SFM Quiz 2 Flashcards
the storage site of lysosomal hydrolases No digestive events Homogenous Inactive enzymes
primary lysosomes
engaged in a catalytic process digestive enzymes heterogenous active enzymes
secondary lysosomes
Cholesterol uptake disrupted Characterized by elevation of LDL, the predominant cholesterol transport protein in the plasma
familial hypercholesteremia
absence or reduced number of peroxisomes congenital
Zellweger spectrum disorder
Binds to 30S subunit and interferes with the binding of fmet-tRNA and impairs initiation. Interferes with 30S subunit association with 50S subunit.
Streptomycin
binds to large 50S subunit, blocking translocation of the ribosome.
Clindamycin, Erythromycin
binds to small 30S subunit, blocks entry of aminoacyl-tRNA to ribosomal complex and impairs elongation.
Tetracycline
inhibits peptidyl transferase activity and impairs peptide bond formation.
Chloramphenicol
binds to large 60S subunit (euk.), blocking entry of aminoacyl-tRNA to ribosomal complex.
Shiga toxin, Ricin
inactivates GTP-bound EF-2, interfering with ribosomal translocation (euk.)
Diptheria toxin
inhibits peptidyl transferase (euk.) and impairs peptide bond formation.
Cycloheximide
causes premature chain termination (prok/euk). Resembles the 3’ end of the aminoacylated-tRNA. Enters the A site and adds to the growing chain. Forms a puromycylated chain, leading to premature chain release. More resistant to hydrolysis. Stops the ribosome from functioning.
Puromycin
does not change the amino acid.
silent mutation
changes amino acid in the protein with either no effect on protein function or a protein with vastly different function.
missense mutation
codon changes into a stop codon causing premature chain termination. Also called null mutation. Protein either degraded or formed as a truncated version.
nonsense mutation
one or more nucleotides are deleted or inserted into ORF. Out of frame causes change in the codon sequence and consequently alteration in the amino acid sequence of the protein (E.g., Duchenne Muscular Dystrophy, beta thalassemia)
frameshift mutation
Arises from a missense mutation of 6th codon in the allele of the gene for human β-globin (HBB),
Sickle cell anemia
Sickle cell anemia initial amino acid: Sickle cell anemia altered amino acid:
Glutamic acid Valine
out-of-frame (OOF) deletion to the dystrophin gene leads to partially or non-functioning dystrophin protein. leads to muscle wasting
Duchenne Muscular Dystrophy (DMD)
In-frame deletions result in expression of truncated forms of dystrophin, giving rise to a milder form of the disease
Becker muscular dystrophy
Translocation signal: cytoplasm
None
Translocation signal: Mitochondria
N-terminal hydrophobic alpha-helix HSP-70= chaperone through TOM->TIM->matrix
Translocation signal: Nucleus
KKKRK signal Nuclear pores
Translocation signal: Peroxisome
C-terminal SKL
Translocation signal: ER lumen
C-terminal KDEL SRP wraps around ribosome-mRNA-peptide complex=stop translation Luminal enzymes cleave signal=released
Translocation signal: Lysosome
M-6-P (I-cell disease)
Translocation signal: secretion
tryptophan rich-domain
Translocation signal: membrane
N-terminal apolar
Tagging of lysosomal proteins with mannose 6P is defective. Proteins not targeted to lysosomes. High plasma levels of lysosomal enzymes. By 6 months: failure to thrive and developmental delays and physical manifestations. Development delays of motor skills more pronounced than cognitive delays. Abnormal skeletal development, coarse facial features, restricted joint movement, stiff claw-shaped hands, short-trunk dwarfism, clouding on the cornea. Hepatomegaly, splenomegaly, defective heart valves. Recurrent respiratory tract infections: (pneumonia, otitis media bronchitis). Death frequently occurs by age 7, usually due to congestive heart failure or recurrent respiratory tract infections.
I-cell disease
O-link glycosylation
hydroxyl group: Serine, Threonine
N-link glycosylation
Asparagine Transferred from phospho Dolichol
Formation of an ester bond between phosphate and OH of an amino acid.
