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115 Cards in this Set

  • Front
  • Back
How can enzyme concentrations be altered for enzyme regulation?
By synthesis/destruction
What is an example of covalent modification that regulates enzymes?
Phosphorylation
What are some enzymes that undergo proteolytic modification as a method of their regulation?
Zymogens
What is allosteric regulation of enzymes illustrated by?
Feedback inhibition
What proteins are capable of transcriptional regulation of enzymes?
Steroid hormones
What are the phases of the cell cycle?
G1, S, G2, M
What is the SHORTEST phase in the cell cycle?
Mitosis!
What does Mitosis consist of?
-Prophase
-Metaphase
-Anaphase
-Telophase
What phases are of VARIABLE duration?
G0 and G1
What regulates the checkpoints that control transitions between phases?
-Cyclins
-CDKs
-Tumor suppressors
What is the guardian of the genome?
P53 tumor suppressor gene
What are PERMANENT cells?
Cells that remain in G0 and are terminally differentiated. Can't back out.
What are 4 examples of Permanent cells?
-Neurons
-Cardiac muscle
-Skeletal muscle
-RBCs
What are STABLE cells?
Cells that are resting in G0, but can be bumped to re-enter the cell cycle w/ stimulation
What are 2 examples of Stable cells?
-Hepatocytes
-Lymphocytes
What are LABILE cells?
Cells that are actively and rapidly dividing - they never rest in G0, and have a SHORT g1
What are 4 examples of LABILE cells?
-Gut epithelium
-Skin
-Hair follicles
-Bone marrow
What are 2 important processes that occur on ROUGH ER?
1. Synth of SECRETORY proteins that get EXPORTED
2. Addition of N-linked oligosaccharides to many proteins
What is rER in neurons called? What does it function to do?
NISSL substance
-Makes peptid NT's and enzymes
What are 2 cell types that are particularly rich in RER?
-Plasma cells - make Antibody

-Small intestine Goblet cells - make mucous
What 2 important processes occur on SMOOTH ER?
-Steroid hormone synthesis!
-Detoxification of drugs/poisons (microsomal p450 system)
What are 2 cell types that are particularly rich in SER?
-Hepatocytes
-Steroid producing cells of the Adrenal Cortex
What are 3 general functions of the GOLGI apparatus?
-Distribution center
-Modifies things
-Makes Proteoglycans
What is the Golgi a distribution center for?
-input
-outputs
Proteins and Lipids from ER to:
-Plasma membrane
-Lysosomes
-Secretory vesicles
How does the Golgi target proteins to lysosomes?
By adding MANNOSE-6-PHOSPHATE to proteins which targets them to the lysosome
What disease is charactized by failure of Mannose-6-phosphate addition to lysosomal proteins?
I-cell disease!
What happens to these lysosomal proteins that fail to be properly targeted to the lysosome?
They are secreted outside the cell! Cause much degradation bc they're ENZYMES
What are the 4 hallmark findings in I-cell disease?
-Coarse facial features
-Corneal CLOUDING
-Restricted JOINT movement
-High plasma enzyme levels
What is the outcome of I-cell disease often?
Fatal in childhood
What are 3 modifications that occur in the Golgi?
-Modifies N-oligosaccharides on Aspargn
-Adds O-oligosacch to Ser/Thr
-Sulfates sugars on Proteoglycans and some Tyrosines on proteins
What are the 3 vesicular trafficking proteins in the Golgi?
COPI
COPII
CLATHRIN
What direction does COPI cause proteins to go in?
Retrograde; from the Golgi back to the ER!
What direction does COPII cause proteins to go in?
Anterograde; from the RER to cis-golgi
What is Clathrin responsible for?
Movement of vesicles from trans-Golgi to lysosomes and the plasma membrane, then ENDOSOMEs.
What does Clathrin allow for at the endosomes?
Receptor-mediated Endocytosis!!
What is a cylindrical structure that is 24 nm in diameter and has a variable length?
A MICROTUBULE!!!
What are Microtubules made of?
Polymerized dimers of a-tubulin and B-tubulin
What is bound to each dimer?
2 GTP
What are 3 structures in which Microtubules are important?
-Flagella
-Cilia
-Mitotic spindles
What are the rates of growth and collapse of Microtubules?
Growth = SLOW
Collapse = FAST
What are Microtubules involved with in neurons?
Slow axoplasmic transport
What is an acronym for 5 drugs that act on microtubules as their mechanism?
Maybe Taxes on Grease Vindicate Coalworkers!
Maybe Taxes on Grease Vindicate Coalworkers
-Mebendazole/thiabendazole
-Taxol
-Griseofulvin
-Vincristine
-Colchicine
What are mebendazole/thiabendazole?
Anti-parasitics
What is Taxol for?
Breast cancer
What is Griseofulvin?
Antifungal
What is Vincristine?
Anticancer
What is Colchicine?
Antigout
What is a disease in which MT polymerization is defective?
Chediak Higashi!
What does defective MT polymerization result in in Chediak Higashi patients?
Impaired phagocytosis - recurrent infections!
What is the classic description of Cilia structure?
9+2 Microtubules
What does 9+2 MT refer to?
There are 9 Microtubule doublets at the periphery, and 2 single MT's in the center
What enzyme links the peripheral 9 doublets?
Dynein ATPase
What is the result of Dynein's linking the peripheral doublets?
Cilia BEND
What ARE Cilia?
Molecular MOTORS
What is the retrograde motor? What is the anterograde motor?
Retro = DYNEIN

