Term
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Definition
Use: Antibiotic
Biochemistry: Acts on bacterial topoiserase II |
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Term
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Definition
Other Names: Cytoxan or Neosar
Use: Treatment of Hodgkin's lymphoma as well as certain lung, breast, and testicular cancers
Biochemistry: Pro-drug converted into active drug, phosphoramide mustard, in the liver. Bi-functional alkylating agent that forms inter- and intra-strand DNA crosslinks. Extensive damage blocks replication and can trigger programmed cell death |
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Term
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Definition
Other Names: Cytosar-U, Tarabine PFS
Use: Treatment of Acute Leukemia
Biochemistry: Analogue of Cytidine that contains arabinose in place of ribonose. Rapidly converted to cytarabine triphosphate inside cells which competes with DNT's for binding to DNA polymerase. Blocks DNA replication and repair. Other cytotoxic effects from incorporation of cytarabine into DNA and RNA |
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Term
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Definition
Other Names: Adriamyacin
Use: Broad activity against a variety of tumors
Biochemistry: Anthracycline antibiotic forms a tripartite complex with DNA and topoisomerase II. Binding interferes with catalytic cycle of topoisomerase II preventing religation of double stranded breaks. Programmed cell deaths due to excessive double-strand breaks |
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Term
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Definition
Use: Treatment for sickle cell anemia
Biochemistry: Stimulates expression of fetal copies of Betaglobin gene in adults that compensates for defective copy of gene |
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Term
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Definition
Use: Antibiotic
Biochemistry: Acts on bacterial topoisomerase II enzymes |
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Term
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Definition
Use: Antibiotic produced by streptomycetes found in soil
Biochemistry: Potent inhibitor of RNA polymerase found in a variety of bacteria. Eukarytic Pol II are unaffected by the drug.
Other: Particularly effective against Mycobacterium tuberculosis |
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Term
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Definition
Use: Treatment of breast cancers
Biochemistry: Some breast cancer cells contain estrogen receptors. Estrogen receptor/estrogen complex binds to DNA and recruits additional protein cofactors that activate transcription of estrogen-sensitive genes. Tamoxifen inhibits tumor growth by acting as a competitive inhibitor of the estrogen receptor. Complex binds to DNA, but fails to recruit additional factors needed to activate transcription. |
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Term
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Definition
Use: Antibiotic
Biochemistry: Binds to the small ribosomal subunit and inhibits initation. Also causes mistranslation of codons |
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Term
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Definition
Use: Antibiotic
Biochemistry: Binds to ribosomes and causes mistranslation of codons |
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Term
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Definition
Use: Antibiotic
Biochemistry: Binds to ribosomes and causes mistranslation of codons |
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Term
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Definition
Use: Antibiotic
Biochemistry: Blocks the A site of ribosomes and prevents tRNA binding |
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Term
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Definition
Use: Antibiotic
Biochemistry: Prevents the peptidyl bond formation |
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Term
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Definition
Other Names: Oncovin
Use: Treatment of retinoblastoma
Biochemistry: Microtubule inibitor |
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Term
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Definition
Use: Treatment of retinoblastoma
Biochemistry: alkylating agent, damages DNA |
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Term
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Definition
Other Names: Eposin,Etopophos, Vepesid, VP-16
Biochemistry: Inhibits topoisomerase II |
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Term
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Definition
Use: Tumor Suppressant
Biochemistry: Reverses hypermethylation, but targetting is difficult |
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Term
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Definition
Other Names: Gleevec
Use: Treats Philadelphia chromosome cancer or Chronic myeloid Leukemia
Biochemistry: Tyrosine kinase inhibitor that treats at receptor. Only works if due to issue with tyrosine kinase. If now a problem with Rb will not help. |
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Term
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Definition
Use: Treatment of non-small cell lung cancer
Biochemistry: Tyrosine Kinase inhibitor |
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Term
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Definition
Other Names: Trastuzumab
Use: Treatment of breast cancer
Biochemistry: Monoclonal antibody that bind HER2 (tyrosine kinase growth |
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Term
| Azoospermic Male (Meiosis Arrest) |
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Definition
• Symptoms
○ No sperm in the semen (azoospermia)
○ Normal germ cells, but no mature sperm cells
• Biochemistry
○ Failure to complete Meiosis I, no synaptonemal complex
Synaptonemal complex pairs chromosomal homologs |
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Term
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Definition
• Symptoms
○ Reduction in amount of hemogobin
○ Profound anemia
• Biochemistry
○ Reduced synthesis of the Beta-chain of hemoglobin
○ Hemoglobin consists of alpha and beta chains so amount of hemoglobin is reduced.