Phosphorylation
Formation and reorganization of these bonds occur in ER lumen.
Disulfide bonds
Lysines in collagen modified to form 5-hydroxylysines, further glycosylated with addition of glucose and galactose. Some lysines deaminated to aldehydes Some prolines hydroxylated to hydroxyprolines. Modifications important for assembly of collagen What vitamin is mandatory for lysyl and prolyl hydroxylases?
vitamin A Ascorbic acid
overly flexible joints, walls of blood vessels, intestines or uterus may rupture
Ehlers-Danlos syndrome
blisters on skin
Epidermolysis Bullosa Simplex
Amyloid precursor protein (APP) breaks down to form amyloid beta peptide (Aβ). Misfolding/Aggregation of Aβ forms plaques in brain (extracellular). Hyperphosphorylation of Tau (neurofibrillary tangles) (intracellular).
Alzheimer’s disease
Aggregation of α-synuclein (AS) protein forms insoluble fibrils which deposit as Lewy bodies in dopaminergic neurons in substantia nigra. Results in selective death of these neurons. Symptoms due to reduced availability of dopamine.
Parkinson’s disease
Mutation in Huntingtin gene results in expansion of CAG triplet repeats. Results in Polyglutamine repeats in abnormal Huntingtin protein. Forms intramolecular H-bonds, which eventually misfold and aggregate. Selective death of cells in basal ganglia cause the symptoms.
Huntington’s disease
Caused by misfolding of prion proteins. Transmissible – infection by misfolded proteins converts normal proteins to misfolded form. Belongs to Transmissible spongiform encephalopathies (TSEs). Spongiform - appearance of infected brains, filled with holes and resemble sponges under a microscope.
Creutzfeldt-Jakob disease (HD)
Autosomal Dominant Inheritance
Postaxial polydactyly
Autosomal Recessive Inheritance
Tyrosinase-negative Albinism
X-linked recessive inheritance
Duchenne Muscular Dystrophy
Degeneration of retinal ganglion cells Caused by one of three pathogenic mtDNA point mutations affecting NADH dehydrogenase Starves RGCs of energy, making them unable to transmit signals to the brain. Acute or subacute loss of central vision Typically early teens or 20’s Inter-eye delay of 8 weeks
Leber’s hereditary optic neuropathy (LHON)
Caused by a mutation in the gene encoding for tRNA for lysine, which disrupts the synthesis of cytochrome-c oxidase Patients present with myoclonus dinated muscle movement (ataxia) and seizures Particularly affects the muscles and nerves Large variability of presentation due to heteroplasmy
Myoclonic epilepsy and ragged red fibers (MERRF)
Most common maternally-inherited mitochondrial disease Affects many body systems, particularly brain nervous system, and muscles Stroke and dementia Diabetes, deafness, cognitive impairment, short stature, migraine
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS)
X-linked dominant inheritance
hypophosphatemia
two chromosomes are inherited from the same parent, they will have parent-specific imprinting No gene product
Uniparental disomy
For some human genes, one of the alleles is transcriptionally inactive (no mRNA produced) Depending on the parent from whom the allele was received
Genomic imprinting
Long arm of two acrocentric chromosomes combined, short arm typically is lost
Robertsonian translocation
Karyotype: 45, XO Monosomy X Female (no Y) Short stature Ovarian hypofunction/premature ovarian failure Many do not undergo puberty Most are infertile ~30% webbed neck Low hairline on neck CV defects No cognitive defects
Turner Syndrome
Deletion of a region of chromosome 15 Phenotype depends on if deletion is on paternal or maternal chromosome
Prader-Willi and Angelman Syndromes
Short stature, hypotonia, small hands/feet, obesity, mild to moderate intellectual disability, uncontrolled eating
Paternal = Prader-Willi Syndrome
Severe intellectual disability, seizures, ataxic gait
Maternal= Angelman Syndrome
Karyotype: 47, XXY Varying presentation Varying degrees of cognitive, social, behavioral, learning difficulties Primary hypogonadism (low T) Small and/or undescended testes Gynecomastia, infertility Tall stature Variability in X numbers can increase symptoms (48, XXXY; 49, XXXXY)
Klinefelter syndrome
