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gene expression/ transcription
rosalind franklin = real DNA hero
transcription DNA sequence is enzymatically copied by an RNA polymerase to produce mRNA
- transcription = price that leads to translation of genetic code into a functional peptide or protein
- DNA is unwound by DNA helices
- RNA polymerase binds and recognizes the start site
- RNA nucleotides (uracil rather than thymine) base pair with the DNA
- form chain of mRNA
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Transcription
- transcription factors
- proteins that assist the RNA polymerase in recognizing promoters
- transcription factors are divided into 2 types
- 1. gene specific transcription = activate specific genes
- ex. estrogen receptors = estrogen target gene specific
- 2. general transcriptions factors = required to activate all genes
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regulation of CREM and transcription
cAMP response element modulator - CREM is a transcription factor
- CREM null mice = infertile
- CREM required to make sperm
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DNA to protein
- 1 gene activation
- 2.transcription
- 3.mRNA processing
- 4. translation
- 5. post-translational modification
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membrane transporters
- Channel proteins (create a water filled pore)
- can be classified into:
- 1. gated channels
- 2. open channels
- Carrier proteins (never form an open channel between the 2 sides of the membrane)
- can be classified into
- 1. uniport carriers (Glu goes thru)
- 2. symport carriers (Na and Glu go thru)
- have cotransporters
- 3. antiport carriers (Na goes in and K goes out)(ATP needed)
- have cotransporters
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active transport processes
require energy (ATP) from cells
- Transport by pumps
- pump are membrane transporters that move a substance again the concentration gradient
- ex. Ca pumps, Na-K pumps
- Transport by vesiclesallows substances to enter or leave the interior of a cell without actually moving through its plasma membrane
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Primary active transport
- Extracellular fluid
- ↑ Na and ↓K
- Intracellular fluid
- ↓ Na and ↑ K
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secondary active transport
- Mecanism of the SGLT transporter
- 1. Na binds to the carrier
- 2. Na creates a site for Glucose
- 3. Binding of glucose changes the carrier confirmation
- 4. Na is released into the cytosol. Glucose follows
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epithelial transport
- epithelium is either leaky or tight
- capillaries - all dissolved molecules can pass through
- kidney - held by tight barrier
- substances must enter cell and pass through it
selectively regulates exchanges of ions and nutrients
- absorptions = from external to internal
- secretion = from internal to external
transporting epithelial characteristics = thicker membrane modifications, cell junctions, mitochondria
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secretory epthelium
- exocrine glands = release into the external environment, skin, airways, digestive
- release into ducts
endocrine glands = release hormone into the blood stream
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transcytosis across the capillary endothelium
- 1. plasma proteins are concentrated in the caveolae, which then undergo endocytosis and form vesicles
- 2. vesicles cross the cells with help from the cytoskeleton3. vesicle contents are released in the interstitial fluid by exocytosis
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cystic fibrosis case study
- alvins symptoms:
- chronic cough, diarhea, wheeze
- runny nose
- SALTY SKIN
pathophysiology of CF = characterized by defective epithelial ion transport
- abnormal transport of Cl and Na across epithelium in all exocrine tissues, leading to think viscous secretions in the lungs, pancreas, liver, intestine and reproductive tract
- ↑ salt content in sweat glands secretions
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what are the genetic and molecular causes of CF?
- faulty gene = on chromosome 7
- malfunction of gene coding for the CF transmembrane conductance regulator (CFTR)
- malfunction leads to defective cAMP activated Cl-Na channel on the surface of epithelial cells
- NaCl becomes trapped in cell
- pulls the water in and results in dehydrated mucus
- lungs are the most affected organs
- 70-80% of patients lack receptor?*
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what are the accepted treatments for children and adults with CF?
- airway clearance therapy
- antibiotics
- bronchial dilators
- vitamin supplements
- enzyme to aid digestion
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different classes of proteins
- structural proteins
- enzymes
- membrane receptor proteins
- transporterschannel proteins
- carrier porteins
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membrane receptor
ligand = binds to a cell membrane receptor protein
ligand-receptor complex = triggers intracellular response
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vesicule transport
- Phagocytosis
- cell engulfs bacterium or other particle into phagosome
- Endocytosis
- the plasma membrane "traps" some extracellular material and brings it into the cell in a vesicle
- active process that can only be non selective (pinocytosis) or highly selective
- potocytosis = uses cavaolae
- receptor mediated uses clathrin coated pits
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what are the 2 types of endocytosis?
- 1. Phagocytosis
- "condition of cell eating"
- large particle are engulfed by the plasma membrane and enter the cell in veiscles
- vesicles fuse with lysosomes, where the particles are digested
- 2. Pinocytosis
- "condition of cell drinking"
- fluid and substances dissolved in it enter the cell
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receptor mediated endocytosis
- 1. ligand brings to receptor
- 2. receptor ligand migrates to clathrin coated pit
- 3. endocytosis
- 4. vesicle loses clathrin coat
- 5. receptors and ligands separate
- 6. ligands go to lysosome or Golgi for processing
- 7. transport vesicle with receptors
- moves in the cell membrane
- 8. transport vesicle and cell membrane fuse (membrane recycling)
then it restarts again
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active transport exocytosis
- Exocytosis
- process by which large molecules love the cell even though they are too large to move out through the plasma membrane
- enclosed in many vesicles, pulled by the cytoskeleton to the plasma membrane, where the contents are released
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