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USMLE 1 Biochem


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What changes a cytosine into a uracil?
a Deaminase
Which base nucleotides contain an extra amino group?

Which base nucleotide has an extra methyl group?

(THYmine = meTHYl)
What are the purines?

Purines: Adenine & Guanine
(PURe As Gold)

Pyrimidines: Cytosine, Uracil & Thymine
(CUT the Py)
How does Methyltrexate work on DNA?
prevents changing a uracil to a thymine
If a sample of DNA has 10% G, how much is the T %?
10% G + 10% C = 20%

therefore 80%/2 = 40% T
Which DNA has a higher melting point?


Define melting point.
CG bonds
They have a triple H-bond

Melting point = 50% double-stranded & 50% single-stranded DNA
What is the charge of Histones?

What 2 AA are histones abundant in?

Arginine & Lysine
what causes chromatin to be tightly packaged?

Name of this type of chromatin? (active or inactive)

If it is not packed tightly, what is it sensitive to?

Heterochromatin - inactive

Endonuclease activation and chromatin fragmentation are characteristic of cell death by apoptosis. What nucleic cell structure would most likely be degraded first in an apoptotic cell?
10 nm fiber

(this is the chromosome without the H-1; fiber b/t a nucleosome)
number of origins the prokaryote and eukaryote can begin with regarding DNA replication?
Pro - one

Eu - many
What is the same structure in DNA and RNA synthesis?
both require a DNA template
Something that helps attach nucleotides via a PDE bond to make a new nucleic acid

(Polymer = glue)
What is needed to begin DNA synthesis?

RNA synthesis?
DNA: RNA primer

RNA: nothing
What has the ability to proofread DNA?

How and in what direction?
DNA polymerase III

3' -> 5' Exonuclease
What recognizes the Origin of replication in a prokaryotic and eukaryotic cell?
Prokaryotic: DNA A protein

Eukaryotic: nothing
Unwinds DNA in Prokaryotic and eukaryotic cells?

What does it require?

(requires ATP)
What stabilizes unwound template strands of DNA?

(Single-stranded DNA-binding protein)
What synthesizes RNA primers?
Responsible for synthesis of Leading strand of DNA in the prokaryotic cell?

Eukaryotic cell?
Pro: DNA polymerase III

Eu: DNA polymerase Delta
Responsible for synthesis of Lagging strand of DNA in the prokaryotic and eukaryotic cell?
Pro: DNA polymerase III

Eu: DNA polymerase Alpha
What is responsible for the REMOVAL of RNA primers in prokaryotic cells?
In what direction/activity?
Pro: DNA poly I
5' -> 3' exonuclease activity
What is responsible for replacement of RNA primer w/ DNA?
DNA poly I
Joins Okazaki fragments
DNA ligase
Removes positive supercoils ahead of advancing replication forks?
DNA topoisomerase II
Synthesis of telomers in prokaryotic and eukaryotic cells?
Pro: not required (circular)

Eu: Telomerase
What requires an RNA template to direct the synthesis of new DNA?
RNA-dependent DNA polymerase

(Reverse Transcriptase)
DNA repair have two main enzymes that do all the REPAIR work...what are they?
DNA polymerase

DNA ligase
What excises thymine dimers?
Excision endonuclease
What phase of cell cycle does a mismatch base problem occur?

What phase is it fixed?
Occurs: S

Fixed: G2
What is used to proofread human DNA?
3' -> 5' Exonuclease activity of DNA poly Delta
What do each of the (3) eukaryotic RNA polymerases make?
RNA poly I: rRNA

RNA poly II: mRNA, hnRNA

RNA poly III: tRNA, 5S rRNA
What DNA strand should you assume the boards mean if it is not labeled?
Coding strand

(strand you will build a template strand from)
During RNA synthesis, the DNA template sequence TAGC would be transcribed to produce which of the following sequences?

(always write in 5'->3' direction)
What initiates the promoter in the prokaryotic cell?

What may be required to terminate transcription?
intiate: Sigma

terminate: Rho + stem & loop
(or UUUUU + stem & loop)
What is the initiation codon on the CODING strand of a transcription unit?

(corresponding to AUG RNA)
What does the promoter consist of in a prokaryotic cell?

What is the "number" of the starting site?
(-35) sequence & (-10) TATAAT

starting site: +1
What does the promoter consist of in a eukaryotic cell?