(47, XX +21) Most common (1 in 700 pregnancies) Strongly associated with increased maternal age Results most commonly from maternal meiotic nondisjunction (in the ovum) Also due to unbalanced translocation 46, XX der(14:21)(q10;q10)+21 (only 4% occurrences) Varying degrees of cognitive impairment Structural abnormalities: increased nuchal translucency, cardiac defects, duodenal atresia, ventriculomegaly, absent nasal bone, short limbs
Trisomy 21 Downs Syndrome
(47, XX +18) 1 out of every 6000 births Often IUGR 95% die in utero <10% of live births survive to 1 year Microencephaly, prominent occiput, malformed and low-set ears, small mouth and jaw, cleft lip/palate, rocker bottom feet, overlapped fingers
Trisomy 18 Edwards Syndrome
(47, XX +13) Severe developmental abnormalities 1 out of every 12,500 births Most die before birth Most perinatal death within 1 week (13% of live births survive to 10 y.o.) Heart abnormalities, kidney malformations, CNS dysfunction Microcephaly, malformed ears, closely spaced/absent eyes, clenched hands and polydactyl, cleft lip/palate
Trisomy 13 Patau Syndrome
The frequency a gene manifests itself
Penetrance Retinoblastoma
Describes the range of phenotypes that vary between individuals with a specific genotype
Variable expressivity
Patients have café-au-lait spots – pigmented areas the color of coffee with cream Spots differ in number, shape, size and position
Neurofibromatosis
Affects the connective tissue, subsequently many different systems Ectopia lentis, weakened and stretched aorta May lead to an aneurysm and aortic dissection
Marfan syndrome
Single disorder, trait, or pattern of traits caused by mutations in genes at different chromosomal loci Only one mutant locus is needed for the phenotype to manifest.
Locus Heterogeneity
Brittle-bone disease (7/100,000) Mutations in collagen genes (two loci: chromosome 7 and 17), either mutation exhibits similar phenotypes (varying severity)
Osteogenesis Imperfecta
mating’s are more likely to produce offspring affected by rare autosomal recessive disorders
Consanguinity
traits in which variations are thought to be caused by the combined effects of multiple genes when environmental factors cause variation in the trait
Polygenic Multifactorial
For multifactorial diseases that are either present or absent, it is thought that a ____ must be crossed before the disease is expressed
threshold of liability
muscular hypertrophy between stomach and duodenum Leads to vomiting and obstruction Five times more common in males than females Males need less risk genes to show disease; females need more risk genes
Pyloric Stenosis:
Ability to give rise to all cells of an organism, including embryonic and extraembryonic tissues (placenta).
Totipotency
Ability to give rise to all cells of the embryo and subsequently adult tissues. (embryonic stem cells)
Pluripotency
Ability to give rise to different cell types of a given lineage. (adult stem cells)
Multipotency
Proportions of body parts are determined early Each tissue has fixed number Programmed to have fixed number of divisions Controlled by short range signals that operate for a few hundred cell diameters Define the size of large final structures
founder stem cells
cells that divide frequently Transit from a cell with stem cell characteristics to a differentiated cell Leave the basal layer and incorporate into the layers above Programmed to have limited number of divisions finite Part of strategy for growth control Committed
Transit Amplifying Cells
asymmetric division may create 2 cells, one with stem cell characteristics and another with factors that give it the ability to differentiate
Divisional Asymmetry
Division makes 2 identical cells but environment may influence/alter 1 cell
Environmental Asymmetry
Some tissues’ stem cells selectively retain original DNA A way to prevent genetic errors in stem cells This daughter cell will retain stem cell characteristics Original strand of DNA preserved in stem cells from generation to generation Second cell gets the newly synthesized strand
immortal strand hypothesis
