CELL BIOLOGY: BOARDS AND BEYOND Flashcards
What are telomeres?
Telomeres are nucleotide sequences located at the ends of chromosomes that protect them from deterioration or fusion with neighboring chromosomes.
What is the role of telomerase in cellular division?
Telomerase prevents the loss of telomeres, thus preventing the shortening of chromosomes with each cycle of DNA replication. It is especially important for rapidly dividing cells.
Why is telomerase particularly important for rapidly dividing cells?
Rapidly dividing cells are at risk of losing telomeres during cellular division, which can lead to chromosome shortening and potential genomic instability. Telomerase helps maintain telomere length in these cells.
How do cardiac myocytes relate to telomerase activity?
Cardiac myocytes are permanent cells that do not undergo cell division; therefore, they would not be affected by medications that inhibit telomerase.
What is polymyositis?
Polymyositis is an autoimmune inflammatory muscle disorder characterized by proximal muscle weakness, often affecting women aged 40 to 50 years
What are classic presenting symptoms of polymyositis?
Classic symptoms include proximal muscle weakness, difficulty climbing stairs, getting up from a chair, and carrying groceries.
What lab finding is commonly associated with polymyositis?
Serum creatinine kinase levels are increased due to muscle inflammation.
What is the most common antibody seen in polymyositis?
The most common antibody is anti-Jo1, which is directed against histidyl-tRNA synthetase.
What is the function of histidyl-tRNA synthetase?
Histidyl-tRNA synthetase catalyzes the transfer of histidine amino acids to the 3’ end of tRNA molecules during the process of tRNA charging.
What is diphtheria and what organism causes it?
Diphtheria is an infectious disease caused by the gram-positive bacillus Corynebacterium diphtheriae.
What are the common clinical features of diphtheria?
Clinical features include sore throat, malaise, low-grade fever, and cervical lymphadenopathy.
What classic examination finding is associated with diphtheria?
Examination of the pharynx typically shows a gray-white membrane composed of fibrin, inflammatory cells, bacteria, and necrotic debris.
Why is diphtheria rarely seen outside the developing world?
Diphtheria is rarely seen outside the developing world due to widespread vaccination against it.
What is the mechanism of action of diphtheria toxin?
Diphtheria toxin inactivates elongation factor 2 in human cells, which inhibits protein synthesis and leads to cell death.
What role do elongation factors play in protein synthesis?
Elongation factors facilitate the elongation phase of translation at ribosomes, allowing peptides to grow in length once translation has been initiated.
What aspects of protein synthesis are not directly affected by diphtheria toxin?
Charging of tRNA, initiation and termination of translation, and post-translational modification are not directly affected by diphtheria toxin.
What is the primary effect of diphtheria toxin on protein synthesis?
Diphtheria toxin primarily inhibits the activity of elongation factor 2, which arrests protein synthesis and leads to cell death.
What processes are involved in cellular protein synthesis?
Cellular protein synthesis involves:
- Charging of tRNA
- Initiation of translation
- Elongation of the polypeptide chain
- Termination of translation
- Post-translational modification
What is the most common cause of dilated cardiomyopathy?
Coronary artery disease, also known as ischemic cardiomyopathy.
Why is a coronary angiogram performed in patients with new-onset dilated cardiomyopathy?
A coronary angiogram is commonly performed to assess for ischemic causes of cardiomyopathy. A normal angiogram indicates a non-ischemic cause.
What is one of the non-ischemic causes of dilated cardiomyopathy associated with mitochondrial DNA?
A small number of cases of non-ischemic dilated cardiomyopathy are caused by mutations in mitochondrial DNA that code for tRNA molecules.
What is the significance of mutations in tRNA molecules related to dilated cardiomyopathy?
Mutations that alter the aminoacyl acceptor stem at the 3’ end of tRNA molecules can negatively affect protein synthesis, as this is where amino acids bind to tRNA.
How do modifications to tRNA affect protein synthesis?
Any negative modification to tRNA, including at the acceptor stem, decreases protein synthesis because tRNA is responsible for transporting amino acids to growing protein chains.
What does “terminally differentiated” mean in the context of cardiac myocytes?
“Terminally differentiated” means that cardiac myocytes do not divide and cannot regenerate after cell death, such as in a myocardial infarction.
How do cardiac myocytes respond to stressors like hypertension?
Cardiac myocytes develop hypertrophy (increase in cell size) but do not undergo hyperplasia (increase in cell number) when exposed to stressors like hypertension.
How do mutations in mitochondrial DNA affect oxidative phosphorylation?
Mutations in mitochondrial DNA decrease, rather than increase, the process of oxidative phosphorylation.
