Biochemistry: First Aid USMLE Step 1
latest well elaborated
What is a nucleoside?
What is a nucleotide?
Which are the purines?
Which are the pyrimidines? - ANSWERSSide = base + (deoxy)ribose [sugar]
Tide = base + (deoxy)ribose [sugar] + phosphaTe
*Which are the purines?*
"pure as gold" = Adenosine, Guanosine
*Which are the pyrimidines?*
"CUT the pyramid" = Cytosine, Uracil, Thymine
In the nucleotide synthesis pathway, describe how purine synthesis differs from
pyrimidine synthesis.
Fr the following drugs, describe how they interfere with purine or pyrimidine synthesis.
Leflunomide
Methotrexatem Trimethoprim and Pyrimethamine
5-Fluorouracil
6-Mercaptopurine
Mycophenolate and Ribavirin
Hydroxyurea - ANSWERS*Disrupt pyrimidine synthesis*
*Leflunomide: *inhibits dihydroorate dehydrogenase
*Methotrexatem Trimethoprim and Pyrimethamine: inhibit dihydrofolate reductase,
resulting in decreased dTMP in humans, bacteria and protozoa respectively.
5-Fluorouracil*: inhibits thymidylate syhtnase
*Disrupt purine synthesis*
*6-Mercaptopurine* (6-MP): and its prodrug azathioprine inhibit de novo purine
synthesis
*Mycophenolate and Ribavirin*: inhibit inosine monophosphate dehydrogenase
*Disrupt purine and pyrimidine synthesis*
*Hydroxyurea*: inhibits nucleotide reductase
Adenosine deaminase deficiency
,*metabolic deficiency:*
*symptoms:* - ANSWERS*metabolic deficiency:*
- absence of adenosine deaminase resulting in increased dATP which is toxic to
lymphocytes
- one of the major causes of autosomal recessive SCID
*symptoms:*
Lesch-Nyhan Syndrome
*pattern of inheritance*:
*metabolic deficiency:*
*symptoms:* - ANSWERS*pattern of inheritance*:
- x-linked recessive
*metabolic deficiency:*
- defective purine salvage due to absence of HGPRT which converts hypoxanthine to
IMP and guanine to GMP
- this results in excess uric acid production and de novo purine synthesis
*symptoms:*
remember *HGPRT*
- Hyperuricemia
- Gout
- Pissed off (aggression)
- Retarded (intellectual disability)
- DsyTonia
Describe organization of eukaryotic DNA/gene - ANSWERSCoding strand : 5'
..Enhancer.............CAATbox(-75)....TATAA box(-25)....transcription start
site(+1)......exon....intron...exon.....AAATAAA..3'
-on exam always assume it's the 5'-3' coding strand that you see
-5'-3' coding strand (same as RNA)
-3'-5' template strand (compl. To RNA)
-5'-3' mRNA
-(CAAT & TATAA are the promoter region)
Regulation of gene expression - ANSWERS-Promoter - CAAT and TATA box region
upstream. RNA poly II and other transcription factors bind here.
-Enhancer -
- Silencer
What is the function of the following polymerases:
RNA Polymerase I
RNA Polymerase II
RNA Polymerase III
,Describe the processing of hmRNA to form an mRNA and where does this process
occur - ANSWERS
Lac operon - ANSWERSLow glucose: hi AC activity -> hi cAMP -> activation of CAP
induces transcription only if repressor is not bound
High lactose: unbinds repressor from the opersator and increases transcription
Nucleotide excision repair - ANSWERSexcision endonucleases release oligonucleotide
containing damaged bases. DNA polymerase fills in gap and ligase seals it. Repairs
bulky kelix-distortine lesions. Occurs in G1 phase. Defect in xoderma pigmentosum,
which prevents repair of pyrimidine dimers because of UV exposure
Base excision repair - ANSWERSBase specific glycosylases remove altered base and
creates AP site. One or more nucelotides are removed by AP endonucleases that
clease the 5' end, Lyase cleases the 3' end, and DNA poly 3 fillgs gap and ligase seals
it. ........... Important fo cytosine deamination and nitrates from meat?
Mismatch repair - ANSWERSNewly synthesized strand is recognized, mismatched
nucleotides are removed, and the gap is filled and resealed. Occurs in G2 phase
-MSH2 finds mismatch
-MCH1 takes it out
-Defective in Lynch syndrome (HNPCC)
*What is the splicing process of pre-mRNA?*
*What is the name for antibodies againsr splicesosome snRNPs and what disease are
they highly specific for?*
What disease are anti-UI RNP antibodies associated with?* - ANSWERS*What is the
splicing process of pre-mRNA?*
*What is the name for antibodies againsr splicesosome snRNPs and what disease are
they highly specific for?
