,USMLE Step 1 Biochemistry Mega Guide
2025 | 350+ High-Yield Q&A | Graded A+ &
Verified/USMLE Step 1 Biochem Study Pack
| Enzyme Pathways, Diseases, Vitamins,
Metabolism | A+ Notes.
Heterochromatin
Highly Condensed DNA
Transcriptionally inactive
Ex. Barr bodies (inactivated X chromosomes)
Euchromatin
Less condensed DNA
Transcriptionally active
DNA Methylation
Occurs at CpG Islands to repress transcription
'CpG Methylation Makes DNA MUTE'
Template strand cytosine and adenine are methylated, which allow mismatch repair enzymes to
distinguish between old and new strands.
Histone Methylation
Represses DNA transcription
Histone Acetylation
Relaxes DNA coiling and allows for transcription
'Histone acetylation makes DNA ACTIVE'
Histones
Nucleosome (8):
-H2A x2
-H2B x2
-H3 x2
-H4 x2
Linker Histone
-H1
,Histones rich in arginine and lysine
Purines vs Pyrimidines
Purines: A, G (2 rings)
Pyrimidines: T, C (1 ring)
G-C bond has 3 H bonds (higher melting temperature)
A-T bond has 2 H bonds
Pyrimidine Synthesis Rate Limiting Step
Carbamoyl Phosphate Synthetase II
Combines Glutamine, CO2, ATP to make Carbamoyl Phosphate
Purine Synthesis Rate Limiting Step
Glutamine PRPP Aminotransferase
Converts PRPP to IMP
Lesch-Nyhan Syndrome
Defective purine salvage due to absent HGPRT
Unable to recycle Guanine and Hypoxanthine to GMP and IMP respectively.
Excess Uric acid and de novo purine synthesis
HGPRT: hyperuricemia. gout, pissed off (aggression, self mutilation), retardation, dysTonia
Helicase
Unwinds DNA template at replication fork
Single Stranded binding proteins
prevent strands from reannealing
DNA Topoisomerases
Creates single or double stranded break in helix to remove supercoils
T1: No ATP required
T2: ATP required
Primase
Makes RNA primer for DNA polymerase III to initiate transcription
, DNA Polymerase III
Prokaryotes ONLY
Lays down new strand in 5' to 3' direction (synthesis)
and has 3' to 5' exonuclease activity (proof reading)
DNA Polymerase I
Degrades RNA primer and replaces it with DNA
DNA Ligase
Joins Okazaki fragments
Telomerase
Eukaryotes ONLY
Adds DNA to 3' end of chromosomes to avoid loss of genetic material
Silent Mutation
Nucleotide substitution codes for same amino acid
(Synonymous)
Missense Mutation
Nucleotide substitution results in changed amino acid
Nonsense Mutation
Nucleotide substitution results in early stop codon
Frameshift Mutation
Deletion or insertion (not divisible by 3) resulting in misreading of all nucleotides downstream.
Usually results in truncated, non functional protein
Lac Operon
Low Glucose: increased adenylyl cyclase activity, increase cAMP, activating CAP (catabolite activator
protein) and causes transcription
High Lactose: unbinds repressor protein from repressor/operator site and allows for increased
transcription
Start Codons
AUG
Codes for methionine in eukaryotes
2025 | 350+ High-Yield Q&A | Graded A+ &
Verified/USMLE Step 1 Biochem Study Pack
| Enzyme Pathways, Diseases, Vitamins,
Metabolism | A+ Notes.
Heterochromatin
Highly Condensed DNA
Transcriptionally inactive
Ex. Barr bodies (inactivated X chromosomes)
Euchromatin
Less condensed DNA
Transcriptionally active
DNA Methylation
Occurs at CpG Islands to repress transcription
'CpG Methylation Makes DNA MUTE'
Template strand cytosine and adenine are methylated, which allow mismatch repair enzymes to
distinguish between old and new strands.
Histone Methylation
Represses DNA transcription
Histone Acetylation
Relaxes DNA coiling and allows for transcription
'Histone acetylation makes DNA ACTIVE'
Histones
Nucleosome (8):
-H2A x2
-H2B x2
-H3 x2
-H4 x2
Linker Histone
-H1
,Histones rich in arginine and lysine
Purines vs Pyrimidines
Purines: A, G (2 rings)
Pyrimidines: T, C (1 ring)
G-C bond has 3 H bonds (higher melting temperature)
A-T bond has 2 H bonds
Pyrimidine Synthesis Rate Limiting Step
Carbamoyl Phosphate Synthetase II
Combines Glutamine, CO2, ATP to make Carbamoyl Phosphate
Purine Synthesis Rate Limiting Step
Glutamine PRPP Aminotransferase
Converts PRPP to IMP
Lesch-Nyhan Syndrome
Defective purine salvage due to absent HGPRT
Unable to recycle Guanine and Hypoxanthine to GMP and IMP respectively.
Excess Uric acid and de novo purine synthesis
HGPRT: hyperuricemia. gout, pissed off (aggression, self mutilation), retardation, dysTonia
Helicase
Unwinds DNA template at replication fork
Single Stranded binding proteins
prevent strands from reannealing
DNA Topoisomerases
Creates single or double stranded break in helix to remove supercoils
T1: No ATP required
T2: ATP required
Primase
Makes RNA primer for DNA polymerase III to initiate transcription
, DNA Polymerase III
Prokaryotes ONLY
Lays down new strand in 5' to 3' direction (synthesis)
and has 3' to 5' exonuclease activity (proof reading)
DNA Polymerase I
Degrades RNA primer and replaces it with DNA
DNA Ligase
Joins Okazaki fragments
Telomerase
Eukaryotes ONLY
Adds DNA to 3' end of chromosomes to avoid loss of genetic material
Silent Mutation
Nucleotide substitution codes for same amino acid
(Synonymous)
Missense Mutation
Nucleotide substitution results in changed amino acid
Nonsense Mutation
Nucleotide substitution results in early stop codon
Frameshift Mutation
Deletion or insertion (not divisible by 3) resulting in misreading of all nucleotides downstream.
Usually results in truncated, non functional protein
Lac Operon
Low Glucose: increased adenylyl cyclase activity, increase cAMP, activating CAP (catabolite activator
protein) and causes transcription
High Lactose: unbinds repressor protein from repressor/operator site and allows for increased
transcription
Start Codons
AUG
Codes for methionine in eukaryotes