What binds the promoter?
(-70) CAAT + (-25 TATA box)

Transcription Factors
What is the portion just before the initiation codon of a prokaryotic cell called?
What recognizes this?
Shine-Dalgarno sequence

16S RNA of prokaryotic ribosome
What is the term referred to as the creation of a single protein?

What type of cell does this?

(polycistronic is prokaryotic)
3 posttranscriptional processing steps for eukaryotics
1. 5' Cap (7-MeG)

2. 3' poly-A tail

3. removing interons w/ splicesome
where does transcription and translation occur in the eukaryotic cell?
transcription - nucleus

translation - cytoplasm


Transition - purine for purine

Transversion - purine for pyrmidine
Mutation type in DNA that creates a new codon
Mutation type in DNA that creates a stop codon
3 stop codons
UGA (U Go Away)

UAA (U Are Away)

UAG (U Are Gone)
What type of genetic problem is caused by a deletion or addition of a single base?
Frameshift mutation
blood problem that is a result of a large segment deletion
blood problem that is the result of a splicing of the donor or acceptor sites (beginning of interons/exons)
What is responsible for accuracy of the amino acid selection along with tRNA?

what is needed to activate this?

2 high-energy ATP bonds
What does the UCG anti-codon code for?

(remember to read anti-codon backwards: 5'->3')
What is the bond between two amino acids called?

Where does this form?
peptide bond

occurs in the ribosome
What is the anti-codon for the start codon?
What site in the rRNA does the tRNA bring the AA to?

What amount of energy is needed to translate a protein?
A-site (acceptor)

Describe the 4 levels of protein shape
Primary - Amino Acids

Secondary - folded AA into a-helix or b-sheet

Tertiary - 3-D the secondary structures

Quarternary - multiple subunits (ex - Hb: 2a2b)
Why is there "rough" ER?
N-terminus (NH2) of newly translated protein is hydrophobic, so the rRNA will move to and attach to the ER to complete translation within the ER
What does the golgi do to the new protein?
adds sugars to the N-terminus
What AA does the golgi add N-oligosaccharides to?

O-oligosaccharides? (2)*
N: Asparagine

O: Serine and Threonine
What does the golgi do if it wants to send the new protein to the lysosomes?
Adds Mannose-6-Phosphate via phosphotransferase
protein creation problem that accompanies the signs of coarse facial features, gingival hyperplasia, joint immobility, growth/psychomotor retardation, cardioresp failure in first decade.

What is missing in protein creation?
Dx: I-cell disease

(can't send proteins to lysosomes)
2 cells rich in RER
Goblet cells of the GI

Ab-secreting Plasma cells
What cell organelle is responsible for steroid synthesis?

What else is it responsible for?
Smooth ER

also responsible for: detoxification of drugs and poisons
Covalent modification to proteins by adding 2 negative charges to allow calcium to bind.

What important function uses this method?

What drug prevents this?

Clotting factors 2, 7, 9, 10

(Warfarin prevents gamma-carboxy)
Most prevalent AA in collagen?

Two other common AA in collagen?

Proline & Lysine
Where does hydroxylation of preprocollagen occur?

What is hydroxylated?

What cofactor is needed for it to occur?
Proline & Lysine are hydroxylated in the ER

Vitamin C is required
What occurs to collagen after it is hydroxylated?
In what part of the cell?

What is formed here?
Glycosylated in Golgi

Triple helix (Procollagen)
Following glycosylation of collagen, what is the next step and alteration of the structure?

What is it now called?
Procollagen is secreted from the cell.
Then terminal ends are cleaved.

Then called: Tropocollagen
What is needed to make the tropocollagen into fibrils and stabilizes this structure?
Lysyl Oxidase & Copper
(4)* Collagen synthesis deficiencies

1. Scurvy
2. Osteogenesis Imperfecta
3. Menkes Dz
3. Ehlers-Danlos
Petechiae, ecchymoses, bleeding gums, poor wound healing, poor bone development


hydroxylation of collagen deficiency secondary to lack of Vit-C
Skeletal abnormalities, multiple fractures, blue sclera
Osteogenesis Imperfecta
Hyperextensible, fragile skin, hypermobile joints, vericose veins, arterial and intestinal ruptures


Lysine hydroxylase collagen deficiency secondary to lack of copper
To compare collagen counts of several tissues, what could be measured?
hydroxyproline or hydroxylysine

(not Glycine--b/c it's prevalent in other tissues)
6 month infant has fractured rib; subdural hematoma; thin, colorless, tangled hair; low serum copper; developmental delay.

