What enzyme does the following drug inhibit in nucleotide synthesis? 1. Leflunomide 2. Mycophenolate, Ribavirin 3. Hydroxyurea 4. 6-Mercaptopurine (MP) and its prodrug Azathioprine 5. 5-Fluorouracil (5-FU) 6. Methotrexate (MTX), Trimethoprim (TMP), and pyrimethamine

1. dihydroorotate dehydrogenase 2. IMP dehydrogenase 3. ribonucleotide reductase 4. de novo purine synthesis 5. thymidylate synthase 6. dihydrofolate reductase

Biochemistry - Molecular Flashcards by Robin Sautter

What is the structure of chromatin?

“Beads on a string”

Negative DNA wrapped around a positively charged histone octamer –> forms a nucleosome

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What phase does DNA and histone synthesis occur?

S phase

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Which type of chromatin is condensed and which is less condensed b/t heterochromatin and euchromatin?

Heterochromatin - highly condensed, transcriptionally inactive

Euchromatin - less condensed, transcriptionally active

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At what site does DNA methylation occur?

What is a result of DNA methylation?

CpG islands

Methylated CpG islands repress transcription

“CpG Methylation Makes DNA Mute”

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Histone methylation

Histone Methylation Mostly Makes DNA Mute

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What effect does histone acetylation have on DNA?

Relaxes DNA coiling –> allows transcription

Histone Acetylation makes DNA Active

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What are the 2 purines? How many rings do they have?

Adenine, Guanine (PURe As Gold)

2 rings

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What are the 3 pyrimidines? How many rings do they have?

Cytosine, Thymine, Uracil (CUT the PY (pie))

1 ring

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What structure is uracil found in?
What structure is thymine found in?

DNA vs. RNA

RNA

DNA

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What side group does thymine have?

A methyl group

Thymine has a methyl.

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What amino acids are necessary for purine synthesis?

GAG

Glycine
Aspartate
Glutamine

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NucleoSide = base (deoxy)ribose

Attached to a SUGAR

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NucleoTide = base (deoxy)ribose + phosphaTe

Linked by 3’-5’ phosphodiester bond

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Which two metabolic pathways is carbamoyl phosphate involved in?

pyrimidine synthesis

urea cycle

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What enzyme does the following drug inhibit in nucleotide synthesis?

Leflunomide
Mycophenolate, Ribavirin
Hydroxyurea
6-Mercaptopurine (MP) and its prodrug Azathioprine
5-Fluorouracil (5-FU)
Methotrexate (MTX), Trimethoprim (TMP), and pyrimethamine

dihydroorotate dehydrogenase
IMP dehydrogenase
ribonucleotide reductase
de novo purine synthesis
thymidylate synthase
dihydrofolate reductase

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Purine Salvage Deficiencies

What disease results from a deficiency in adenosine deaminase?

What is its genetic inheritance pattern?

What molecular findings will you see?

SCID

Autosomal recessive

Excess ATP and dATP –> prevents DNA synthesis –> decreases lymphocyte count

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Purine Salvage Deficiencies

What disease results from a deficiency in HGPRT?

What is its genetic inheritance pattern?

What molecular findings will you see?

What physical findings will you see?

What is the treatment?

Lesch-Nyhan Syndrome

X-linked recessive

Overproduction of purines and accumulation of uric acid
Hypersegmented neutrophils*

Intellectual disability, gout, dystonia

Tx: allopurinol or febuxostat (2nd line)

Hyperuricemia
Gout
Pissed off (aggression, self-mutilation e.g. biting nails)
Retardation (intellectual disability)
DysTonia (spasticity)

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Which two codons are encoded only by 1 codon (AUG and UGG, respectively)?

Methionine and tryptophan

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What type of DNA replication occurs in both prokaryotes and eukaryotes?

Semi-conservative DNA replication

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How many origins of replication does a prokaryote have? Eukaryote?

1) single

2) multiple

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What is the function of a helicase enzyme?

unwinds DNA

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What is the function of a single-stranded binding protein?

prevent strands from reannealing

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What is the function of a DNA topoisomerase?

What drug class inhibits DNA gyrase (prokaryotic topoisomerase II)?

Create a single or double stranded break in the helix to add or remove supercoils
Fluoroquinolones

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What is the function of a primase?

make an RNA primer on which DNA polymerase III can initiate replication

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What two polymerases are present in prokaryotes only?

DNA polymerase I and II

In what direction is DNA made?

5' --> 3'

What is the function of DNA polymerase I?

Degrades RNA primer --> replaces it w/ DNA

What is the function of DNA ligase?

Joins Okazaki fragments together on lagging strand

What is the function of telomerase?

RNA dependent DNA polymerase that adds DNA to 3' ends of chromosomes to avoid loss of genetic material w/ every duplication

What is the order of severity of mutations in DNA from least to most?

silent << missense < nonsense < frameshift

For silent, missense, and nonsense mutations, what are the changes made to the DNA?

