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115 Cards in this Set
- Front
- Back
How can enzyme concentrations be altered for enzyme regulation?
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By synthesis/destruction
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What is an example of covalent modification that regulates enzymes?
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Phosphorylation
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What are some enzymes that undergo proteolytic modification as a method of their regulation?
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Zymogens
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What is allosteric regulation of enzymes illustrated by?
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Feedback inhibition
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What proteins are capable of transcriptional regulation of enzymes?
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Steroid hormones
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What are the phases of the cell cycle?
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G1, S, G2, M
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What is the SHORTEST phase in the cell cycle?
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Mitosis!
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What does Mitosis consist of?
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-Prophase
-Metaphase -Anaphase -Telophase |
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What phases are of VARIABLE duration?
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G0 and G1
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What regulates the checkpoints that control transitions between phases?
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-Cyclins
-CDKs -Tumor suppressors |
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What is the guardian of the genome?
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P53 tumor suppressor gene
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What are PERMANENT cells?
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Cells that remain in G0 and are terminally differentiated. Can't back out.
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What are 4 examples of Permanent cells?
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-Neurons
-Cardiac muscle -Skeletal muscle -RBCs |
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What are STABLE cells?
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Cells that are resting in G0, but can be bumped to re-enter the cell cycle w/ stimulation
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What are 2 examples of Stable cells?
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-Hepatocytes
-Lymphocytes |
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What are LABILE cells?
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Cells that are actively and rapidly dividing - they never rest in G0, and have a SHORT g1
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What are 4 examples of LABILE cells?
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-Gut epithelium
-Skin -Hair follicles -Bone marrow |
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What are 2 important processes that occur on ROUGH ER?
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1. Synth of SECRETORY proteins that get EXPORTED
2. Addition of N-linked oligosaccharides to many proteins |
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What is rER in neurons called? What does it function to do?
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NISSL substance
-Makes peptid NT's and enzymes |
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What are 2 cell types that are particularly rich in RER?
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-Plasma cells - make Antibody
-Small intestine Goblet cells - make mucous |
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What 2 important processes occur on SMOOTH ER?
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-Steroid hormone synthesis!
-Detoxification of drugs/poisons (microsomal p450 system) |
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What are 2 cell types that are particularly rich in SER?
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-Hepatocytes
-Steroid producing cells of the Adrenal Cortex |
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What are 3 general functions of the GOLGI apparatus?
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-Distribution center
-Modifies things -Makes Proteoglycans |
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What is the Golgi a distribution center for?
-input -outputs |
Proteins and Lipids from ER to:
-Plasma membrane -Lysosomes -Secretory vesicles |
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How does the Golgi target proteins to lysosomes?
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By adding MANNOSE-6-PHOSPHATE to proteins which targets them to the lysosome
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What disease is charactized by failure of Mannose-6-phosphate addition to lysosomal proteins?
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I-cell disease!
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What happens to these lysosomal proteins that fail to be properly targeted to the lysosome?
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They are secreted outside the cell! Cause much degradation bc they're ENZYMES
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What are the 4 hallmark findings in I-cell disease?
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-Coarse facial features
-Corneal CLOUDING -Restricted JOINT movement -High plasma enzyme levels |
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What is the outcome of I-cell disease often?
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Fatal in childhood
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What are 3 modifications that occur in the Golgi?
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-Modifies N-oligosaccharides on Aspargn
-Adds O-oligosacch to Ser/Thr -Sulfates sugars on Proteoglycans and some Tyrosines on proteins |
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What are the 3 vesicular trafficking proteins in the Golgi?
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COPI
COPII CLATHRIN |
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What direction does COPI cause proteins to go in?
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Retrograde; from the Golgi back to the ER!
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What direction does COPII cause proteins to go in?
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Anterograde; from the RER to cis-golgi
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What is Clathrin responsible for?
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Movement of vesicles from trans-Golgi to lysosomes and the plasma membrane, then ENDOSOMEs.