Would a change in cellular tRNA affect mitochondrial function?
No, a change in cellular tRNA would not affect the mitochondria directly, as tRNA operates in the cytoplasm for protein synthesis.
What is the function of aminoacyl-tRNA synthetases?
Aminoacyl-tRNA synthetases are enzymes that attach the appropriate amino acids to the 3’ end of tRNA molecules as part of protein translation.
How many different aminoacyl-tRNA synthetases are there in the human body?
There are 20 different aminoacyl-tRNA synthetases in the human body, one for each amino acid of the genetic code.
What additional function do aminoacyl-tRNA synthetases perform besides attaching amino acids to tRNA?
Aminoacyl-tRNA synthetases perform hydrolytic editing, which involves scrutinizing amino acid attachments to ensure the correct amino acid is present on the tRNA.
What does it mean if a tRNA molecule has an incorrect amino acid attached?
This condition, known as a “mischarged” tRNA, indicates an error in the function of aminoacyl-tRNA synthetase.
What are the three stages of protein translation?
The three stages of protein translation are initiation, elongation, and termination.
What role does peptidyl transferase play in protein synthesis?
Peptidyl transferase, which is part of the ribosome, catalyzes the transfer of amino acids bound to tRNA to the growing peptide chain.
What would be the consequence of a failure in the peptidyl transferase enzyme?
Failure of peptidyl transferase would result in a failure of protein synthesis but would not cause mischarging of tRNA molecules.
What is the role of RNA polymerase III in protein synthesis?
RNA polymerase III synthesizes tRNA molecules.
What does it indicate if there is an abnormal tRNA molecule despite a normal genetic code?
An abnormal tRNA molecule despite a normal genetic code indicates an error in tRNA synthesis by RNA polymerase III.
What happens when there are functional errors in aminoacyl-tRNA synthetases?
Functional errors in aminoacyl-tRNA synthetases lead to mischarged tRNA molecules, where the attached amino acid does not match the genetic code of the tRNA anticodon.
What is the function of aminoacyl-tRNA synthetases?
Aminoacyl-tRNA synthetases are enzymes that attach the appropriate amino acids to the 3’ end of tRNA molecules during protein translation.
What process does mRNA undergo before it exits the nucleus?
mRNA undergoes splicing, which removes introns from the transcript.
What are the signals that identify introns during splicing?
Introns are identified by a GU at the 5’ end and an AG at the 3’ end.
What happens to the mRNA sequence after splicing?
After splicing, the mRNA sequence will be similar to the original DNA sequence, with the bases between GU and AG (the introns) removed.
What is the significance of splicing in eukaryotic gene expression?
Splicing is crucial for producing a mature mRNA transcript that can be translated into a functional protein, allowing for proper gene expression.
What are the presenting symptoms of acute liver injury in this case?
The woman presents with jaundice, altered mental status, and marked elevations in serum aminotransferases.
What is the significance of marked elevations in aminotransferases (>1000)?
Marked elevations in aminotransferases indicate acute liver injury and have a limited differential diagnosis, including acute viral hepatitis, acute alcoholic hepatitis, acetaminophen toxicity, shock liver, and toxin exposure
What mushroom is associated with severe liver toxicity?
The death cap mushroom (Amanita phalloides) is associated with severe liver toxicity.
What toxin does the death cap mushroom produce, and what is its effect?
The death cap mushroom produces alpha amanitin, which inhibits RNA polymerase II in liver cells, preventing hepatocytes from synthesizing mRNA from DNA.
What are potential complications of Amanita phalloides poisoning?
Complications can include life-threatening hepatic failure, hypoglycemia, coagulopathy (evidenced by increased INR), and multi-organ failure.
What does an increased INR indicate in the context of liver injury?
An increased INR indicates coagulopathy, which can result from liver dysfunction due to acute liver injury.
What are the key symptoms of pulmonary tuberculosis (TB) in this patient?
The patient presents with night sweats, weight loss, hemoptysis, and the presence of acid-fast organisms in his sputum.
What is the standard treatment regimen for tuberculosis?
The standard treatment regimen for TB includes a combination of rifampin, isoniazid, pyrazinamide, and ethambutol.
What unique side effect is associated with rifampin?
Rifampin is known for causing orange-red discoloration of tears, saliva, urine, and feces due to its metabolites.
Is the orange-red discoloration caused by rifampin harmful?
No, the orange-red discoloration is a benign change that patients often notice and report to healthcare providers.
What is the mechanism of action of rifampin?
Rifampin works by inhibiting bacterial RNA polymerase, which is essential for RNA synthesis in bacteria.
What is the mechanism of action of beta-lactam antibiotics?
