Biochemistry Flashcards
(135 cards)
1
Q
What is the role of DNA methylation?
A
DNA methylation reversibly alters gene expression without changing the DNA sequence. It plays a key role in:
Gene silencing
Genomic imprinting
X chromosome inactivation (lyonization)
Aging, carcinogenesis, and epigenetics
Transposable element repression
2
Q
What is the link between DNA methylation and CpG islands?
A
DNA methylation often occurs at CpG islands in gene promoter regions, leading to transcriptional repression.
🔹 “CpG methylation makes DNA mute.”
3
Q
What diseases are associated with dysregulated DNA methylation?
A
Fragile X syndrome (hypermethylation of the FMR1 gene)
Cancers involving abnormal methylation of tumor suppressor genes, such as: Colorectal cancer,
Breast cancer (e.g., BRCA1 promoter methylation), Lung cancer, Glioblastoma, Leukemia
4
Q
In which cancers is homologous recombination impaired?
A
Breast and ovarian cancers from BRCA1 and BRCA2 mutations.
5
Q
Which disorder has a defective nucleotide excision repair?
A
Xeroderma pigmentosum: a rare autosomal recessive disorder caused by a defect in nucleotide excision repair (NER) — the DNA repair mechanism that normally fixes damage from ultraviolet (UV) light, particularly thymine dimers.
6
Q
What disorder results from defective mismatch repair, and what are its clinical consequences?
A
Lynch syndrome (Hereditary Nonpolyposis Colorectal Cancer) arises from mutations in mismatch repair genes (e.g., MLH1, MSH2). This leads to microsatellite instability and greatly increases the risk of colorectal, endometrial, and other cancers, often at a young age and without many polyps.
7
Q
What type of mutation causes sickle cell disease?
A
Missense mutation substituting glutamic acid with valine
8
Q
What type of mutation is involved in Duchenne muscular dystrophy, what is it, and what other diseases does it cause?
A
Frameshift mutation: deletion or insertion of any number of nucleotide non-dividable by 3, disrupting the reading of all downstream codons.
DMD
Tay-sachs disease
Cystic fibrosis
9
Q
What are the start and stop codons?
A
10
Q
What are cyclin-CDK complexes and what is their role in the cell cycle?
A
Cyclin-CDK complexes are phase-specific protein complexes that form when cyclins activate cyclin-dependent kinases (CDKs). Once formed, the complex phosphorylates other proteins (e.g., Rb) to regulate progression through the cell cycle.
These complexes must be precisely activated or inactivated at key checkpoints to ensure normal cell division.
11
Q
Is Rb a cell cycle progressor or suppressor?
A
Rb (retinoblastoma protein) is a tumor suppressor that inhibits cell cycle progression from G₁ to S phase . When phosphorylated by Cyclin-CDK, Rb is inactivated, allowing the cell cycle to proceed.
12
Q
How do growth factors affect the cell cycle?
A
Growth factors (e.g., EGF, insulin) bind to tyrosine kinase receptors, activating signaling pathways that increase cyclin expression. This promotes Cyclin-CDK complex formation, leading to Rb phosphorylation and progression from G₁ to S phase.
13
Q
What is the difference between permanent, stable and labile cells? Explain in terms of cell cycle phases and name the cells in each category.
A
14
Q
How does p53 promote apoptosis?
A
In response to DNA damage, p53 suppresses BCL-2 and BCL-XL and activates BAX/BAK, triggering the intrinsic apoptotic pathway via caspase activation. This eliminates damaged cells and prevents tumor formation.
15
Q
What is Li-Fraumeni syndrome and what gene is involved?
A
Li-Fraumeni syndrome is an inherited cancer predisposition syndrome caused by germline mutations in the TP53 gene, leading to loss of p53 function. It results in early-onset, multiple cancers including sarcomas, breast cancer, leukemia, brain tumors, and adrenal carcinomas.
16
Q
Hepatocytes and steroid-producing cells in the adrenal cortex are rich in [which organelle]?