○ Beta0 mutation
§ Destroys normal acceptor site at the end of intron 2. To compensate, spliceosome uses a cryptic splice site downstream resulting in intron being incorporated into mRNA
○ Beta + mutation
§ Creates a new acceptor site in inron 1 causing the mRNA sequence to have an additional 19 nucleotides |
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Term
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Definition
ymptoms ○ Proportional dwarfism, keel-shaped face, photosensitive rash, immunodeficiency, reduced fertility, and a predisposition to the development of many types of malignancy
• Biochemistry
○ Mutations in the BLM gene
○ BLM encodes DNA helicase and cells from patients show defects in DNA replication, most notably delayed progression and processing of Okazaki fragments
○ Also disrupts homologous recombination events leading to chromosome instability |
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Term
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Definition
• Alpha-amanitin
• Symptoms
○ Gastrointestinal distress initially
○ After 48 hours, massive liver failure
• Biochemistry
○ Alpha-amanitin is inhibitor of Pol II which will block synthesis of mRNA
○ Essential liver proteins and their mRNAs degraded by hepatocyte mtabolism cannot be replaced by newly synthesized molecules
• Treatment
○ No antidote
○ Gastric lavage is performed and repeated doses of activated charcoal are administered to remove any unabsorbed toxin and interrupt enterohepatic circulation of toxin |
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Term
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Definition
• Molecules that fit exactly on the rungs o the DNA ladder, distorting the structure of the double helix.
• Acridine dyes (acridine orange), ethidium bromide, doxorubicin
• Mutagenic and cause insertions and deletions |
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Term
| Lynch Syndrome (HNPCC- Hereditatry Nonpolyposis Colorectal Carcinoma) |
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Definition
• Symptoms
○ Increased chance of developing colorectal cancer (80%)
○ Cancers of the stomach, small intestine, pancreas, kidney, ureter, and ovary may also develop
• Biochemistry
○ Defect in mismatch repair system
Vital in all cells so location-specificity of disease is puzzling |
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Term
| Rubinstein-Taybi Syndrome |
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Definition
• Symptoms
○ Mental retardation and other abnormalities
• Biochemistry
○ Point mutations, small deletions, and rearrangements within the genes encoding CBP or EP 300
CREB BP binds CREB and is a HAT, EP300 binds to phosphorylated CREB and is a transcription co-activator |
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Term
| Xeroderma pigmentosum (XP) |
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Definition
• Symptoms
○ Extreme sensitivity of the skin to sunlight, pigmentation changes, and skin cancers on areas of the body that are exposed to the sun
• Cause
○ Mutations that abolish or impair the function of proteins required for successful completion of nucleotide excision repair |
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Term
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Definition
• Symptoms
○ Rare form of cancer of the jaw found principally in African children
• Biochemistry
○ Majority of patients have a balanced translocation involving the myc protooncogene
§ t(8;14)(q24;q32)
○ Myc is translocated from normal cellular control mechanism and placed in close proximity to genes that encode immunoglobulin heavy, k light and d light chains
§ Causes large upregulation of myc in B cells driving cells into regulation |
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Term
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Definition
• Symptoms
○ 50% of carriers will develop malignancies by age 30
§ Sarcomas, osteosarcomas, brain tumors, breast or coon carcinomas, adrenal carcinomas and leukemia
○ 15% of individuals develop a second cander
• Cause
○ Often see mutations in p53
○ Autosomal dominant germ line mutation in p53
○ Mutated 53 will form tetramers causing it to be nonfunctional
§ Unable to stop cell division when DNA has been damaged or destroy cell by apoptosis