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What does Clathrin allow for at the endosomes?
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Receptor-mediated Endocytosis!!
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What is a cylindrical structure that is 24 nm in diameter and has a variable length?
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A MICROTUBULE!!!
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What are Microtubules made of?
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Polymerized dimers of a-tubulin and B-tubulin
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What is bound to each dimer?
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2 GTP
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What are 3 structures in which Microtubules are important?
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-Flagella
-Cilia -Mitotic spindles |
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What are the rates of growth and collapse of Microtubules?
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Growth = SLOW
Collapse = FAST |
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What are Microtubules involved with in neurons?
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Slow axoplasmic transport
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What is an acronym for 5 drugs that act on microtubules as their mechanism?
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Maybe Taxes on Grease Vindicate Coalworkers!
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Maybe Taxes on Grease Vindicate Coalworkers
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-Mebendazole/thiabendazole
-Taxol -Griseofulvin -Vincristine -Colchicine |
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What are mebendazole/thiabendazole?
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Anti-parasitics
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What is Taxol for?
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Breast cancer
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What is Griseofulvin?
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Antifungal
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What is Vincristine?
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Anticancer
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What is Colchicine?
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Antigout
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What is a disease in which MT polymerization is defective?
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Chediak Higashi!
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What does defective MT polymerization result in in Chediak Higashi patients?
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Impaired phagocytosis - recurrent infections!
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What is the classic description of Cilia structure?
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9+2 Microtubules
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What does 9+2 MT refer to?
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There are 9 Microtubule doublets at the periphery, and 2 single MT's in the center
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What enzyme links the peripheral 9 doublets?
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Dynein ATPase
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What is the result of Dynein's linking the peripheral doublets?
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Cilia BEND
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What ARE Cilia?
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Molecular MOTORS
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What is the retrograde motor? What is the anterograde motor?
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Retro = DYNEIN
Antero = KINESIN |
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What is the disease in which cilia are INMOTILE?
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Kartagener's disease
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What is Kartagener's disease due to?
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A Dynein arm defect
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What does Kartagener's disease result in clinically?
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-Male/female infertility
-Bronchiectasis -Recurrent sinusitis |
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What congenital anomaly is Kartagener's disease associated with?
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Situs inversus
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What is the structure of the plasma membrane of cells?
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Assymetric Fluid Bilayer
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5 components of the fluid cell bilayer:
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-Phospholipid 50%
-Cholesterol - 50% -Protein -Sphingolipids -Glycolipids |
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What increases the melting temp of the phospholipid bilayer?
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More cholesterol or More long saturated FA content
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What is Phosphatidylcholine?
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Lecithin
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What are 4 FUNCTIONs of Phosphatidylcholine?
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Major component in
-RBC membrane -Myelin -Bile -Surfactant |
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What is the form of lecithin in surfactant?
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Dipalmitoyl phosphatidylcholine - DPPC
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What enzyme is Lecithin a component of and what is its funciton?
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LCAT - lecithin cholesterol acyltransferase - esterifies cholesterol
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What is the all important pump in membranes?
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Na/K ATPase
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On which SIDE of the membrane is the ATPase part of Na/K ATPase?
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CYTOPLASMIC side
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What happens to the pump during a cycle of pumping 3 Na out and 2 K in?
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It gets phosphorylated by ATP splitting into P and ADP
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What causes the release of the P?
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Incoming 2 K's
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What drug inhibits Na/K by binding to the K site?
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Oubain
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What drugs also compete for the K binding site and increase cardiac contractility?
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Cardiac glycosides - Digoxin and Digitoxin
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What is the MOST ABUNDANT PROTEIN IN THE ENTIRE HUMAN BODY?
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Collagen!
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How can you remember what tissues Collagen is found in?
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Be So Totally Cool - Read Books!