A
17
Q
Mucous-secreting Goblet cells in the small intestine and antibody-secreting plasma cells are rich in [which organelle]?
A
Rough endoplasmic reticulum
18
Q
Which protein does colchicine (anti-gout) act on?
A
Microtubules
19
Q
Which syndrome most commonly has primary ciliary dyskinesia?
A
Kartagener syndrome: PCD + situs invertus
20
Q
Manifestations of primary ciliary dyskinesia
A
21
Q
What is a diagnostic clue for primary ciliary dyskinesia (PCD)?
A
Markedly decreased nasal nitric oxide (nNO) is a key diagnostic clue for PCD. Although not the cause, low nNO reflects defective ciliary signaling and is used as a non-invasive screening tool.
22
Q
How does the Na⁺/K⁺ ATPase work and what is its role?
A
The Na⁺/K⁺ ATPase uses 1 ATP to pump 3 Na⁺ out and 2 K⁺ in, maintaining ion gradients and a negative resting membrane potential.
23
Q
How does digoxin work and what is its effect? When is it used?
A
Digoxin is a cardiac glycoside that inhibits the Na⁺/K⁺ ATPase pump in cardiac myocytes. It is used to increase cardiac contractility in patients with heart failure and for rate control in AFib.
24
Q
What are the major types of collagen and where are they found?
A
25
What causes osteogenesis imperfecta, how is it inherited, and what are its major features (4)?
Osteogenesis imperfecta is usually autosomal dominant and caused by mutations in COL1A1/COL1A2, leading to **decreased production of otherwise normal type I collagen**. It presents with **frequent fractures, blue sclerae, dentinogenesis imperfecta, and hearing loss**.
26
What is Ehlers-Danlos syndrome and what are its major features?
Ehlers-Danlos syndrome is a group of inherited connective tissue disorders caused by defective collagen synthesis. It presents with hyperextensible skin, joint hypermobility, easy bruising, and fragile tissues. The vascular type (type IV) involves type III collagen and carries a risk of arterial or organ rupture.
27
How do the clinical manifestations of Marfan syndrome and Ehlers-Danlos syndrome differ?
Marfan: Tall stature, long limbs, aortic root dilation, lens dislocation, due to fibrillin-1 defect.
Ehlers-Danlos: Hyperextensible skin, joint hypermobility, poor wound healing, vascular rupture (in type IV), due to collagen defects.
28
Compare and contrast Marfan's from homocysteinuria
29
What are the steps of PCR and their purpose?
1. Denaturation (~95°C): Heat separates DNA strands
2. Annealing (~50–65°C): Primers bind to target sequence
3. Elongation (~72°C): DNA polymerase adds dNTPs to build new strands
30
What is the genetic defect in Li-Fraumeni syndrome?
An inactivating germline mutation in one allele of the TP53 tumor suppressor gene. A second somatic mutation (“second hit”) inactivates the other allele, leading to cancer (two-hit hypothesis).
31
What type of protein regulates embryonic cell differentiation and can induce dedifferentiation?
Transcription factors regulate embryonic differentiation by controlling gene expression specific to each cell type. They can also induce dedifferentiation, reverting mature cells (e.g., fibroblasts) to a pluripotent stem cell state by altering the transcriptional program.
32
What is the likely consequence of cytosine methylation at CpG sites in malignant DNA?
Gene silencing. Methylation of CpG islands (especially in promoter regions) suppresses gene transcription, a common mechanism in cancer.
33
What is CRISPR/Cas9?
CRISPR/Cas9 is a powerful genome editing tool derived from a natural defense mechanism used by bacteria. It enables scientists to precisely alter DNA sequences in living cells.
34
What is CRISPR/Cas9 used for?
35
What is the difference between Northern, Southern and Western blots?
Northern: RNA
Southern: DNA
Western: protein
36
What is codominance?
Codominance occurs when both alleles contribute to the phenotype of a heterozygote.
Example: Blood groups A, B, AB; α₁-antitrypsin deficiency; HLA types.
37
What is pleiotropy?
