Drugs & Diseases Flashcards
Deficiency of Lysyl Hydroxylase, pro collagen peptidase
Stretchy skin, hyper mobile joints and weaken blood vessels
Mutation in AA sequences of collagen Type III (I or V)
Collagen not secreted; either degraded or accumulated
Ehlers-Danlos Syndrome
What are the causes of scurvy?
Vitamin C deficiency; ascorbate
No hydroxylation reactions; no cross-linking
Loose teeth, bruises on limbs; fragile capillaries
Problem behind Osteogenesis imperfecta Type I
Which type is Lethal?
Easy fracturing and bending of bones; 50% of collagen is normal
Null allele for pro-collagen alpha 1
Type II
Main disorder for Osteogenesis imperfecta Types II, III, and IV
Substitution of a Glycine with a more bulky Amino acid residue
No propagation of triple helix, mutations close to C-terminus more severe
Easy bending and fracturing of bones, slow wound healing and twisted spine
Expansion of CGG trinucleotide repeat in 5’UTR of FMR 1 gene
Also extensive methylation of FMR1 promoter
Most common form of mental retardation
Fragile X syndrome
Fragile X syndrome
Most common form of mental retardation
Expansion of CGG trinucleotide repeat in 5’UTR of FMR1 gene
Also extensive methylation of FMR1 promoter
Rett Syndrome
Inappropriate activation of methylated genes
Autism spectrum disorder mainly in females
Mutations in X linked MECP2 (methyl CpG binding protein 2) which normally binds and silences methylated genes
X-linked dominant; males miscarried, therefore mainly in females
Which syndrome causes inappropriate activation of methylated genes, caused by mutations in X linked MECP2 (methyl CpG binding protein 2) that normally binds and silences methylated genes
Rett Syndrome
X-linked dominant; mainly in females; males are miscarried
Alpha-amanitin “death cap” mushroom function
Binds euk RNA polymerase, inhibiting DNA tx
RNA pol II
Transcribes protein coding genes
Makes mRNA
Method of action for Rifampin
Binds to beta subunit of prok RNA polymerase
Stops transcription initiation
Used to treat tuberculosis
Action of Actinomycin D
Antibiotic
Inhibits Tx
Binds DNA template, not allowing for RNA pol to move along the strand
Tetracyclin
Streptomycin
Erythromycin
Chloramphenicol
All disrupt what process?
Prok Translation
Cyclohexamide
Pseudomonas toxin
Diphteria toxin
All inhibit which process?
Euk Translation
Method of action of Shigella toxin
Binds to A site on euk ribosome, preventing aminoacyl tRNA binding, thereby preventing protein synthesis in translation
Method of action of Shigella toxin
Binds to A site on euk ribosome, preventing aminoacyl tRNA binding, thereby preventing protein synthesis in translation
What are the two categories of chromosome abnormalities?
- Structural
2. Numerical
What are the categories for numerical chromosome abnormalities?
- Aneuploidy; single chromosomes (monosomy, trisomy, tetrasomy)
- Polyploidy; complete sets of chromosomes (triploidy, tetraploidy)
What are the categories of structural chromosome abnormalities?
- Translocation
- Inversion - two breaks in same chromosome w/ reversal of order of segment
- Deletion - results in unbalanced karyotype; partial monosomy; offspring will have too much info and not
- Insertion
- Rings
- Isochromosomes
Robertsonian Translocation
Two non-homologous Acrocentric chromosomes break at centromere and long arms fuse, while short arms are usually lost
No change in chrom. Number or risk to carriers
What cytogenetic abnormalities are most common in live born infants?
Trisomies XXY, XYY, and XXX
What are the most common cytogenetic abnormalities in spontaneous abortions?
Monosomy X
Klinefelter syndrome
Karyotype
Phenotype
47, XXY
Nondysjunction at anaphase
Learning difficulties Testicular atrophy Gynecomastia - breast dev. Female hair distribution Barr body present Hypogonadism
47, XYY Syndrome
Tall Muscular Subnormal IQ Attention deficit Hyperactivity
Trisomy XXX
Not phenotypically abnormal
Which chromosome abnormality results in phenotypically normal?
A. Turners syndrome B. Klinefelter syndrome C. Trisomy X D. 47, XYY E. Trisomy 21
C. Trisomy X; XXX
Turner Syndrome
Karyotype
Genotype
Edema of the feet
Discolored sports
Narrowing of the aorta
Avg. Or Above normal IQ
‘Menopause before menarche’ = increased LH & FSH
Spontaneous abortion
Deficiency in spatial perception & fine motor skills
Down syndrome
Trisomy 21; most common
Moderate Mental retardation
Can be due to Robertsonian translocation but mainly nondysjunction
Flat nasal bridge Low set folded ears Short neck with loose skin on nape Epicanthal folds (inner corner of eye) Brushfield spots around margin of iris "Simian crease" on hand Congenital heart disease in 1/3
Edward syndrome
Trisomy 18
47, XY +18 or 47, XX +18
List the 3 main categories of genetic disorders
- Single gene disorders
- Chromosome disorders
- Disorders of complex inheritance
What is the base substitution for sickle cell disease?
