Molecular EC Flashcards
Which is transcriptionally active: heterochromatin or euchromatin?
Euchromatin is active
HeteroChromatin is Highly Condenced
What do DNA methylation and acetylation do?
Methylation makes DNA Mute (inactive)
Acetylation makes DNA Active
What amino acids are required for purine synthesis?
GAG
Glycine, Aspartate, Glutamine
What does ribonucleotide reductase do?
reduces nucleotides to deoxy forms
What cofactors are required for ribonucleotide reductase action?
thioredoxin and NADPH
*oxidized thioredoxin reduced/recycled by tioredoxin reductase
What is the rate limiting step of purine synthesis?
PRPP synthetase
*converts Ribose-5-P to PRPP
What ensures balance is maintained in purine synthesis? (2 things)
Cross regulation (GMP requires ATP and vice versa)
Each pathway has end-product inhibition
What is the rate-limiting step of pyrimidine synthesis?
CPS-II (formation of carbamoyl phosphate from CO2, glutamine and ATP)
What nucleotides is IMP a precursor to?
AMP and GMP
What nucleotides are UMP a precursor to?
CTP and TMP
What converts dUMP to dTMP?
Thymidylate synthase
What causes Orotic aciduria?
How does it present?
What is the treatment?
Defect in UMP synthase (converts orotic acid to UMP)
Presents as megaloblastic anemia UNRESPONSIVE to B12 or folate
Treat with lifetime uridine supplementation
What is the sequence from AMP to Uric acid?
AMP–>Adenosine–>Inosine–>Hypoxanthine–>Xanthine–> Uric acid
What is the sequence from GMP to Uric acid?
GMP–>Guanine–>Xanthine–>Uric acid
What is SCID?
What is its mechanism?
Severe Combined Immunodeficiency Disease
Adenosine deaminase deficiency (inability to convert adenosine to inosine)
- ATP/GTP imbalance inhibits ribonucleotide reductase
- prevents DNA synthesis
- decreased lymphocytes count
What is Lesch-Nyhan syndrome?
What is its mechanism?
What are the findings?
Absence of HGPRT (& thus purine salvage)
“He’s Got Purine Recovery Troubles”
Results in excess uric acid production
Retardation Self-mutilation Aggression Hyperurecemia/gout Choreoathetosis
What is a silent point DNA mutation?
a mutation that codes for the same amino acid
often a change in the 3rd a.a. (tRNA wobble)
What is a missense mutation?
Wrong amino acid but similar chemical structure
What is a Nonsense mutation?
Change resulting in easly STOP codon
“STOP the NONSENSE”
What is a frameshift mutation?
Misreading all nucleotides downstream
Where are the p53 and RB genes located?
p53 is on chromosome 17
RB is on chromosome 13
Describe Mismatch Repair
Mismatch repair enzymes recognize mismatched nucleotides
GATC endonuclease makes incision in daughter strand
Removed and gap filled
Mutations in mismatch repair enzymes gives rise to what disease?
HNPCC (hereditary nonpolyposal colorectal cancer)
Describe base excision repair
Cytosine is spontaneously deaminated to uracil
Uracil DNA glycosylase removes Uracil
AP endonucleases cut DNA and nucleotide is replaced
Describe nucleotide excision repair
thymidine dimmers caused by UV light are removed by excision endonucleases
What is Xeroderma pigmentosum
Caused by a mutation in excision endonucleases responsible for repairing thymidine dimers
Describe direct DNA repair
Alkylation agents (temozolide) cause methylation of Guanine.
MGMT repairs (permanently inactivated and can be depleted)
What is nonhomologous end joining?
Repair of double stranded DNA breaks
Caused by iodinizing radiation or free radical oxidation
Mutated in ataxia telangiectasia
What phase of the cell cycle to 5-FU and Methotrexate act?
What is the mechanism?
S-phase specific
Inhibit dTMP synthesis to block DNA replication
(5-FU inhibits thymidylate synthase)
(Methotrexate inhibits DHF reductase)
In what part of the cell cycle do Bleomycin and Etoposide act?
By what mechanism?
S and G2 phases
Inhibit topoisomerase II (preventing strand sepparation)
What is the mechanism of Cyclophosphamide and Nitosoureas?
Alkylating agents that lead to copying errors and expression of abnormal proteins
What is the mechanism of Doxorubicin and Actinomycin D?
Intercalated into DNA rand block DNA/RNA polymerases
What phase of the cell cycle do vinca alkaloids (vincristine and paclitaxel) work?
What are their mechanisms?
M-phase specific
Vincristine inhibits mitotic spindle formation
Paclitaxel inhibits mitotic spindle breakdown
BCL2 proto oncogene function and associated tumors
Inhibits apoptosis
Mutated in follicular B cell lymphoma
ERBB2 proto oncogene function and associated tumors
Binds epidermal growth factor
Breast
Ovarian
Stomach
MYC proto oncogene function and associated tumors
Activates transcription
Burkitt’s Lymphoma
Neuroblastoma
RAS proto oncogene function and associated tumors
G protein that transducers growth factor signals
Bladder
Lung
Colon
Pancreas
APC tumor suppressor gene function and associated tumors
Inhibits MYC expression
FAP (familial Adenomatous Polyposis)
Colorectal cancer
BRCA1 and BRCA2 tumor suppressor gene function and associated tumors
DNA repair
BRCA1 Breast Ovary Colon Prostate
BRCA2
Male and female breast
NF1 and NF2 tumor suppressor gene function and associated tumors
Control intra cellular signaling
Neurofibromatosis: optic nerve gliomas, meningioma, acoustic neuroma, pheochromocytoma
TP53 tumor suppressor gene function and associated tumors
Mediates G1 arrest and apoptosis
Li-Fraumeni Breast Brain Leukemia Sarcoma
RB1 tumor suppressor gene function and associated tumors
Mediates G1 arrest
Retinoblastoma
Osteosarcoma
Breast cancer
WT1 tumor suppressor gene function and associated tumors
Represses transcription in developing kidney
Wilm’s tumor
Ataxia telangiectasia
Defective DNA repair (double stranded breaks)
Lymphoma
Cerebellar ataxia; dilation of blood vessels in skin and eyes
Immunodeficiency (B and T cells)