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Be So Totally Cool - Read Books stands for:
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-Bone
-Skin -Tendons -Cartilage -Reticulin -Basement membrane |
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What is 90% of collagen; in what tissues?
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90% = Collagen type I
-Bone -Skin -Tendons |
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What is type II collagen in?
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Cartilage
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What is type III collagen in?
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Reticulin of skin, bl vessels, uterus, fetal tissues, and granulation tissue.
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What is Type IV collagen in?
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Basement membrane
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In what cells is collagen synthesized?
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FIBROBLASTS
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How many steps are in Collagen synthesis? Which steps occur inside fibroblasts, and which occur outside?
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6 STEPS
1-4 inside 5-6 outside |
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What are the 4 intracellular steps of Collagen synthesis? Where does each take place?
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1. Synthesis of Preprocollagen on RER - GlyXY polypeptides
2. Hydroxylation of Pro/Lys; ER 3. Glycosylation in Golgi 4. Exocytosis of Procollagen |
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What are the X and Y amino acids in the initial Preprocollagen polypeptide?
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Proline, Hydroxyproline, or Hydroxylysine
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What happens in the ER? What does this step require?
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Proline and Lysine residues get hydroxylated - requires VITAMIN C
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What does the Glycosylation of pro-alpha chain lysine residues in the Golgi form?
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Procollagen
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What is Procollagen?
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Triple helix of 3 collagen alpha chains
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What does lack of Vit C cause?
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Failure to hydroxylate lys and proline residues in the ER - SCURVY
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What does failure of step 3 glycosylation in the Golgi cause?
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Osteogenesis imperfecta
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What step occurs after exocytosis of procollagen to the extracellular space?
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Terminal regions cleaved to produce TROPOCOLLAGEN
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What is the last step in collagen synthesis?
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Crosslinking of Tropocollagen to make Collagen fibrils
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In what disease is the peptide cleavage of terminal regions of Procollagen for making Tropocollagen defective?
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Ehlers danlos syndrome
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So what is Ehler's danlos characterized by?
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Faulty collagen synthesis
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How many types of ED are there? Which is most common?
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10 - type III is most frequently affeted.
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What are the 3 clinical features of Ehlers-Danlos syndrome?
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-Hyperextensible skin
-Tendency to bleed/bruise -Hypermobile joints |
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What is a common associated finding in Ehlers-Danlos syndromes?
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Berry aneurysms
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What is Osteogenesis imperfecta?
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Abnormal collagen synthesis due to a variety of gene defects
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What is the most common form of Osteogenesis imperfecta? Inheritance?
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Type I Collagen defect - autosomal dominant
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Why are we glad that Type II OI is not the most common form?
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Type II is fatal in utero
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What is the incidence of OI?
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1/10,000
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4 clinical manifestations of the abnormal Collagen type I in OI:
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-Brittle bones - Multiple fractures
-Blue sclera -Hearing loss -Dental imperfections |
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What should you be careful of if you see a child come in with multiple bone breaks of differening age?
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Don't just automatically assume it's child abuse!
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What is Vimentin a stain for?
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Connective tissue
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What is Desmin a stain for?
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Muscle
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What is Cytokeratin a stain for?
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Epithelial cells
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What is GFAP a stain for?
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Neuroglia - glial cells
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What is Neurofilament stain for?
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NeurONS
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What is the STRETCHY protein?
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Elastin
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Where is elastin important?
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-Lungs
-Large arteries -Elastic ligaments |
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What 2 molecules are rich in Elastin?
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Nonhydroxylated Lys and Pro!
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What is Tropoelastin?
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Elastin with a Fibrillin Scaffolding
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What is the disease of defective Fibrillin?
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Marfan's syndrome
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What breaks down Elastin?
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Elastase
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What is Elastase inhibited by?
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a1-antitrypsin
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What is a1-antitrypsin deficient in and what is the result?
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Emphesyma - overactive Elastase, loss of elastic tissue in lung alveoli, increased compliance!
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