Beta-lactam antibiotics prevent cross-linking of peptidoglycan in bacterial cell walls.
What is the mechanism of action of macrolide antibiotics?
Macrolide antibiotics inhibit bacterial protein synthesis by preventing ribosome translocation.
Inhibits the synthesis of mycolic acids, a key component of mycobacterial cell walls.
Isoniazid
What is a key characteristic that distinguishes enhancer DNA regions from promoters?
Enhancers bind transcription factors and increase gene transcription, while promoters are located directly upstream of a gene.
Where can enhancers be located in relation to the gene they regulate?
Enhancers can be found many nucleotides up or downstream of the gene they act upon due to DNA coiling.
What role do enhancers play in gene transcription?
Enhancers increase gene transcription by binding transcription factors.
hat do both enhancers and promoters have in common regarding transcription factors?
Both enhancers and promoters bind to transcription factors.
Where are promoters typically located in relation to the gene they regulate?
Promoters are found upstream of the gene they act upon.
Can enhancers be located only upstream of the gene they regulate?
No, enhancers can be found both upstream and downstream of the gene they act upon.
What is the TATA box?
The TATA box, with the sequence TATAAA, is a classic promoter region.
What identifies RNA fragments as mRNA?
The presence of a 5’ 7-methylguanosine cap identifies RNA fragments as mRNA.
What are the types of mRNA found in the nucleus?
Multiple types of mRNA found in the nucleus include pre-mRNA (which contains introns) and mature mRNA.
What types of RNA are closely associated with ribosomes during translation?
Messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA) are all found associated with ribosomes during translation.
Where is messenger RNA moved to in the cytoplasm?
Messenger RNA is moved to processing bodies in the cytoplasm.
What other types of RNA can be found in processing bodies besides mRNA?
micro RNA (miRNA).
What are introns, and where are they found?
Introns are nucleotide sequences that are removed by RNA splicing and are found within mRNA and also tRNA.
What are the key findings consistent with aplastic anemia in this boy?
The boy has anemia, thrombocytopenia, and neutropenia.
What physical features suggest a diagnosis of Fanconi anemia?
Short stature and abnormal thumbs suggest a diagnosis of Fanconi anemia.
What causes Fanconi anemia?
mutations in DNA repair genes.
What is the major role of Fanconi anemia genes?
The major role of Fanconi anemia genes is to repair DNA interstrand crosslinks.
How are DNA interstrand crosslinks typically repaired in normal cells?
In normal cells, lesions are removed by enzymes that create a double-strand DNA break at the site of the crosslink, and then the break is repaired.
What happens to children with Fanconi anemia regarding DNA repair?
Children with Fanconi anemia have impaired repair of DNA interstrand crosslinks, leading to accumulation of crosslinks and failure of double-strand repair mechanisms.
What is the mechanism by which pyrimidine dimers are removed from DNA?
Through nucleotide excision repair.
What condition is caused by defects in nucleotide excision repair?
Xeroderma pigmentosa
What is the function of mismatch repair during DNA synthesis?
Mismatch repair resolves incorrectly paired bases or nucleotides during DNA synthesis.
What can failure of mismatch repair lead to?
Failure of mismatch repair can lead to microsatellite instability and Hereditary Non-Polyposis Colorectal Cancer (HNPCC)
Is a substance used widely as a solvent for industrial manufacturing processes (e.g., rubber manufacturing). Exposure can lead to aplastic anemia. This child has poor growth and abnormal thumbs, suggesting a genetic cause rather than an environmental cause of his condition.
Benzene
What does a variable number of repeating DNA segments among cells indicate in this man with colon cancer?
This is termed microsatellite instability, which is due to a failure in DNA mismatch repair.
When does DNA mismatch repair occur in the cell cycle?
DNA mismatch repair takes place during the S/G2 phase of the cell cycle when DNA replication is occurring.
What are the two mechanisms that repair DNA double-strand breaks?
DNA double-strand breaks are repaired by homologous recombination and non-homologous end joining.
What conditions may result from the failure of DNA double-strand break repair mechanisms?
Failure of these mechanisms may lead to Fanconi anemia or ataxia telangiectasia.
What are the typical clinical features of ataxia telangiectasia (AT)?
Being confined to a wheelchair, recurrent upper respiratory infections, and telangiectasias on the skin.
What genetic mutation causes ataxia telangiectasia?
Mutation in the ATM gene.
How does the mutation in the ATM gene affect DNA repair?
The mutation prevents the repair of double-stranded DNA breaks through non-homologous end joining.
What is the consequence of the DNA repair defect in children with ataxia telangiectasia?
