Exam 1 Flashcards
Nucleolus function
ribosome synthesis
G1 phase
first growth phase
s phase
DNA duplicated
G0 phase
cell resting period
CDK2-Cyclin E
G1/S checkpoint.
checks nutrients, growth factors, DNA damage and response to decide to divide
CDK1-Cyclin B
G2/M checkpoint.
checks cell size and DNA replication to commit to mitosis
Cyclin B 3
Late metaphase (spindle) checkpoint
Unregulated cell division
cancer
Mitotic inhibitors
Freeze cells in mitosis by inhibiting microtubule dynamics
Antimetabolites
Prevent cells from replicating DNA by inhibiting synthesis of thymidine
DNA damaging agents
damage DNA to overwhelm cancer cell because cancer cell might not have G2/M checkpoint that monitors for damage
Three types of chemotherapeutics
- mitotic inhibitors
- antimetabolites
- DNA damaging agents
Ion-channel linked receptor
Neurotransmitter binds to receptor and changes protein structure during signal transduction in a neuron
Enzyme linked receptors
cell surface receptors with intracellular domains
Juxtracrine
Signal producing cell makes direct contact with target cell
Endocrine
Signal-producing cells (endocrine cells) release signaling molecules (hormones) that act on distant target cells
Paracrine
Signal producing cells release signaling molecules that act on proximal cells (throwing skittles)
autocrine
signal producing cell is also the target cell
Myasthenia Gravis
Ion channel disfunction.
Autoimmune disease which the body makes antibodies against nicotinic acetylcholine receptor.
Prevents signaling at neuromuscular junctions resulting in muscle weakness
What method do half of all known medications use
GPCR
What is the basement membrane made of
basal lamina (made of lamina densa and lamina lucida with collagen fiber makeup), reticular lamina (reticular fiber makeup)
What type of diffusion happens in gas exchange
simple (passive)
Does facilitated diffusion require ATP
no
Carrier proteins
Bind molecules to be transported then change shape to release in facilitated diffusion
Forms of channel proteins
ligand gated, voltage gated, or always open
Why does sodium potassium pump pump out NA and in K
To maintain osmotic balance and cell volume
What causes cell differentiation
All cells have same DNA, It’s based on what parts of the DNA is read in each cell causing different genes to be expressed via proteins
Totipotent cells
Stem cell that gives rise to ANY cell type
Pluripotent cells
Stem cell that can five rise to all cells (endoderm, mesoderm, or ectoderm lineages) except the placental cells.
Multipotent
Stem cell that can only develop into a limited number of cells in that lineage
Hypertrophy
cells increase size, not number.
Pathologic enlargement of heart from hypertension.
Physiologic hormone induced in uterus during pregnancy
Hyperplasia
Cells increase in number.
Physiologic from hormones or increase in tissue masss after partial resection,
Pathologic from excess amount of growth factors or viral incfections
Atrophy
Reduced size of organ or tissue from decrease of cell size and number
Causes of atrophy
-Loss of endocrine stimulation (happens in menopause)
-Decreased workload of muscle
-Diminished blood supply
-Tumor exerting pressure
Extrinsic Apoptosis pathway
uses TNF receptor
Intrinsic Apoptosis pathway
Growth factor withdrawal, DNA damage, or protein misfolding sensed by Bcl-2 and mitochondria releases proapoptotic proteins
MitoA and Bendavia
Drugs used to reduce toxic reactive oxygen species in mitochondria
Cyclosporin A
Drug that inhibits mitochondrial permeability transition pore.
Used during immunosuppression, psoriasis, dry eyes, dermatitis, uticaria.
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List the three important types of bonds strongest to weakest
Covalent > Ionic > Hydrogen
List of monosaccharides
Ribose
Fructose
Glucose
Galactalose
List of Disaccharides
Lactose
Trehalose
Maltose
Disaccharide found in grain
Lactose
Disaccharide found in cow’s milk
Trehalose
disaccharide found in sunflower seeds, shrimp, and mushrooms
Maltose
Disaccharide found in grain
Sucrose
Disaccharide that is table sugar
Glycogen
Storage form of glucose.