- antibodies to spliceosomal snRNPS (aka *anti-SMITH antibodies) are highly specific
for SLE
*What disease are anti-UI RNP antibodies associated with?*
- mixed connective tissue disease
How do cyclins and tumor supressors regulate cell cycle - ANSWERSCDK -
Constitutive and inactive
Cyclin - activate CDKs
Cyclin-CDK complexes - phosphorylate other proteins to coordinate cell cycle
progression; must be activated and inactivated at appropriate times for cell cycle to
progress
, Tumor suppressor - p53 induces p21, which inhibits CDKs -> hypophos (activation) of
Rb -> hypophos Rb binds and inactivates E2F -> inhibit G1-S progression.
------Mutation in these genes recsult un unrestrained cell division (Li-frau)
Permanent cells - ANSWERS-Neurons, skeletal and cardiac muscle, RBC
-Remain in Go phase
Stabile (quiescent) cells - ANSWERS-Hepatocytes, lymphocytes
-Enter G1 from Go when stimulated
Labile cells - ANSWERS-Bone marrow, gut epithelium, skin, hair follicles, germ cells
-Never go to Go but rapidly divide
Cells rich in RER
Cells rich in SER - ANSWERSRER - mucus secreting goblet cells of small intesting and
antibody secreting plasma cells
SER - liver hepatocytes and steroid hormone-producing cells of the adrenal cortex and
gonads
I cell disease - ANSWERS-Inherited lysosomal storage disorder.
-Defect in phosphotransferase -> golgi cant phosphorylate manonose on glycoproteins
(low mannose 6 phosphate) -> proteins/hydrolytic enzymes cannot be transported to
lysosomes and is transported extracellularly -> generalized inflam
-Symptoms - coarse facial features, clouded corneas, restricted joint movement, high
plasma levels of lysosome enzymes
Kartagener syndrome - ANSWERS-aka primary ciliary diskynesia
-immotile cilia due to dynein arm defect.
-Symptoms - male and female infertility, bronchiectasis, recurrent sinnusitis, situs
inversus - know difference between this and CF
For the following types of collagen, name the tissues in which they are most commonly
found/important and any relevant diseases in which they are altered.
Type I
Type II
Type III
Type IV - ANSWERS
Osteogenesis imperfecta
*pattern of inheritance*:
*mutation:*
*symptoms:* - ANSWERS*pattern of inheritance*:
- genetic bone disorder (brittle bone disease)
latest well elaborated
What is a nucleoside?
What is a nucleotide?
Which are the purines?
Which are the pyrimidines? - ANSWERSSide = base + (deoxy)ribose [sugar]
Tide = base + (deoxy)ribose [sugar] + phosphaTe
*Which are the purines?*
"pure as gold" = Adenosine, Guanosine
*Which are the pyrimidines?*
"CUT the pyramid" = Cytosine, Uracil, Thymine
In the nucleotide synthesis pathway, describe how purine synthesis differs from
pyrimidine synthesis.
Fr the following drugs, describe how they interfere with purine or pyrimidine synthesis.
Leflunomide
Methotrexatem Trimethoprim and Pyrimethamine
5-Fluorouracil
6-Mercaptopurine
Mycophenolate and Ribavirin
Hydroxyurea - ANSWERS*Disrupt pyrimidine synthesis*
*Leflunomide: *inhibits dihydroorate dehydrogenase
*Methotrexatem Trimethoprim and Pyrimethamine: inhibit dihydrofolate reductase,
resulting in decreased dTMP in humans, bacteria and protozoa respectively.
5-Fluorouracil*: inhibits thymidylate syhtnase
*Disrupt purine synthesis*
*6-Mercaptopurine* (6-MP): and its prodrug azathioprine inhibit de novo purine
synthesis
*Mycophenolate and Ribavirin*: inhibit inosine monophosphate dehydrogenase
*Disrupt purine and pyrimidine synthesis*
*Hydroxyurea*: inhibits nucleotide reductase
Adenosine deaminase deficiency
,*metabolic deficiency:*
*symptoms:* - ANSWERS*metabolic deficiency:*
- absence of adenosine deaminase resulting in increased dATP which is toxic to
lymphocytes
- one of the major causes of autosomal recessive SCID
*symptoms:*
Lesch-Nyhan Syndrome
*pattern of inheritance*:
*metabolic deficiency:*
*symptoms:* - ANSWERS*pattern of inheritance*:
- x-linked recessive
*metabolic deficiency:*
- defective purine salvage due to absence of HGPRT which converts hypoxanthine to
IMP and guanine to GMP
- this results in excess uric acid production and de novo purine synthesis
*symptoms:*
remember *HGPRT*
- Hyperuricemia
- Gout
- Pissed off (aggression)
- Retarded (intellectual disability)
- DsyTonia
Describe organization of eukaryotic DNA/gene - ANSWERSCoding strand : 5'
..Enhancer.............CAATbox(-75)....TATAA box(-25)....transcription start
site(+1)......exon....intron...exon.....AAATAAA..3'
-on exam always assume it's the 5'-3' coding strand that you see
-5'-3' coding strand (same as RNA)
-3'-5' template strand (compl. To RNA)
-5'-3' mRNA
-(CAAT & TATAA are the promoter region)
Regulation of gene expression - ANSWERS-Promoter - CAAT and TATA box region
upstream. RNA poly II and other transcription factors bind here.