Derived from the blastocyst stage of embryo Capable of proliferating indefinitely in culture Unrestricted developmental potential When put back in blastocyst they can integrate well with the embryo Develop into different cell types If injected into an embryo at a later stage or into an adult they fail to receive appropriate sequence of cues for proper differentiation Can become a tumor
embryonic stem cells
Transcription factors essential for establishment and maintenance of pluripotent stem cells in the embryo
Nanog, Oct4, Sox2 and FoxD3
required for early stages of pluripotent cell differentiation
GCNF
growth factors found in pluripotent cells
Cripto and GDF-3
nucleus taken from somatic cell of patient and injected into oocyte of a donor replacing the ooctye nucleus Blastocyst generated from this hybrid oocyte and ES cells isolated
Somatic cell nuclear transfer
4 gene regulatory factors
Oct3/4, Sox2, Myc and KIf4
: signal (hormone) is transported via blood. Example epinephrine Long-distance signaling Epinephrine released by adrenal medulla and acts on heart muscle Long-lasting: half-life on minute scale Freely diffusing signal
Endocrine
: signal diffuses to neighboring target cell of a different cell type. Example testosterone Leydig cells synthesize and secrete testosterone which induces spermatogenesis by acting on Sertoli and germ cells Local signaling Short-lived signal
Paracrine
secreting cells express surface receptors for the signal. Example interleukin-1 Or release to cells of the same type Common in chemokines: interleukin-1 produced by T-lymphocytes promote their own replication during an immune response Action of Growth Factors in cancer cells
Autocrine
signal binds to signaling cell which then binds to receptor on the target cell. Example heparin-binding epidermal growth factor Heparin-binding epidermal growth factor-like growth factor (HB-EGF) binds to EGF receptor In immune cells
Direct/Juxtacrine
Drop in Hormone levels: -decreased adenylyl cyclase activity - decreased cAMP - decreased PKA activity Remove the signaling molecule: phosphodiesterase will remove cAMP/cGMP Receptor sequestration: endosome Receptor destruction: endosomes + lysosomes (proteases)
Signal desensitization
- Signal molecule
- GPCR
- PLC-> PIP3-> IP3 (Ca+2 channel and PKC) + DAG (PKC=phosphorylation of proteins)
- Ca+2-calmodulin complex=activation of proteins (ex. CAM kinase, MLC kinase)
Gq-phospholipase C ex. Acetylcholine
- Light 2. GPCR 3. cGMP PDE: cGMP-> 5’-GMP
Gt-cGMP phosphodiesterase
- Signal molecule 2. GPCR 3. AC: ATP->cAMP (inactive->active PKA=phosphorylates proteins) 4. PDE: cAMP->AMP
Gs- stimulate adenylate cyclase ex. Epinephrine (beta), Histamine
- Signal molecule 2. GPCR 3. GTPGialpha=no AC cAMP production
Gi- inhibits adenylate cyclase ex. Epinephrine/Norepinephrine (alpha), Dopamine
Inhibitors of cGMP PDE
increase cGMP=Viagra increase cAMP=caffeine
Covalent modification of α subunits of Gs ADP ribosylation of Arg in Gs α decreases intrinsic GTPase activity Gsα remains active (GTP bound form) and continuously stimulates adenylate cyclase, resulting in overproduction of cAMP
Cholera toxin
prevents the activation of GiαADP ribosylation of Cys on Giα prevents activation and dissociation of α subunit from the trimeric G protein complex Less inhibition of AC and hence overproduction of cAMP
Pertussis toxin
diffuses to neighboring muscle and activates guanylate cyclase, leading to the production of cGMP. cGMP produced from activated guanylate cyclase results in smooth muscle relaxation and vasodilation. Nitroglycerine and other nitrates (the medicines taken by patients with angina) decompose to form NO and help to lower blood pressure.
Nitric oxide
lipophilic compounds that block the effects of histamine to the H1 GPCR
antihistamines
condition marked by growth of tumors in nerve tissue. Caused by inactivating mutation in ____ gene, ___ uncontrollably activated pathways for nerve tissue growth. Optical glioma, macrocephaly, learning disabilities
Neurofibromatosis GAP
breast cancer drug ___ targets HER2, which belongs to the family of EGF-binding ___
Herceptin RTKs
both probe and target nucleic acid are DNA probe is single stranded DNA and target is mRNA
Southern Blotting Northern Blotting
Normal β-globulin allele has __ DdeI restriction sites Patients with sickle cell only have __ restriction sites
3 2