Helps maintain blood-glucose levels
Starch
-Primary carb in diet
-Cellulose
-Branched is amylopectin
-Unbranched is amylose
Where is glycogen stored
liver and muscle
Liver importance with glycogen
Liver does the synthesis and degradation of glycogen
What lipids are used in signaling
Eicosanoids and hormones
What are the two essential fatty acids
- linoleic acid (omega-6 fatty acid)
- alpha-linolenic acid (omega-3 fatty acid)
Eicosanoid
2 carbon fatty acid used in signaling and gene regulation
Examples of eicosanoids
-Prostaglandins
-Prostacyclins
-Thromboxanes
-Leukotrienes
Prostaglandin
Eicosanoid used in inflammation
Prostacyclin
Eicosanoid that breaks up platelets
Thromboxane
Eicosanoid that causes platelet aggregation
Leukotrienes
eicosanoid that causes inflammation but causes pulmonary inflammation and anaphylaxes
What is the building block for steroid hormones
cholesterol
Bile salts
-Produced in liver from cholesterol
-Solubilize dietary fat in small intestines
What hormones are produced from cholesterol
mineralocorticoids, glucocorticoids, androgens, progesterone, estrogen
Vitamin D
-Acts as a hormone in the body
-cholesterol is converted to vitamin D with help of sunlight, liver, skin , and kidney
Calcitiol
Active form of vitamin D
Essential Amino Acids
Phenylalanine
Valine
Threonine
Tryptophan
Isoleucine
Methionine
Histidine
Lysine
Leucine
Transferin
Glycoprotein that transports iron
Protein function in homeostasis
Albuin helps with osmotic pressure.
Other proteins help with pH balance
How do proteins help with transport
Oxygen binds to hemoglobin
How are proteins used in signaling
As hormones and neurotransmitters
-ase
enzyme
enzymes that don’t end in “-ase”
trypsin, pepsin, thrombin
Competitive inhibition
inhibitor binds on enzyme’s active site so substrate can’t bind
Noncompetitive inhibition
inhibitor binds so site other than active site on enzyme causing active site to change shape and be unable to bind to substrate.
Allosteric regulation
Noncompetitive inhibition
What cells are actin and myosin found in
all of them
What does actin do
cell motility, wound healing, cytokinesis, skeletal muscle contractions, smooth muscle intercellular signaling,
Tubulin
Makes up microtubules, structural parts of flagella and cilia, non motile cilia (rods in eyes), mspindle fibers
Glycosaminoglycan
repeating disaccharide chains of modified glucose and/or galactalose
Glycosaminoglycans examples
Heparin, Chondroitin, Hyaluronic acid (longest)
Hyaluronic acid
Glycosaminoglycan. Extracellular matrix of joints, binds to collagen in cornea, and is a component of proteoglycan binding to collagen
Chondroiton
Glycosaminoglycan. Structural component and attachment point to collagen in joints and bones
Heparin
Glycosaminoglycan. Regulates immune response and blood clot formation from mast cells and liver cells.
What does purine cataboism cause
Uric acid –> Kidney Stones
What are the pyrimidines
Cytosine, Thymine, Uracil
What are the purines
Adenosine, Guanine
Nucleoside
Nitrogenous base + sugar. NO PHOSPHATE
Nucleotide
Sugar + nitrogenous base + phosphate group
What links nucleotides
Phosphodiester bonds making a phosphate backbone
Azidothymidine
Nucleoside analog of thymidine that is used in treating retroviral infections
Acyclovir
Nucleoside analog of guanosine.
Treats retroviral infection
mRNA
carries genetic code from DNA to ribosomes for translation
tRNA
Carries amino acids to location of protein synthesis
rRNA
combines AA to form proteins
P arm
Short arms of chromosome
Q arm
Long arms of chromosome
Telomer
End of arms of chromosome
Centromere
Middle of chromosome
Mitochondrial DNA
In a circle. From mom.