What enzyme is deficient?
Menkes disease

Lysyl Oxidase in collagen metabolism, which requires copper
What do pseudomonas and diphtheria toxins inhibit in eukaryotic translation?
eEF-2: translocation factor
What sequence is found at the 3' end of the tRNA?
CCA then the Amino acid
What intermediate is formed by the splicing of the interons out of the mRNA transcripts?

What facilitates the splicing?
Lariat-shaped intermediate

snRNA ("Snurp") facilitates
With the lac opeon, what is on/off if only glucose is present?

Only Lactose?


When is Z, Y, A made?
Glucose: Repressor-ON; CAP-OFF

Lactose: Repressor-OFF; CAP-ON (Z, Y, A, made)

Both: Repressor-OFF; CAP-OFF

(glucose causes CAP off and Lactose causes Repressor off)
What favors gene expresson--histone acetylases or deacetylases?

histone acetylases - open hisones

anything that condenses or bulks chromatin does not favor gene expression
Where are enhancers located?
may be upstream, downstream or within interon of gene they control (due to looping)
When you see "zinc fingers", "leucine zippers", or "helix-loop-helix", what are they talking about?

What are the fingers?

(steroid receptors are fingers, while cAMP response elements are zippers)
If you have multiple abnormalities with a single gene point mutation, where is the mutatuion?
HOX or PAX gene
childhood obesity and hyperphagia, hypogonadotrophic hypogonadism, small hands and feet, mental retardation, hypotonia

Type of genetic problem?
Prader-Willi syndrome

Genetic Imprinting
(father's gene only)
mental retardation, continuous laughing

Type of genetic problem?
Angelman syndrome
"Happy Puppet syndrome"

Genetic Imprinting
(mother's gene only)
What does bacteria do to protect its DNA?

How does it destroy foreign DNA (bacteriophage)?
it Methylates its DNA

Restriction endonucleases
What do restriction endonucleases recognize in the sequence?
Library made from nuclear DNA and is good for seeing all sequences in the cell.

Which library is good for seeing proteins (exons) without introns?
Genomic Libraries

cDNA Libraries
Example of a key tissue for collagen types 1-4
Bone SCAB:
I: bone, Skin
II: Cartilage
III: Arteries
IV: Basement membrane (4 to the floor)
What is a key feature to a Dominant genetic problem in pedigree (vs. recessive)?
Dominant - every generation is affected
(not in recessive)
What is a key feature to Autosomal genetic problem in pedigree (vs. X-linked)?
Autosomal - Male-to-male inheritance
(x-linked has no male-to-male)
Lateral displacement of the innercorner of the eye; Pigment abnormalities; congenital deafness; limb abnormalities

What gene is the problem?
Klein-Waardenburg Syndrome

HOX gene abnormality
If cystic fibrosis patient were to be treated with gene therapy, which type of cells should be targeted by the host cells?
Epithelial cells
name 5 Autosomal Dominant diseases
Familial Hypercholesterolemia;
Acute Intermittent Porphyria;
What is usually the common problem in the Autosomal Dominant diseases?
Structural protein damage
name 4 common Autosomal Recessive diseases
Sickle cell;
Cystic Fibrosis;
What type of genetic diseases affect energy production?
(Name 3)
Mitochondrial Diseases:

Leber's optic neuropathy;
name 4 X-linked recessive common diseases
Duchennes muscular dystrophy;
Hemophilia A & B
Paternal relationships b/t man and infant can best be determined by DNA fingerprinting. What about the DNA is analyzed?
Tandem repeats
2 amino acids that are the precursors for catecholamines

What NT does tryptophan form? What vitamin?

3 branched-chained amino acids found in Maple Syrup Urine disease?
I Love Vermont:

name the (6)* nonpolar, non-aromatic hydrophobic amino acids

Valine; Isoleucine; Proline

Glycine; Alanine; Leucine
Only amino acid with a phenol group?
name the 3 aromatic amino acids


the amino acid that acts as a methyl donor
name 3 amino acid that are basic

What is the pK of the R groups?

Histidine (6.5)
Lysine (10)
Arginine (13)
name the 2 amino acids that are acidic
What is the pK of the R groups?
Glutamate (4)

Aspartate (4)
What are the 2 pKs that every amino acid has?
pk (COO-) = 2

pk (NH2) = 9
What is the net charge on the amino acid if the pH is less then the pI?
What is the pI?
average of the pKs:

(2+9)/2 = 5.5 for normal AA

[average the 2 closest numbers for charged AA]
Main extracellular buffer
10 essential amino acids

What 2 essential amino acids are required during periods of growth?