Transition: purine --> purine (e.g. A to G) or pyrimidine to pyrimidine (e.g. C to T) Transversion: purine to pyrimidine (e.g. A to T) or vice versa

What is a silent mutation?

nucleotide substitution but codes for same amino acid *often base change in 3rd position of codon (tRNA wobble)

What is a missense mutation?

nucleotide substitution --> changed amino acid (conservative if similar in chemical structure) *Sickle Cell Disease

What is a nonsense mutation?

nucleotide substitution --> early STOP codon STOP the NONSENSE!

What is a frameshift mutation?

Deletion or insertion of a number of nucleotides not divisible by 3 --> misreading of all nucleotides downstream --> truncation or non-functional protein e.g. Duchenne Muscular Dystrophy

What is nucleotide excision repair (NER)? Is it a single or double strand repair?

Specific endonucleases release the oligonucleotide-containing damaged bases DNA polymerase and ligase fill and reseal the gap Repairs bulky helix-distorting lesions Single strand repair

What disease arises from a defect in nucleotide excision repair (NER)?

Xeroderma pigmentosum

What is base excision repair? For what is BER especially important for repairing?

Base-specific glycosylase recognizes altered base --> DNA polymerase-beta fills the gap --> DNA ligase seals it Important in repair of spontaneous/toxic deamination

What is mismatch repair (MMR)?

Newly synthesized strand is recognized --> mismatched nucleotides removed --> gap filled and resealed

What disease arises from a defect in MMR?

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

What is non homologous end joining?

Bringing together 2 ends of DNA fragments to repair double-stranded breaks No requirement for homology

What disease arises from a defect in non homologous end joining?

Ataxia telangiectasia

DNA and RNA are both synthesized in what direction?

5' --> 3' direction

mRNA is read in what direction?

5' --> 3' direction

What mRNA codon starts protein synthesis

AUG

What are the mRNA stop codons?

``` UGA = U Go Away UAA = U Are Away UAG = U Are Gone ```

What does a promoter do?

Site where RNA polymerase and multiple other TFs bind to DNA upstream from gene locus (TATA box)

What happens if there is a mutation in the promoter?

Dramatic decrease in level of gene transcription

What is the function of enhancers and silencers?

Enhancers - stretch of DNA that alters gene expression by binding transcription factors Silencers - site where negative regulators (repressors) bind

What kind of mRNA does RNA polymerase I make?

rRNA (most numerous RNA, rampant)

What kind of mRNA does RNA polymerase II make?

mRNA (largest RNA, massive)

What kind of mRNA does RNA polymerase III make?

tRNA (smallest RNA, tiny)

What is the process for making heterogenous nuclear RNA (hnRNA) into mRNA?

1. capping of 5' end (addition of 7-methylguanosine cap) 2. polyadenylation of 3' end (~200 A's) 3. splicing out of introns

Where in the cell is mRNA translated?

cytosol

What are the 3 steps to splicing pre-mRNA?

1. primary transcript contains small nuclear ribonucleoproteins (snRNPs) to form spliceosome 2. Lariat-shaped loop is made 3. Lariat is released to remove INTRONS and join 2 exons

Abs to spliceosomal snRNPs are associated with which disease? What are they also called?

Anti-Smith Abs | Associated with SLE

Anti-U1 RNP Abs are highly associated with which disease?

mixed connective tissue disease

What is the fate of introns? Exons?

Introns are intervening sequences and say in the nucleus (introns are spliced OUT!) Exons exit and are expressed.

Abnormal splicing variants are implicated in what diseases?

Oncogenesis and genetic disorders (e.g. beta-thalassemia)

What ensures accuracy of amino acid selection with tRNA?

1. aminoacyl-tRNA synthetase | 2. binding of charged tRNA to the codon

What is the tRNA wobble?

Accurate base pairing only required in first 2 nucleotide positions of an mRNA codon so codons differing in 3rd "wobble" position

What are the 3 stages of protein synthesis?

1. Initiation 2. Elongation 3. Termination

Describe the process of initiation...

Initiated by GTP hydrolysis Initiation factors help assemble the 40S ribosomal subunit with the initiator tRNA and are released when the mRNA and the ribosomal 60S subunit assemble with the complex

What are the subunits from eukaryotes and prokaryotes?

Eukaryotes: 40S + 60S --> 80S (EVEN) PrOkaryotes: 30S + 50S --> 70S (ODD)

What is the order for elongation of a synthesizing protein?

Think of "going APE" A site = incoming Aminoacyl-tRNA P site = accommodates growing Peptide E site = holds Empty tRNA as it Exits

What causes termination of protein synthesis?

stop codon is recognized by a release factor

What are some post translational modifications?

trimming | covalent alterations

What does a chaperone protein do?

intracellular protein involved in facilitating and/or maintaining protein folding

Biochemistry - Molecular Flashcards

(68 cards)