serine (which turns into glycine after
reaction)
what does methotrexate do? what step is this enzyme involved in? - ansit inhibits conversion
of DHF to THF by blocking dihyrdofolate reductase
what is the difference between methotrexate and trimethroprim? - anstrimethroprim inhibits
bacterial dihyrofolate reductase
what is adenosine/AMP converted to? through what enzyme? - ansinosine/IMP; adenosine
deaminase
GMP is degraded to guanosine which is degraded to guanine. What two options are next? by
what enzymes? - anseither 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? - anseither 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? - ansLesch Nyhan
syndrome; X linked recessive
what is main lab finding in Lesch Nyhan syndrome? due to what enzyme deficiency? what
reaction is deficient? - ansuric acidemia; HGPRT; purine salvage
what are the main clinical symptoms of Lesch Nyhan syndrome? - ansself mutilation,
aggression, mental retardation, gout, hyperuricemia, choreathetosis
what is the major cause of SCID? what does SCID stand for? - ansadenosine deaminase
deficiency; Severe combined immunodeficiency disease
what is the link between adenosine deaminase deficiency and decreased lymphocyte count? -
ansexcess 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? - ansATP and dATP
what is methotrexate? - ansa folic acid analogue
,Mastering Biochemistry: Your Ultimate Guide to
USMLE Step 1 Success
A Comprehensive Exam Study Guide With 100%
Verified Questions and Answers.
Latest Updated Exam Study Guide 2025/2026.
what is given to prevent side effects when methotrexate is given? why does this work? -
ansfolinic acid; does not require DHF
in the genetic code, what does unambiguous mean? - anseach codon specifies only one amino
acid
what does degenerate/redundant mean in terms of the genetic code? - anscodons may encode
same amino acid since there are only ~20 aa
what structures allows for degeneracy? - anstRNA wobble
what is the exception to degeneracy in the genetic code? - ansmethionine is only encoded by
AUG
what is the exception to the nonoverlapping/commaless aspect of the genetic code? - anssome
viruses
what is the exception to the universal aspect of the genetic code? - ansmitochondria,
archaebacteria, mycoplasma, and some yeasts
what are the three types of point mutations? - anssilent, misssense, nonsense
what is a clinical example of a missense mutation? - anssickle cell disease- conversion of
hydroophillic glutamic acid to hyrdophobic valine
what is an example of a nonsense mutation? - ansbeta thalassemia
what creates a frameshift mutation? what are some clinical examples? - ansinsertion or
deletion of a number of nucleotides indivisible by 3; tay sachs, duchennes MD
what does topoisomerase do? I or II eukaryotic? - anscreates nicks in DNA to prevent
supercoiling; both!
what is DNA gyrase? - ansa topoisomerase II
what Ab class blocks DNA gyrase? - ansFlouroquinolones
what is bleomycin? - ansan anti cancer agent that is a topoisomerase II and creates nicks in
DNA
what is etoposide? why does this not affect normal healthy cells? - ansa topoisomerase II
inhibitor; because cancer cells use II more so than healthy cells
what type of polymerase is primase? - ansDNA dependent RNA polymerase
what type exonuclease activity does DNA polymerase III have? in what organisms is it
found? - ans3'--> 5'; prokaryote only
what type of exonuclease activity does DNA polymerase I have? in what organisms is it
found? what is it used for? - ans5'--> 3'; prokaryote only; for removing RNA primer and
filling it with DNA
what type of drug are alkylating agents? how do they work? give a couple examples -
ansantineoplastic agents; alkylate DNA!; cyclophosphamide and nitrosurea (aka lomustrine-
a nitrosource)
what two anti-neoplastic drugs work by blocking DNA and RNA polymerase? -
ansdactinomycin, doxorubicin
name two antineoplastic drugs that work by inhibiting the mitotic spindle by MT blocking. -
ansvincrstine (vinca alkaloids) and paclitaxel
how are senescent cells different from some neoplastic and germ cells? what does this
substance do? - anstelomerase; an RNA polymerase that uses a RNA template to add DNA to
the end of shortening 3' ends
, Mastering Biochemistry: Your Ultimate Guide to
USMLE Step 1 Success
A Comprehensive Exam Study Guide With 100%
Verified Questions and Answers.
Latest Updated Exam Study Guide 2025/2026.
what four enzymes are required for nucleotide excision repair? - ansendonucleases,
exonucleases, DNA polymerase, DNA ligase
what is the difference between exonucleases and endonucleases? - ansendonucleases are
specific and break specific linking phosphodiester bonds, exonucleases are not sequence
specific and just remove the nucleoside
what type of enyzmes are used in base excision repair? - ansglycosylases (only remove the
base- cut the bond between ribose and base)
what is needed after the glycosylase in base excision repair? - ansan AP (apyrimidinic)
endonuclease to cut the DNA, exonuclease then removes and then filled and sealed by
enzymes
what is most often mutated in xeroderma pigmentosum? what is the inheritance pattern? what
are the clinical symptoms? - ansUV specific endonucleases for excision repair; AR; dry skin,
photosensitivity, poikiloderma, susceptibility to skin cancers
to what type of DNA damage are xeroderma pigmentation susceptible to? - ansUV
nonionizing radiation causing thymidine dimers
how does mismatch repair work? in what cancer is it mutated? what type of DNA is
methylated? - ansimmediately after replication, DNA is unmethylated and so it is a signal to
be double checked; HNPCC; heterochromatin
what kind of DNA damage does ionizing radiation cause? what type of repair helps with this?
- ansdouble strand breaks; nonhomologous end joining
which end carries the triphosphate? which end of DNA makes the hydoxyl attack? - ans5'
end; 3' end
what aa does AUG mRNA code for in eukaryotes? prokaryotes? - ansmethionine; f Met
(formyl methyl methionine)
what is the difference between the promoter and enhancer? in what process are they used for?
- anspromoter binds RNA Pol II and is very close (25 bases) to initiation site and is AT rich;
enhancer/silencers bind TFs only, can be located close or far and regulate gene expression but
not specifically initiation; transcription
what do enhancers/silencers bind? - ansTFs
do RNA polymerases have proofreading function? what does this mean for HIV? - ansno;
increased mutation rate!
which RNA polymerase synthesizes tRNAs and snRPs? - ansIII
which RNA polymerase synthesizes rRNA? where? - ansI; nucleolus
how many RNA polymerases do prokaryotes have? what drug blocks prokaryotic RNA
polymerase only? what is it used for? - ans1 for all three classes of RNA; Rifampin; TB
What toxin causes liver failure by inhibiting RNA polymerase II if ingested? where does it
come from? - ansalpha amanitin; mushroom caps
what three steps are included in RNA processing? where does it occur? - ans5' capping (with
7 methylguanosine), 3' adenylation, splicing of introns; nucleus
what is the signal for adenylation? what enzyme does? does it require a template? -
ansAAUAAA; Poly A polymerase; no
what is the RNA called before processing? and after? - anshnRNA; mRNA
what are required for splicing? encoded by what polymerase? - anssnRNPs; RNA polymerase
III