Pleiotropy is when one gene influences multiple phenotypic traits.
Example: Cystic fibrosis affects lungs, GI tract, pancreas, and male fertility.
38
What is anticipation?
Anticipation is when a genetic disorder appears with increased severity or earlier onset in successive generations.
Example: Trinucleotide repeat disorders (e.g., Huntington disease).
39
What is epistasis?
Epistasis occurs when an allele of one gene affects the expression of alleles at a different gene.
Example: Albinism or alopecia masking other traits.
40
What is variable expressivity?
Variable expressivity means that individuals with the same genotype show different phenotypes or severity.
Example: Neurofibromatosis type 1 shows varying symptoms between patients.
41
What are the most common trinucleotide repeat disorders, their mode of inheritance, their genes and their main manifestations?
42
What is genomic imprinting?
Genomic imprinting is when one parent's allele is silenced by methylation, and only the other parent’s copy is expressed. The expressed copy may be mutated, silenced, or deleted, causing disease.
43
What causes Prader-Willi syndrome?
Prader-Willi syndrome occurs when the paternal allele on chromosome 15 is deleted or mutated, or due to maternal uniparental disomy.
Normally, the mother's allele is silenced, so defect in the father's = disease
44
What are the signs and symptoms of Prader-Willi syndrome in infancy vs childhood?
45
What causes Angelman syndrome?
Angelman syndrome occurs when the maternal allele (UBE3A) is deleted or mutated, or due to imprinting errors or paternal uniparental disomy.
Normally, the paternal allele is silenced, so defect in the mother's = disease
46
What are the signs and symptoms of Angelman syndrome?
Hand-flapping, ataxia, severe intellectual disability, inappropriate laughter, seizures. (Mnemonic: HAILS the Angels)
47
What chromosome is involved in both Prader-Willi and Angelman syndromes?
Both syndromes involve chromosome 15.
48
What is the normal imprinting pattern on chromosome 15 for Prader-Willi and Angelman syndromes?
Normally, on chromosome 15, maternally derived genes are silenced (except for UBE3A), and paternally derived genes are expressed.
49
What is the inheritance pattern of mitochondrial diseases?
Mitochondrial diseases are transmitted only through the mother because mitochondria (and mtDNA) are inherited maternally. All offspring of an affected female may show signs of disease, but expression can vary due to heteroplasmy.
50
What is heteroplasmy?
Heteroplasmy is the presence of both normal and mutated mitochondrial DNA (mtDNA), resulting in variable expression in mitochondrially inherited diseases. mtDNA is passed from mother to all children.
51
What is a common cause of death in DMD
Dilated cardiomyopathy
52
Pathogenesis of DMD
53
Specific sign for DMD
Gower's sign
54
Which tissues are most affected by mitochondrial diseases?
Those with the highest O2 demand (CNS, skeletal muscle)
55
What is the most common INHERITED cause of intellectual disability?
Fragile X syndrome
56
What is the most common SPORADIC cause of intellectual disability?
Down syndrome
57
Pathogenesis of Fragile X syndrome
Trinucleotide repeat expansion (CGG)
Hypermethylation of cytosine residues = decreased expression
58
Pre-mutation vs full mutation of Fragile X syndrome
59
3 commonest trisomies in order of commonness
Down (21) > Edwards (18) > Patau (13)
60
Findings of first trimester ultrasound for Trisomy 21
**Ultrasound**
Increased nuchal translucency
Hypoplastic nasal bone
**Markers**
Increased hCG
Increased inhibin
61
Death by which age for T13 and T18?
By age 1.
62
What is PAPP-A and what might low levels of this protein indicate?
PAPP-A (Pregnancy-Associated Plasma Protein A) is a protein produced by the placenta during pregnancy. Low levels in the first trimester are associated with chromosomal abnormalities such as Trisomy 21 (Down syndrome), Trisomy 18, and Trisomy 13.
63
What is AFP?