Introns
noncoding (only in eukaryotes)
Exons
Coding (in both prokaryotes and eukaryotes)
Histones
Proteins that function in the packaging of DNA.
Results in higher level of gene expression
Chromatin
Form of DNA packing
Heterochromatine
Highly condensed (packed)
10% of an interphase
Euchromatin
Less condensed, more extended state.
90% of interphase
X-chromosome inactivation
In females, one copy of X is packaged into heterochromatin and shut down. Which one is selected early in embryogenesis
What type of RNA is translated
mRNA
Gene
Segment of DNA that functions as a unit to generate RNA product
What direction is RNA sytnthesized
5’-3’
TFIID
Transcription factor
TBP (Tata-Binding-Protein)
Co activator to help get RNA polymerase onto the DNA for transcription
Binds to TATA box
RNA polymerase
enzyme that uses DNA as template to synthesize RNA molecule
Three main domains of mRNA
-Leader sequence
-Coding region
-Trailer sequence
Leader sequence
mRNA domain that starts with Guanosine cap at 5’ end
Coding region
mRNA domain from start codon to stop codon (termination signal)
Trailer sequence
mRNA domain that terminates at the 3’ end with a poly(A) tail.
RNA splicing
cutting out introns
Cap on 5’ end of RNA
-Guanosine
-Decreases rate of degradation
-Recognition site for binding of ribosome
Where does transcription occur
Nucleus
Where does translation occur
Cytoplasm
Where is rRNA produced
Nucleolus
What structure brings mRNA and tRNA together
ribosome
aminoacyl-tRNA
a three nucleotide codon (tRNA) attached to an amino acid made in aminoacyl-tRNA
A-site
aminoacyl site.
Binds appropriate aminoacyl-tRNA determined by codon=anticodon base pairing.
Where release factor binds to sto codon
P-site
Peptidyl site.
Binds to peptidyl tRNA
E-site
Ejection site,
Binds the tRNA without amino acid before it leaves the ribosomes.
Depurination
Spontaneous mutation.
Does not break phosphodiester backbone.
Results in loss of nitrogen base
Deamination
Spontaneous mutation,
Does not brak phosphodiester backbone.
Converts C–>U
X-rays effect on genome
Makes hydroxyl radicals that clave DNA strands
Huntington’s disease
Caused by trinucleotide expansion. Longer expansion means younger age of onset. Expansion of CAG sequence.
Resulting in
UV light effect on genome
Cause formation of pyrimidine dimers
Translocation
Chromosome breaks and reattaches segment to another chromosome
Xeroderma pigmentosum
Defect in nucleotide excision repair.
Unable to fix UV damage to genes.
High risk of skin cancer
Hereditary Nonpolyposis Colorectal Cancer
Lynch Syndrome.
Due to mutation of MSH2 or MLH1
Nonhomologus end joining
Most common mechanism for fixing double strand breaks.
Could introduce mutations.
Commonly used by cells in G1 phase.
When does Crossing over occur
After replication (G2-M)
Achondroplasia
Dwarfism.
Autosomal dominant mutation in fibroblast growth factor receptor (FGFR3)
Cystic Fibrosis
One of the most common autosomal recessive disorders.
Deletion in gene that encodes for chloride channel (CFTR) resulting in buildup of mucus in lungs, pancreatic insufficiency, and infertility
Hemophilia A
X-linked recessive mutation in blood clotting factor VIII
VItamin D-resistant rickets
X-lined dominant. Mutations in PHEX gene effecting phosphate balance.
Fragile X Syndrome
Trinucleotide expansion of CGG in FMR1 gene.
Intellectual disability
Ataxia Telangiectasia
Mutated ATM impairs DNA damage response.