Mendelian Inheritance
T substituted for an A in coding strand of DNA
= Valine substituted for Glutamic Acid; Glu6Val; E6V
Valine = neutral; Glutamic acid = charged; phobic
Affects beta subunit of Hb
Clinical features of sickle cell disease
(Mendelian Inheritance)
Hemolytic anemia Dehydration Deoxygenation Red cells sickle under conditions of low O2 tension Hypoxia
Affects beta subunit of Hb
Phenylketonuria
Deficiency of phenylalanine Hydroxylase
Autosomal recessive
Treated by following strict diet after birth
Elevated phenylalanine in tissues, plasma, urine
Mental retardation
Failure to walk and talk
Hypopigmentation (lack of tyrosine)
Symptoms: Hypopigmentation, mental retardation, elevated phenylalanine in urine, tissues, and plasma.
PKU; Phenylketonuria
Complete loss of branched chain alpha-keto-acid dehydrogenase
Elevated levels of Leu, Ile, Val = which are hydrophobic; accumulation has toxic effects on the brain
Vomiting, dehydration, feeding problems
Metabolic acidosis
Maple Syrup Urine Disease
Maple Syrup Urine Disease
Complete loss of branched chain alpha-keto-acid dehydrogenase
Elevated levels of Leu, Ile, Val = which are hydrophobic; accumulation has toxic effects on the brain
Vomiting, dehydration, feeding problems
Metabolic acidosis
Most common symptoms of mitochondrial disorders?
Progressive muscular weakness Retinitis pigmentosa Hearing loss Ataxia Heart muscle deterioration
Phenotypic expression = directly related to amount of mutated mtDNA in a cell
What type of disorders stem from:
Progressive muscular weakness Retinitis pigmentosa Hearing loss Ataxia Heart muscle deterioration
Mitochondrial disorders
What type of transport is Coatomer-coated transport?
A vesicular transport that moves materials between the RER and the Golgi
Anterograde = RER --> Golgi; COPII Retrograde = Golgi --> RER; COPI
Vesicular transport is used to transport what type of substances?
LARGE; whereas transmembrane proteins are used for small, hydrophilic substances with or against their [gradient]. (ATP pumps, Channels, Transporter/Carriers)
Where in the body can you find caveolin-coated vesicles?
Endothelial and Smooth muscles cells
List the three types of vesicular transporters
- Clathrin-coated; dynamin (receptor mediated endocytosis)
- Coatomer-coated; COPII and COPI
- Caveolin-coated; endothelial and SM cells
Where are cilia found?
Epithelial cells of the respiratory tract and oviduct of female genital tract
Contain microtubules
Which of the following cell organelles contain no membrane?
A. Microtubules, Centrioles, Ribosomes B. Ribosomes, centrioles, mitochondria C. Lysosomes, ribosomes, mitochondria D. Vesicles, centrioles, Microtubules E. Microtubules, peroxisomes, mitochondria
A. Centrioles, microtubules, ribosomes
3
Which part of mitochondria contain cristae?
A. Outer membrane B. Inner membrane C. Inter-membrane space D. Mito matrix E. Outer and Inner membrane
B. Inner membrane
Cristae increases SA
Cytochrome c of mitochondria is located in what part of mitochondria?
A. Outer membrane B. Inner membrane C. Inter-membrane space D. Mito matrix E. Outer and Inner membrane
C. Inter-membrane space; apoptosis
Which part of mitochondria contain cristae?
A. Outer membrane B. Inner membrane C. Inter-membrane space D. Mito matrix E. Outer and Inner membrane
B. Inner membrane
Cristae increases SA
Cytochrome c of mitochondria is located in what part of mitochondria?
A. Outer membrane B. Inner membrane C. Inter-membrane space D. Mito matrix E. Outer and Inner membrane
C. Inter-membrane space; apoptosis
List the two classes of cell surface receptors
- Ion-channel-linked receptors; (transmitter-gated ion channels) i.e. Synaptic signaling; dimer
- Enzyme-linked receptors; single-pass; ligand-binding site = extracellularly + catalytic site intracellularly
Define potentiality
A cell’s capacity for giving rise to cells of other types
Cause of beta-thalassemia
Defective mRNA splicing
Define pleomorphism
A property of anaplastic cells (cancerous)
Cells that display hyperchromatic nuclei (deeply stained)
High nuclear to cytoplasm ratio (1:1 rather than 1:4)
High mitotic rate, NO cellular adhesion
Characteristics of anaplasia cells
- Loss of differentiation
- Backward growth to embryonic cells
- Pleomorphism; no adhesion, greater mitosis, large nucleus:cytoplasm ratio (1:1 instead of 1:4), hyperchromatic nuclei (deeply stained purple)
List the three types of cells
Love.Peace.Sex
- Labile; skin cells, susceptible to neoplasia
- Permanent; quiescent until stimuli comes = highly mitotic; susceptible to neoplasia
- Stable; nonproliferative; resistant to neoplasia