• Diagnosis
○ Sarcoma under age of 45, first degree relative with any cancer under 45 |
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Term
| Human Papilloma Virus (HPV) and Cervical Cancer |
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Definition
• Biochemistry
○ HPV produces E6 and E7 (early genes)
○ E6 inhibits p53
○ E7 inhibits p53, p21, and Rb |
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Term
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Definition
• Symptoms
○ Small reddish lesion at sight of injection, fever, and death after three days
• Biochemistry
○ Enzyme resistant against degradation can be taken up by cells and inactivate ribosomes (ingle molecule of ricin can inactivate 1500 ribosomes per minute)
○ Makes translation impossible
○ Glycosidase that removes the adenine bases from various positions of the rRNA in the large subunit
• Other information
○ Ricin is a protein that can be extractd from Castor beans and is used in bioterrorism. |
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Term
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Definition
• Biochemistry
○ Inactivates EF-2 by ADP-ribosylation
• Other Information
○ Protein produced by Corynebacterium diphtheria |
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Term
| Congenital Disorder of Glycosylation (CDG) |
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Definition
• Symptoms
○ Developmental delay and seizures, failure to thrive, hypotonia and ataxia, protein losing enteropathy, hypoglycemia
• Biochemistry
○ CDHs impair N-linked glycosylation of proteins
§ Very important to secreted and cell surface proteins
○ Failure to properly glycosylate these proteins will prevent their secretin and impair extracellular enzymatic reactions
• Diagnosis
○ Detecting the glycosylation status of transferrin, an abundant serum glycoprotein |
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Term
| Charcot Marie Tooth Disease |
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Definition
• Biochemistry
○ Mutations in Heat Shock Proteins genes leading to protein misfolding disorders
○ Heat schock proteins are chaperones that repair proteins damaged in the course of heat and other stresses. |
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Term
| Multiplesulfatase Deficiency |
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Definition
• Symptoms
○ Presents as mucopolysaccharidoses
• Biochemistry
○ Failure to convert cysteine to Calpha-formylglycine
○ Sulfated glycosaminoglycans accumulate in the lysosome |
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Term
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Definition
• Biochemistry
○ Caused by a deletion of just one codon from the CFT1 gene
○ Deletion interferes with folding and glycosylation of the protein. Instead of being routed to the plasma membrane, the CFTR protein is moved into the cytosol and degraded |
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Term
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Definition
• Biochemistry
○ Transfer of phosphate to mannose is impaired
○ Lysosomal proteins do not reach their compartment and lysosome function is impaired
○ Leads to accumulation of undegraded proteins in lysosomes
• Diagnosis
○ In fibroblasts, detect dense inclusion bodies consisting of nonfunctional lysosomes and their content
○ In serum, one can detect lysosomal proteins that did not reach their current destination |
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Term
| Deafness-dystonia syndrome |
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Definition
• Biochemistry
○ Rare mitochondrial disorder caused by a mutation in a TIM protein that impairs cellular energy production by preventing the assembly of fully functional mitochondria |
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Term
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Definition
• Symptoms
○ Vision problems, headaches, usually before 5 years of age
• Biochemistry
○ Malignancy in developing retina
○ Genetic (bilateral) -40%
○ Sporadic (unilateral) -60%
○ Rb1 is a tumor suppressor gene involved in regulation of cell cycle. Cyclin D-CDK4/6 (G1-CDk) and cyclin E-CDK2 (G1/S-Cdk) are the protein kinases that phosphorylate RB1.