Affected children are at increased risk for DNA damage from ionizing radiation, which can lead to cancer.
What is the cause of sensitivity to UV radiation in xeroderma pigmentosum?
Sensitivity to UV radiation in xeroderma pigmentosum is due to defective nucleotide excision repair.
When do affected children typically start showing sensitivity to sunlight in xeroderma pigmentosum?
Affected children are sensitive to sunlight starting in infancy and typically have numerous freckles on their skin.
What type of radiation are patients with ataxia telangiectasia sensitive to?
Ionizing radiation, not UV radiation.
What defines ionizing radiation?
Ionizing radiation is radiation with enough energy to knock electrons from molecules, causing ionization. UV radiation is non-ionizing and comes largely from the sun, while ionizing radiation has enough energy to cause ionization.
What initiates the base excision repair process?
Base excision repair begins when DNA glycosylase removes damaged nitrogenous bases, leaving a “baseless” nucleotide.
What is the role of AP endonuclease in base excision repair?
AP endonuclease breaks the bond at the 5’ end of the baseless nucleotide.
What does AP lyase do during base excision repair?
AP lyase breaks the bond at the 3’ end of the baseless nucleotide, removing the entire damaged nucleotide.
Which enzymes fill in the gap after a damaged nucleotide is removed in base excision repair?
DNA polymerase and ligase fill in the gap.
What does the presence of a bond remaining at the 3’ end of a baseless nucleotide indicate?
It indicates a lack of AP lyase function, whose normal role is to break the 3’ bond.
This child with extreme sun sensitivity, freckles, and dry skin has xeroderma pigmentosum, a disease caused by defective nucleotide excision repair. This repair mechanism is responsible for
Removing pyrimidine dimers caused by UV light exposure.
What is a silent mutation?
Is a nucleotide change that does not alter the final protein product of a gene.
Why do point mutations that occur in the third position of a codon often result in silent mutations?
Point mutations at position 3 of a codon are often silent because codons that differ at this position can generate the same amino acid, as described by the “Wobble” hypothesis.
Point mutations involving a start codon are
Never silent
UAA
A stop codon
In the context of Duchenne muscular dystrophy (DMD), how can a parent carry a germline mutation yet test negative using standard techniques?
The parent will test negative for the mutation because standard techniques often sample DNA from somatic cells (like the oral mucosa), where the mutation is not present.
What are two genetic disorders associated with germline mutations?
Osteogenesis imperfecta (OI) and Duchenne muscular dystrophy (DMD)
How can a child inherit a genetic disorder from parents who do not show the disease gene?
A child can inherit the disorder due to a new (sporadic, spontaneous, or de novo) mutation, which may not be present in the parents’ somatic cells.
When is a germline mutation revealed in families where the parents do not initially test positive?
The germline mutation is revealed when additional children are born with the same mutation, indicating it originated from one of the parents.
What is a nonsense mutation?
A nonsense mutation is a DNA point mutation that results in an early stop codon, leading to a shortened amino acid sequence.
What are the three RNA stop codons?
UAG
UGA
UAA
What are the corresponding coding strand DNA sequences for the RNA stop codons?
The corresponding coding strand DNA sequences are:
UAG → TAG
UGA → TGA
UAA → TAA
What must a point mutation result in to cause a nonsense mutation?
A point mutation must result in one of the stop codon sequences (TAG, TGA, or TAA) to cause a nonsense mutation.
What are common symptoms of sickle cell anemia?
Common symptoms include hemolytic anemia, dyspnea, and recurrent pain crises that may resolve with fluid and blood transfusions.
What genetic mutation causes sickle cell anemia?
Sickle cell anemia is caused by a missense mutation in the beta globin gene.
What is a missense mutation?
A missense mutation is a genetic alteration that substitutes one amino acid for another in a protein.
What amino acid substitution occurs in sickle cell anemia?
In sickle cell anemia, valine is substituted for glutamate in the beta chains of hemoglobin.
What effect does the sickle cell mutation have on hemoglobin?
The mutation causes hemoglobin to denature and precipitate in the deoxygenated state, leading to the sickling of red blood cells.
What are the consequences of sickled red blood cells in the body?
Sickled red blood cells can damage cell membranes, leading to hemolytic anemia, tissue ischemia, and pain due to blockage in small caliber vessels.
Are caused by insertions or deletions of nucleotides in multiples not divisible by three. Because of the genetic code which places amino acids based on three-nucleotide DNA sequences, a frameshift mutation “shifts the reading frame”, resulting in completely different protein products of translation.
Frameshift mutations
What genetic mutation causes cystic fibrosis (CF)?
Cystic fibrosis is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene on chromosome 7.