What is the sign of delta G in a spontaneous reaction?
Affect on Km & Vmax:

1) Competitive Inhibitor

2) Non-competative Inh
Km= Increase; Vmax= no change

Km= no change; Vmax= Decrease
what does the x and y axis measure on Lineweaver-burke plots?

How does affinity relate to Km?
low Km = high Affinity
amino acid precursor to GABA
Glutamic Acid
amino acid precursor to Heme
the amino acid that is the precursor for:
Nitric Oxide
adds a phosphate to a substance
2 serine kinases

which receptor type has no g-protein and results in smooth muscle relaxation?

Second messenger?

Protein kinase G
What phosphorylates in the insulin/glucagon world?

Which needs ATP?
Glucagon - phosphorylates
(needs ATP)

Insulin - de-phosphorylates
removes a phosphate from a substance
What bug affects ADP-ribosylation at Gs receptors?

What bug affects it at Gi?

What do they both cause in the cell?
stimulates Gs- Cholera
(stimulates the stimulator)

inhibits Gi- Pertussis
(inhibits the inhibitor)

Both cause: Increase in cAMP
What two Vitamins can be used in dehydrogenase reactions?
Riboflavin (B2)

Niacin (B3)
Vitamin that makes CoA?
Pantothenic Acid (B5)
What (4)* things does the liver produce in a well-fed state?
Bile (from cholesterol)
What is the first step in a well-fed state for the following tissues: liver, RBC, brain, muscle, fat?
2 actions of RBC in a well-fed and fasting state?
1) glycolysis (for ATP)

2) Lactate production
What tissues use insulin receptors: GLUT 1 and 3?

What tissues use receptor: GLUT 2?
What tissues use receptor: GLUT 4?

Once there is enough energy in liver during well-fed state, what 2 substances build-up?

What is done with them?
Glucose & Acetyl-CoA

Glucose - added together to be stored as glycogen

Acetyl-CoA - added together to become fatty acids (then transported to adipose via VLDL)
What does adipose do during well-fed states?
takes in glucose and fatty acids to make ATP and fat
What (4)* substances enter the liver during a well-fed state? Where is each from?
Goes to Liver And Grows:

Glucose - food (blood)

Lactate - RBC

Amino Acids - food (blood)

Glycerol - Chylomicrons (food)
What does the liver give to tissues during fasting states?
To what tissues?
Glucose - RBC & Brain

Ketone bodies - muscle
What does muscle get during the fasting state?

From where?
Ketone bodies - liver
(once enough ATP is made and Aceytl-CoA builds-up)

Fatty acids - Adipose
(carried on albumin)
What does the muscle provide to the liver during fasting states?

For what?
Amino Acids

1. to make Pyruvate (then glucose)

2. for Urea cycle
2 sources (& preliminary substances) to make pyruvate b/t meals for the liver to make glucose
RBC - lactate

muscle - Alanine
What 2 ways can the GLUT-4 receptor move to the surface of muscle?
1) Increased Insulin

2) Exercise
What are the 2 anaerobic steps of substrate level phosphorylation in glycolysis?
1,3BPG --> 3PG
(via Phosphoglycerate kinase)

PEP --> Pyruvate
(via Pyruvate kinase)
What are two essential items needed to make ATP from NADH?
1) Oxygen

2) Mitochondria (for ETC)
What 2 steps of glycolysis use ATP?
First and third step:

Glucose --> G6P
(via Hexokinase/Glucokinase)

F6P --> F-1,6-BP
(via PFK-1)
What is the rate-limiting step of glycolysis?
Net ATP?

2 ATP (net)
How does the RBC replenish NADH?

With what essential enzyme?

If enzyme was not there, what would occur?
Pyruvate --> Lactate
(Enzyme: Lactate DH)

changes NAD+ --> NADH for glycolysis (lactate goes to liver)

If Lactate DH not there, RBC would die
What enzyme of glycolysis is only in the liver and is induced by insulin?

Level of affinity of this enzyme?

Low affinity = High Km = high Vmax
How is PFK-1 controlled?