AFP (Alpha-Fetoprotein) is a protein produced by the fetal liver. In second-trimester screening, low levels may indicate Trisomy 21 or Trisomy 18, while high levels can be associated with neural tube defects like spina bifida.
64
Comorbidities associated with Patau syndrome
Trisomy 13
Midline defects (defects in fusion of the prechordal mesoderm)
Cleft lip/palate
Holoprosencephaly
Polydactly
Cutis aplasia (absence of a portion of skin, most commonly on the scalp)
CHD
Polycystic kidney disease
65
Chromosome for Cystic Fibrosis
Chr 7
66
Chromosome for Marfan's
Chr 15
67
3 parts of the GI tract that must be intact for proper fat-soluble vitamin digestion
Pancreas
Biliary tract
Ileum
68
Is toxicity more common for fat-soluble or water-soluble vitamins?
Fat, because they can accumulate in fat
69
2 diseases that may cause fat-soluble vitamin malabsorption
CF
Celiac
70
What are the three types of Vitamin A?
Retinal
Retinol
Retinoic acid
71
What is the normal function of Vitamin A?
Antioxidant
Constituent of visual pigments (Retinal)
Essential for normal differentiation of **epithelial cells** into specialized tissue
72
What kind of metaplasia does Vitamin A normally inhibit?
Squamous metaplasia
73
What types of Vitamin A derivatives are used pharmacologically and for what are they prescribed?
Acute promyelocytic. leukemia: **all-trans retinoid acid**
Cystic acne: isotretinoin
74
Symptoms of Vitamin A deficiency
Night blindness
Dry scaly skin
Dry eyes
Immunosuppression
Corneal degeneration
**Squamous metaplasia of the conjunctiva**: Bitot spots
75
Acute vs chronic Vitamin A toxicity
76
Other name for Vitamin B1
Thiamine
77
What is the pathogenesis of Vitamin B1 (thiamine) deficiency?
Vitamin B1 deficiency impairs glucose breakdown, leading to decreased ATP production. This primarily affects highly aerobic tissues such as the brain and heart.
ATP depletion is worsened by glucose infusion, which **increases the metabolic demand without sufficient thiamine** to support energy generation.
78
How should patients with suspected Vitamin B1 (thiamine) deficiency be managed?
In patients with chronic alcohol use or malnutrition, always administer thiamine before giving dextrose to reduce the risk of precipitating Wernicke encephalopathy. Thiamine is essential for glucose metabolism; giving glucose first can worsen ATP depletion in thiamine-deficient tissues, especially the brain.
79
Risk factors for Vitamin B1 deficiency
Chronic alcohol use
Malnutrition
80
What syndromes are associated with Vitamin B1 deficiency?
81
Difference between Wernicke, Korsakoff, and Wenicke-Korsakoff syndromes
All: vitamin B1 deficiency
82
Which vitamin are NAD+ and NADP+ derived from?
Vitamin B3
83
What is pellagra?
84
Other name for Vitamin B9
Folate
85
In which foods is folate normally found and where is it absorbed in the GI tract?
In leafy vegetables
Absorbed in the jejunum
86
Symptoms of Vitamin B9 deficiency
Folate deficiency
87
Difference in neurological symptoms between B9 vs B12 deficiencies
B9 = no neuro deficiencies
B12 = paresthesias and subacute combined degeneration
88
Other name for Vitamin B12
Cobalamin
89
In which foods is cobalamin normally found?
Animal products
90
How much time is B12 stored in the body, and where?
Liver for 3-4 years
So symptoms of B12 deficiency would appear very late
91
Symptoms of B12 deficiency
Macrocytic megaloblastic anemia
Hypersegmented neutrophils
Subacute combined degeneration (degeneration of dorsal columns, lateral corticospinal tracts and spinocerebellar tracts)
Paresthesias
92
What happens in dual B9 and B12 deficiency only treated with B9 supplements
93
Other name for Vitamin C
Ascorbic acid
94
What is the function of Vitamin C (ascorbic acid)?