○ Hypophosphorylated (unphosphorylated) RB1 binds transcription factor E2F and blocks transcription. Phosphorylation of RB1 causes dissociation of RB1 from E2F allowing transcription to procede
• Treatment
○ Chemotherapy with photocagulation (chemically designed to kill cancer cells, laser tretment to stop angiogenesis)
○ Drugs
○ Cryotherapy- frezing tumors
○ Plaque radiotherapy- small radioactive source in proximity to tumor
○ External beam radiotherapy |
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Term
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Definition
• Biochemistry
○ Translocation of chromosomes 8 and 14
○ Moves MYC from it's normal position on chromosome 8 to chromosome 14 next to immunoglobin heavy genes
○ Transcription of MYC is deregulated and under control of immunoglobulin heavy chain protomes
§ B cells whch continuously produce immunoglobulins, overproduce MYC proteins stimulating them to replicate |
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Term
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Definition
• Symptoms
○ Colorectal cancer
○ Not a large number of polys, but will progress to a carcinoma in only a few years
• Biochemistry
○ Inherited mutations in one of six genes that code for proteins required for mismatch repair
○ Microsatellite instability
§ Short tandem repeats found throughout genome prone to replication errors |
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Term
| FAP (Familial Adenomatous Polyposis Coli) |
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Definition
• Symptoms
○ Development of thousands of colon polyps as early as their teens
○ Polyps will slowly progress from adenomas to malignant carcinoma
• Biochemsitry
○ Mutation in the APC gene
§ Have one inherited mutant allele and mutation of other alleles will lead to invasive carcinoma
○ APC codes for tumor suppressor in Wnt cell-signaling pathway
§ Regulates Beta-catenin which is found bound to E-cadherin as well as free in cytosol
§ When Wnt binds to receptor, Beta-catenin will not be destroyed and will move to nucleus to activate transcription of growth promoting genes such as myc and cyclin D
○ No normal APC, then growth signaling will not take place |
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Term
| Chronic Myeloid Leukemia (CML) |
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Definition
• Symptoms
○ Cancer
• Biochemistry
○ Reciprocal translocation between chromosomes 9 and 22 resulting in the fusion of BCR and ABL
○ ABL encodes a tyrosine kinase that normally regulates apoptosis and several signaling pathways
§ BCR-ABL fusion protein is constitutively active and continually promotes cell division
• Treatment
○ Imatinib mesylate (Gleevec) is tyrosine kinase inhibitor that inhibits BCR-ABL |
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Term
| Non-small cell lung cancer |
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Definition
• Symptoms
○ Lung cancer
○ Increased by smoking
• Biochemistry
○ Mutations in the gene for the EGF receptor
• Treatment
○ Tyrosine kinase inhibitor gefitinib |
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Term
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Definition
| large intensely stained-has secondary structure, intense transcription of ribosomal RNA |
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Term
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Definition
| intense staining- DNA associated with proteins. transcriptionally silent |
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Term
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Definition
| transluscent staining- DNA not heavily associated with proteins-transcriptionally active |
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Term
| In what direction does DNA synthesis occur? |
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Definition
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Term
| What direction is the DNA polymerase delta proofreading activity in? |
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Definition
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Term
| How do repair enzymes work in error checking of newly synthesized DNA? |
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Definition
| Repair enzymes recognize distortion. Remove mismatched base. Excise nucleotides back to nearest nick. Fill in gap by DNA polymerase using parental DNA strand as template |
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Term
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Definition
Use: Treatment against cancer
Biochemistry: oligonucleotide that binds to the RNA template in the telomerase and inhibits telomerase enzymatic activity |
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Term
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Definition
Use: Treatment against HIV
Biochemistry: Re-activates telomerase in CD4 T-cells that have been disabled by HIV infection |
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Term
| What direction does RNA synthesis occur? |
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Definition
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Term
| What constitutes the transcription initiation complex? |
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Definition
| Binding of TFIID, RNA Pol II, and general transcription factors. Chromatin remodeling complex, histone-modifying enzymes |
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Term
| Which transcription factor unwinds the DNA helix? |
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Definition
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Term
| Three main steps of pre-mRNA processings. |
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Definition
Capping
Splicing
Polyadenylation |
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Term
| HATs (Histone acetyltransferases) |
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Definition
Acetylate certain lysine residues in the histones
Reduces the net positive charge on the histone protein which will weaken attraction between histone and negatively charged DNA molecule facilitating transcription. |
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Term
| HDACs (Histone Deacetylases) |
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Definition
| Molecules remove acetyl groups from th ehistones which increase net position charge and makes a stronger bond between histone and DNA. Inhibits transcription. |
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Term
| What effect does methylation have on transcription? |
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Definition
| Shutts down by binding proteins that have HDAC activity promoting DNA condensation |
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Term
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Definition
proto-oncogene
contains leucine zipper domain that allows it to dimerize with MAX
helix-turn-helix domain allowing it to bind to specific DNA sequences
elevated is seen in wide range of cancers |
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Term
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Definition
Integral membrane protein N-terminus is extracellular. Receptor recognizes apolipoprotein B and E of LDL and VDL
Binding of LDL or VDL to LDL receptor leads to endocytosis and uptake of LDL and VDL into cells.