Susceptible to double stranded breaks
DNA methylation
Turning off a gene
What cell cycle checkpoint is most critical
G1/S (CDK4/6-CyclinD, CDK2-Cyclin, p53)
Tumor suppressor
The “brakes” of the cell cycle. (ex. p53, Rb)
protooncogene
Noncancerous cells that drive the cell cycle forward. (ex. Cyclins)
Anti-apoptosis protein examples
Bcl-2
Bcl-XL
Mcl-1
Pro-apoptotic proteins examples
NOXA, PUMA, BAX, BIM, BID
Number one contributor to cell immortality
Cancer cells activate telomerase to keep telomeres long
VEGF
Vascular Endothelial Growth Factor secreted from tumors to promote blood vessel formation
Epithelial-Mesenchymal Transition
Cancer cells acquire abiliity to migrate by MMPs facilitating invasion through extracellular matrix. and disabling e E-Cadherin
E-cadherin
Protein that holds cells together so stuff can’t get through extracellular matrix
Where do solid tumors originate
Carcinomas originate from endothelium (endoderm or ectoderm)
Sarcomas originate from mesenchymal cells (mesoderm
Where do liquid cancers originate
Bone marrow
Examples of liquid cancer
Leukemias
Multiple Myelomas
Lymphomas
DNA methylation
Silences tumor suppressor genes
What do non-coding RNAs do
Regulate oncogenes and tumor suppressors
Tumor suppressor mutation
Autosomal Recessive
Loss of functoin
oncogenes
Mutated forms of proto-oncogenes
Autosomal dominant
Gain of function
TP53
Tumor suppressor gene
Mutation in this gene causes 50% of all cancer by disabling p53
Caretaker gene
Involved in genomic repair and genome stability/integrity
Caretaker gene mutation
Causes loss of function
Causes aneuploidy
Caretaker gene example
BRCA-1
General sequence of tumorigenesis
- Oncogene activation
- Mutation accumulation
- Tumor suppressor gene inactivation
- complete loss of growth control
PDL-1
Expressed on cancer cells to make it invisible to immune system
Cancer Associated Fibroblasts
Promote tumor growth through secretion of growth factors and remodeling of extracellular matrix
Warbug Effect
Tumor prefer glycolysis over oxidative phosphorylation even if oxygen present allowing for rapid ATP production and intermediates for biosynthetic pathways
BRCA 1/2 mutations
Increased risk of breast and ovarian cancers
Kinases
Enzyme that phosphorylate proteins
Phosphatase
Enzyme that takes off phosphate
RAS pathway
-GF binds to RTK receptor activating RAS (G protein)
-RAS phosphorylates/activates RAF
-RAF phosphorylates/activates MEK
-MEK phosphorylates/activates ERK
-ERK regulates transcription factor in the nucleus
What happens when there is a mutation in RAS
Cell is constantly told to divide even if no GF present.
What happens when there is a BRAF mutation
MEK-ERK always activated. Most common in thyroid cancer
PI3K pathway
-Growth factor binds to RTK receptor activating PI3K
-PI3K converts PIP-2 to PIP-3.
-PIP3 activates AKT
-AKT activates mTOR
-mTOR promotes proliferation
WNT/B-Catenin pathway
-WNT bind to GPCR inhibiting B-catenin destruction complex (APC) allowing B-catenin to accumulate in cytoplasm and translocate to nucleus
-B-catenin activates transcription factors in nucleus promoting proliferation
Retinoblastoma
-Childhood eye cancer in retinal tissue.
-Caused by gene mutation that causes person to not have Rb protein (tumor suppressor)
How does colon cancer happen
APC mutation in WNT/B-catenin pathway.
Epithelial cells can’t shed, so cells bunch up forming polyps (hyperplasia.
This causes continued mutations
What is the guardian of the genome
P53
P21
Tumor suppressor at G1/S checkpoint and G2/M checkpoint.
Transcribed by p53.
Binds and inhibits CDK Cyclin halting the cell cycle to give time to repair DNA
PTEN
Inhibits PI3K/AKT signaling pathway.
Loss of PTEN leads to unregulated cell growth.
Apoptosis pathway
-pro-apoptotic proteins more present than anti
-Cytochrome C released from mitochondria
-Caspase 9 activated
-Apoptosis
Metastasis steps
-Invasion
-Detatchment
-Intravasation
-Circlation
-Extravasation
-Colonization