Vitamin C is an antioxidant that facilitates iron absorption by reducing Fe³⁺ to Fe²⁺. It's essential for collagen synthesis (via proline and lysine hydroxylation) and for converting dopamine to norepinephrine.
95
What are the signs and symptoms of Vitamin C deficiency?
Scurvy presents with swollen gums, easy bruising, petechiae, hemarthrosis, anemia, poor wound healing, perifollicular hemorrhages, and “corkscrew” hairs. It results from impaired collagen synthesis and weakens the immune response.
96
What kind of diet can precipitate Vitamin C deficiency?
A "tea and toast" diet, which is low in fruits and vegetables, can precipitate Vitamin C deficiency by lacking adequate ascorbic acid intake.
97
What are the effects of Vitamin C excess?
Excess Vitamin C can cause nausea, vomiting, diarrhea, fatigue, and calcium oxalate kidney stones. It may also worsen iron overload disorders like hemochromatosis by increasing iron absorption.
98
What are the sources of Vitamin D?
99
What is the primary function of Vitamin D?
Vitamin D increases intestinal absorption of calcium (Ca²⁺) and phosphate (PO₄³⁻) from the kidneys, bones and intestine.
100
What regulates Vitamin D production?
101
What are the clinical features of Vitamin D deficiency?
102
What are the causes of Vitamin D deficiency?
103
Which clotting factors are Vitamin K–dependent?
Vitamin K is necessary for the maturation of clotting factors II, VII, IX, and X, as well as proteins C and S, which are involved in the regulation of coagulation.
104
How does Warfarin act as an anticoagulant?
Warfarin inhibits vitamin K epoxide reductase, blocking the recycling of vitamin K to its active form. This prevents the γ-carboxylation of clotting factors II, VII, IX, X and proteins C and S, thereby impairing clot formation.
105
How does Vitamin K deficiency present in the newborn and what are the markers?
106
What causes Kwashiorkor?
Protein malnutrition
107
What causes Phenylketonuria (PKU) and when is the syndrome detected?
It arises due to **autosomal recessive genetic mutations**, leading to Phenylketonuria (PKU) (because of deficiency of phenylalanine hydroxylase or its cofactor BH₄)
Symptoms typically appear after birth, once maternal enzymes are no longer available, which is why **newborn screening is done 2–3 days after birth**.
108
What is the function of primase in prokaryotic DNA replication?
Primase is an RNA polymerase that synthesizes a short RNA primer on the DNA template. This primer provides a 3' hydroxyl group for DNA polymerase to initiate DNA synthesis, as DNA polymerase cannot start synthesis de novo.
109
What is the function of DNA ligase?
DNA ligase is responsible for repairing single-strand breaks in duplex DNA. It joins Okazaki fragments on the lagging strand and also functions in DNA repair.
110
What is the function of DNA polymerase III in prokaryotic replication?
DNA polymerase III is the main enzyme for synthesizing the daughter DNA strands.
It also has **3'→5' exonuclease activity that allows proofreading** to correct mismatched nucleotides during replication.
111
What is the function of DNA polymerase I in prokaryotic replication?
DNA polymerase I removes RNA primers and replaces them with DNA. It has 5'→3' exonuclease activity to remove RNA primers and 3'→5' exonuclease activity for proofreading.
112
How do the exonuclease activities of DNA polymerase I and DNA polymerase III differ in prokaryotic DNA replication?
113
How do you approach a genetic problem when one parent's carrier status is unknown (e.g., autosomal recessive diseases like cystic fibrosis)?
Use family history to determine the probability that the parent is a carrier.
If a parent is unaffected but has an affected sibling, their chance of being a carrier is 2/3 (excluding the 1/4 homozygous affected and 1/4 homozygous normal).
Multiply the probability of being a carrier by the chance of passing on the allele (½).
Example: 2/3 chance of being a carrier × ½ chance of passing the allele = 1/3 chance of passing it on.
If the other parent is known to be affected (100% chance of passing the allele), multiply accordingly to find the child’s chance of being affected.