Which form is active (dephosphorylated or phosphorylated)?
Insulin (dephos) stimulates PFK-2 for:
F6P --> F-2,6-BP
to make PFK-1

Glucagon (phosphorylates) inhibits PFK-2
What (3)* metabolic events occur in the mitochondria?
Fatty acid oxidation

Acetyl-CoA production

TCA cycle
What (5)* metabolic events occur in the cytoplasm?
Glucose Found Here Protects Steroids:
Fatty acid synthesis
HMP shunt
Protein synthesis (RER)
Steroid synthesis
What (3)* metabolic events occur in both the mitochondria and the cytoplasm?
Heme synthesis

Urea cycle

What 2 shuttles take NADH from the cytoplasm to the mitochondria?

How many ATP does each yield?

Which yields a FADH2 instead of the NADH in the mito?
Malate/OAA Shuttle - 3ATP

G3P Shuttle - 2ATP
(creates FADH2)
If a patient has cataracts early in life, what is the underlying metabolic problem?
What toxic substance accumulation causes this?
Galactose metabolism

Toxic: Galacititol
young patient with hepatosplenomegaly, cataracts, mental retardation.

Which enzyme presents sx at birth?
Which in early childhood?

Galactose-1-P uridyltransferase = at birth;

Galactokinase = early childhood
lethargy, vomiting, liver damage, hyperbilirubinemia, hypoglycemia, jaundice, renal proximal tubule problems.

What enzyme is deficient?
Fructose Intolerance

Aldolase B
What are the (5)* cofactors used for Pyruvate Dehydrogenase?
TLC For Nipples:
Thiamine (B1)
Lipoic Acid
Coenzyme A (B5)
FADH2 (B2)
What does Pyruvate DH change pyruvate into?
Acetyl CoA
Overall net reaction of the TCA cycle?

What makes the ATP in this reaction?
Acetyl CoA --> 2 CO2

3NADH + FADH2 + GTP = 12 ATP
(2x everything per one glucose)
Which enzyme in the TCA cycle is in the inner mitochondrial membrane versus the matrix of the mitochondria?
Succinate Dehydrogenase
What enzyme has the same 5 cofactors as Pyruvate DH?
Alpha-Ketogluterate DH
In order, what are the 8 steps in the TCA cycle?
Can I Keep Selling Sex For Money Officer?

Citrate-->Isocitrate--> (alpha)Ketogluterate--> Succinyl CoA-->Succinate--> Fumarate-->Malate-->OAA
What does a Pyruvate DH deficiency lead to?

What can it be due to?

How is it treated?
Lactic Acidosis
(from backup of substrates)

Seen in Alcoholics (thiamine deficiency)

Tx: Ketogenic acids
(Lysine & Leucine)
What part of the TCA cycle is also part of the ETC?
What does it provide to the ETC?
Succinate Dehydrogenase
(Complex II)

Provides: FADH2
What part of the TCA cycle deals with Fatty Acid synthesis?
What part of the TCA cycle deals with Heme synthesis?
Succinyl CoA
What part of the TCA cycle deals with the Urea cycle?
What parts of the TCA cycle deals with Gluconeogenesis?
OAA & Malate
What is the rate limiting step of the TCA cycle?

What does it depend on?
Isocitrate DH

depends on NADH levels
What enzymes in the TCA produce the energy?
Ketoglutarate DH - NADH
Isoglutarate DH - NADH
Malate DH - NADH
Succinyl CoA - GTP
Succinate DH - FADH2
What does Complex I use in ETC?

What drug class inhibits Complex I?

What 3 reactions add FADH2 to Coenzyme Q?

Which is considered Complex II?
TCA (Succinate DH)
[Complex II]

Glycerol-P shuttle

Beta-oxidation (Fatty Acyl CoA DH)
Which Complex in the ETC uses Oxygen?

Another name for thtis complex?

What else is needed for this Complex?

What 2 compounds inhibit this Complex?
Complex IV (Cyto a/a3)


Cyanide & CO
Where is the ATP made in the ETC?

What inhibits this?
ATP Synthase

What is a common Uncoupler?

How does it work?

Brings H+ across the proton gradient, which inhibits the creation of ATP and increases Oxygen consumption
What is the rate limiting step in Glycogen creation?
UDP-Glucose --> Glycogen
(via Glycogen Synthase)
In which type of muscle fiber is glucose converted to Lactate?

In which type is it completely oxidized?
to Lactate:
White (fast) fibers

completely oxidized:
Red (slow) fibers
What converts Glycogen back into Glucose 1-P?

What stimulates it in the liver and muscle?
(2 each