Transcription of LDL receptor gene upregulated in response to low cellular cholesterol resulting in more LDL receptor production. |
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Term
| Sequence of LDL receptor gene transcription |
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Definition
GC boxes are recognized and bound by SP-1 (zinc-finger protein)
SP-1 requires CRSP-1 for activation
SRE-1 bound by SREPB-1a (leucine zipper protein)(maintained outside of nucleus when sufficient intracellular cholesterol is present)
SREBP-1a bound to SRE-1 recruits a HAT resulting in relaxation and LDL receptor gene transcription |
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Term
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Definition
Cross plasma membrane of cells and bind to soluble receptor present in cytoplasm or nucleus
DNA motifs are called HRE's (steroid Hormone Responsive Element)and are individually named for receptors they bind. |
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Term
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Definition
Secreted by adrenal cortex
Stimulates gluconeogenesis, glycogen depositioin, fat and protein degradation, inhibit inflammatoory response
Cortisol is major human one (regulates PEPCK gene) |
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Term
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Definition
T3 and T4 derived from tyrosine
Stimulate metabolic rate and bind to receptors present constitutively in nucleus
Receptors bound to DNA motifs of genes that respond to thyroid hormones (Ca 2+ transporting ATPase) |
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Term
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Definition
Estrogen enters cytoplasm and binds to estrogen receptor (dissociates from associated proteins)
Estrogen + receptor enters nucleus, dimerizes and binds to EREs. Initiate cofactors and transcription |
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Term
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Definition
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Term
| eukaryotic vs. prokaryotic mRNA |
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Definition
eukaryotic -monocistronic- one ORF per mRNA
prokaryotic -polycistronic - multile ORFs per mRNA |
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Term
| What is meant by the wobble position of tRNA? |
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Definition
| Final inosine base can pair with A, C, or U |
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Term
| How is amino acid linked to tRNA? |
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Definition
| tRNA + aminoacid + ATP -> aminoacyl-tRNA + ADP + P |
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Term
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Definition
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Term
| Regulation of translation |
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Definition
1. Recognition of start codon
2. Activity of initiation factors (phosphorylation of elF-2 inactivates it)
3. Use of internal ribosome entry sites (IRES)- 5' cap of mRNA mus interact with translation ractors to recognize start codon. |
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Term
| How do cells respond to massive amounts of unfolded protein? |
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Definition
Inhibit protein translation
Induce chaperone production
Consider apoptosis |
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Term
| What are glycosyltransferases specific for? |
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Definition
Sugar donor
Acceptor molecule
Type of glycosidic bond formed |
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Term
| Synthesis of N-linked Oligosaccharides |
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Definition
In ER: Synthesis of universal oligosaccharide on dolichol phosphate. Contains 14 sugars added by activated nucleotides
Transfer of universal oligosaccharide to nascent polypeptide chain
In Golgi: Highly specific modification of universal oligasaccharide by addition and removal of carbs. |
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Term
| Explain O-linked glycosylation |
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Definition
| Post-translational event on folded proteins in golgi apparatus. Glycosyltransferases transfer N-aceetyl-galactosamine to hydroxyl of serine or threonine residuses on surface. Then other sugars are added. |
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Term
| Three ways to modify aminoacid side chains of proteins. |
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Definition
hydroxylate protein for collagen
Acetylate lysine to change overall charge of DNA
convert thiol group of cysteine into aldehyde to form Calpha-formylglycine |
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Term
| Three ways to add hydrophobic moieties to proteins. |
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Definition
Addition of myristic acid to teh N-terminal amino acid (glycine)
Addition of palmitic acid to selected cysteine residues throughout the protein
Addition of isoprenoids to cysteine residues close to C-terminus |
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Term
| Steps of sending proteins to mitochondria |
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Definition
1. synthesized as large preproteins with an N-terminal presequence
2. Chaperones stabilize mito proteins in unfolded form
3. Presequences interact with receptor in outer mito membrane
4. TOM (translocase of outer membrane) and TIM (translocase of inner membrane) provide channel for preprotein to enter matrix.