In this case: 1/3 × 1 = 1/3 (33%)
114
Clues on history for PKU
Eczematous rash
Musty body odor
Intellectual disability
Gait abnormalities
115
What is the wobble hypothesis in the genetic code?
the third base of a codon can form non-standard base pairs with the anticodon of tRNA, allowing one tRNA to recognize multiple codons for the same amino acid. This increases efficiency and reduces the number of tRNAs needed
116
How can cancer cells use alternative splicing to evade apoptosis?
Cancer cells may use alternative splicing to remove the exon encoding the transmembrane domain of the Fas receptor (FasR), producing a soluble form that is not expressed on the cell surface. This prevents Fas-FasL interaction and allows the cells to evade apoptosis.
117
When to suspect achondroplasia?
118
What are telomeres and why are they important?
Telomeres are repetitive DNA sequences (e.g., TTAGGG) and associated proteins at the ends of chromosomes. They prevent chromosomal degradation and fusion, preserving chromosomal integrity during cell division.
119
What types of cells are most affected by defective telomeres?
Cells with a high turnover rate—such as epithelial cells, lymphocytes, and hematopoietic stem cells—are most affected because they divide frequently and depend on telomere maintenance for genomic stability.
120
How does dyskeratosis congenita typically present?
121
What is the inheritance pattern of Hemophilia A and B?
X-linked recessive pattern
122
How do you calculate the probability of an affected child in an X-linked recessive condition when the mother’s carrier status and the baby’s sex are unknown?
123
Why do stem cells have very long telomeres?
Stem cells have long telomeres due to high telomerase activity, which allows them to proliferate indefinitely while maintaining chromosomal integrity. In contrast, most differentiated adult cells lack telomerase, so their telomeres shorten with each division, leading to cell aging or death.
124
What are the two main types of stem cells, and what are their roles?
125
What type of protein is most likely detected when double-stranded DNA probes are used after gel electrophoresis and transfer to a membrane?
Transcription factors, because they bind specific DNA sequences and can be detected using labeled DNA probes (e.g., in a Southwestern blot).
126
What are the key clinical findings in homocystinuria?
127
What is the probability that a full sibling will be an identical HLA match?
1/4 (25%).
Each sibling has a 25% chance of inheriting the same HLA haplotypes from both parents, making them a full HLA match.
128
How is HLA matching between siblings determined?
HLA genes are inherited as haplotypes—clusters of linked genes on a single chromosome with a low crossover rate.
Each child inherits 1 HLA haplotype from each parent, so full siblings have a:
25% chance of being a full HLA match (same haplotypes)
50% chance of sharing one haplotype
25% chance of sharing none
129
What is the function of Release Factor 1 (RF1) in bacterial protein synthesis?
RF1 recognizes stop codons (UAA, UAG) on bacterial mRNA and terminates translation by promoting release of the newly synthesized polypeptide from the ribosome.
130
What is the function of small nuclear ribonucleoproteins (snRNPs) in eukaryotic cells?
snRNPs mediate splicing, a post-transcriptional modification in which introns are removed from pre-mRNA. This process does not occur in prokaryotes.
131
What is the inheritance pattern of sickle cell disease (HbSS)?
Autosomal recessive — the disease occurs when a person inherits two copies of the sickle cell gene (HbS)—one from each parent.
Carriers (HbAS) are typically asymptomatic and said to have sickle cell trait.
132
How do histones H1, H3, and H4 differ in structure and function?
133
What is the role of enhancer sequences in gene expression?
Enhancers bind activator proteins that bend DNA, helping them interact with general transcription factors and RNA polymerase II at the promoter. This increases transcription rates. Enhancers can be upstream, downstream, or far from the gene they regulate.
134
What is the role of silencer sequences in gene regulation?
Silencers bind repressor proteins that decrease transcription by preventing activation of RNA polymerase at the promoter.
135
What is the function of the CAAT box in transcription?
The CAAT and TATA boxes are promoter sequences found upstream of eukaryotic genes. They bind transcription factors and helps initiate transcription by stabilizing RNA polymerase binding.