-Enhancer -
- Silencer
What is the function of the following polymerases:
RNA Polymerase I
RNA Polymerase II
RNA Polymerase III
,Describe the processing of hmRNA to form an mRNA and where does this process
occur - ANSWERS
Lac operon - ANSWERSLow glucose: hi AC activity -> hi cAMP -> activation of CAP
induces transcription only if repressor is not bound
High lactose: unbinds repressor from the opersator and increases transcription
Nucleotide excision repair - ANSWERSexcision endonucleases release oligonucleotide
containing damaged bases. DNA polymerase fills in gap and ligase seals it. Repairs
bulky kelix-distortine lesions. Occurs in G1 phase. Defect in xoderma pigmentosum,
which prevents repair of pyrimidine dimers because of UV exposure
Base excision repair - ANSWERSBase specific glycosylases remove altered base and
creates AP site. One or more nucelotides are removed by AP endonucleases that
clease the 5' end, Lyase cleases the 3' end, and DNA poly 3 fillgs gap and ligase seals
it. ........... Important fo cytosine deamination and nitrates from meat?
Mismatch repair - ANSWERSNewly synthesized strand is recognized, mismatched
nucleotides are removed, and the gap is filled and resealed. Occurs in G2 phase
-MSH2 finds mismatch
-MCH1 takes it out
-Defective in Lynch syndrome (HNPCC)
*What is the splicing process of pre-mRNA?*
*What is the name for antibodies againsr splicesosome snRNPs and what disease are
they highly specific for?*
What disease are anti-UI RNP antibodies associated with?* - ANSWERS*What is the
splicing process of pre-mRNA?*
*What is the name for antibodies againsr splicesosome snRNPs and what disease are
they highly specific for?
- antibodies to spliceosomal snRNPS (aka *anti-SMITH antibodies) are highly specific
for SLE
*What disease are anti-UI RNP antibodies associated with?*
- mixed connective tissue disease
How do cyclins and tumor supressors regulate cell cycle - ANSWERSCDK -
Constitutive and inactive
Cyclin - activate CDKs
Cyclin-CDK complexes - phosphorylate other proteins to coordinate cell cycle
progression; must be activated and inactivated at appropriate times for cell cycle to
progress
, Tumor suppressor - p53 induces p21, which inhibits CDKs -> hypophos (activation) of
Rb -> hypophos Rb binds and inactivates E2F -> inhibit G1-S progression.
------Mutation in these genes recsult un unrestrained cell division (Li-frau)
Permanent cells - ANSWERS-Neurons, skeletal and cardiac muscle, RBC
-Remain in Go phase
Stabile (quiescent) cells - ANSWERS-Hepatocytes, lymphocytes
-Enter G1 from Go when stimulated
Labile cells - ANSWERS-Bone marrow, gut epithelium, skin, hair follicles, germ cells
-Never go to Go but rapidly divide
Cells rich in RER
Cells rich in SER - ANSWERSRER - mucus secreting goblet cells of small intesting and
antibody secreting plasma cells
SER - liver hepatocytes and steroid hormone-producing cells of the adrenal cortex and
gonads
I cell disease - ANSWERS-Inherited lysosomal storage disorder.
-Defect in phosphotransferase -> golgi cant phosphorylate manonose on glycoproteins
(low mannose 6 phosphate) -> proteins/hydrolytic enzymes cannot be transported to
lysosomes and is transported extracellularly -> generalized inflam
-Symptoms - coarse facial features, clouded corneas, restricted joint movement, high
plasma levels of lysosome enzymes
Kartagener syndrome - ANSWERS-aka primary ciliary diskynesia
-immotile cilia due to dynein arm defect.
-Symptoms - male and female infertility, bronchiectasis, recurrent sinnusitis, situs
inversus - know difference between this and CF
For the following types of collagen, name the tissues in which they are most commonly
found/important and any relevant diseases in which they are altered.
Type I
Type II
Type III
Type IV - ANSWERS
Osteogenesis imperfecta
*pattern of inheritance*:
*mutation:*
*symptoms:* - ANSWERS*pattern of inheritance*:
- genetic bone disorder (brittle bone disease)