5. presequence cleaved my mito proteases
6. proteins destined for inner and outer mito membrane contain signal sequence for insertion into membrane |
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Term
| Two mechanisms for protein degradation. |
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Definition
1. Lysosome to degrade extracellular proteins. Also functions in autophagy.
2. Proteasome required for deradation of cytoplasmic proteins |
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Term
| Lifespan of a protein determined by: |
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Definition
Conformation: Incorrect folded proteins are degraded quickly. Hydrophobic domain on surface is bad sign.
N-terminal residue: N-terminal arginines or lysines are less stable than N-terminal methionine or serine
Other elements: PEST sequence shortens life |
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Term
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Definition
| G1-Cdk (Cyclin D- Cdk 4, Cdk6) |
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Term
| What complex does p21 inhibit? |
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Definition
| G1/S-Cdk (Cyclin E - Cdk2) |
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Term
| What complex phosphorylates E2F? |
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Definition
| S-Cdk (Cyclin A- Cdk2, Cdk1) |
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Term
| What complex is inhibited by p27? |
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Definition
| S-Cdk (Cyclin A - Cdk2, Cdk1) |
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Term
| What are the effects of p-27 upregulation? |
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Definition
Inhibits all CDKs and is found at high levels in terminally differentiated cells
Induced by transforming growth factor Beta, cAMP, and contact inhibition |
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Term
| Passage from S through G2 |
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Definition
G2: Cyclin A complexed to Cdk-1 (S-Cdk)
After replication, M-Cdk starts to be formed
Spindle proteins and other materials for mitosis synthesized
S-Cdk phosphorylates origin of replication complex initiating replication |
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Term
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Definition
Anaphase: M-Cdk phosphorylates nuclear laminins and protein responsible for spindle apparatus
Chromosomes condense
APC (anaphase promoting complex) activated bringing separation |
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Term
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Definition
APC polyubiquinates S-Cdk and M-Cdk and anaphase inhibitory proteins
nuclear envelope forms
G1 cyclin-CDKs inactivate APC
Rb is dephosphorylated and cell enters g1 or exits into Go |
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Term
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Definition
G1/S: Restriction point-DNA damage delays progress
G2/M: DNA replicated? Environment suitable?
M-Anaphase: Chromosomes attached to spindles? |
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Term
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Definition
Activation of p53
External signals like TNF (tumor necrosis factor) or receptor Fas |
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Term
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Definition
Bcl-2 family of proteins
p-53 induces proapoptotic proteins
BH-3 only proteins activate Bax which forms channel in outer mito membrane
Cyto c escapes and binds to APAF-1 to form apoptosome that recruits and activates caspase 9
Caspase 9 activates executioner caspases 3, 6, and 7 |
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Term
| Two broad classes of genes that cause cancer |
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Definition
oncogenes- mutated forms of genes that stimulate cell division
tumor suppressor genes - genes that control cell division, DNA repair genes, apoptosis genes |
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Term
| Six abilities to become metastatic |
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Definition
Self-sufficiency in growth signals
Insensitivity to antigrowth signals
Evading apoptosis
Limitless Replicative Potential
Sustained angiogenesis
Tissue invasion and metastasis |
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Term
| Turning proto-oncogenes into oncogenes |
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Definition
Deletion or point mutation: hyperactive protein made in normal amounts
Regultory mutation: Normal protein greatly overproduced
Gene amplification: normal protein greatly overproduced
Chromosome rearrangement: nearby regulatory DNA sequence causes overproduction or fusion to actively transcribed gene produces hyperactive fusion protein |
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Term
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Definition
Erb B encodes epidermal growth factor receptor (tyrosine kinase) that lacks EGF binding site and is active in absence of EGF
uncontrolled activity passes on growth and proliferation signals in absence of growth factor signals. |
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