Antero = KINESIN
What is the disease in which cilia are INMOTILE?
Kartagener's disease
What is Kartagener's disease due to?
A Dynein arm defect
What does Kartagener's disease result in clinically?
-Male/female infertility
-Bronchiectasis
-Recurrent sinusitis
What congenital anomaly is Kartagener's disease associated with?
Situs inversus
What is the structure of the plasma membrane of cells?
Assymetric Fluid Bilayer
5 components of the fluid cell bilayer:
-Phospholipid 50%
-Cholesterol - 50%
-Protein
-Sphingolipids
-Glycolipids
What increases the melting temp of the phospholipid bilayer?
More cholesterol or More long saturated FA content
What is Phosphatidylcholine?
Lecithin
What are 4 FUNCTIONs of Phosphatidylcholine?
Major component in
-RBC membrane
-Myelin
-Bile
-Surfactant
What is the form of lecithin in surfactant?
Dipalmitoyl phosphatidylcholine - DPPC
What enzyme is Lecithin a component of and what is its funciton?
LCAT - lecithin cholesterol acyltransferase - esterifies cholesterol
What is the all important pump in membranes?
Na/K ATPase
On which SIDE of the membrane is the ATPase part of Na/K ATPase?
CYTOPLASMIC side
What happens to the pump during a cycle of pumping 3 Na out and 2 K in?
It gets phosphorylated by ATP splitting into P and ADP
What causes the release of the P?
Incoming 2 K's
What drug inhibits Na/K by binding to the K site?
Oubain
What drugs also compete for the K binding site and increase cardiac contractility?
Cardiac glycosides - Digoxin and Digitoxin
What is the MOST ABUNDANT PROTEIN IN THE ENTIRE HUMAN BODY?
Collagen!
How can you remember what tissues Collagen is found in?
Be So Totally Cool - Read Books!
Be So Totally Cool - Read Books stands for:
-Bone
-Skin
-Tendons
-Cartilage
-Reticulin
-Basement membrane
What is 90% of collagen; in what tissues?
90% = Collagen type I
-Bone
-Skin
-Tendons
What is type II collagen in?
Cartilage
What is type III collagen in?
Reticulin of skin, bl vessels, uterus, fetal tissues, and granulation tissue.
What is Type IV collagen in?
Basement membrane
In what cells is collagen synthesized?
FIBROBLASTS
How many steps are in Collagen synthesis? Which steps occur inside fibroblasts, and which occur outside?
6 STEPS
1-4 inside
5-6 outside
What are the 4 intracellular steps of Collagen synthesis? Where does each take place?
1. Synthesis of Preprocollagen on RER - GlyXY polypeptides
2. Hydroxylation of Pro/Lys; ER
3. Glycosylation in Golgi
4. Exocytosis of Procollagen
What are the X and Y amino acids in the initial Preprocollagen polypeptide?
Proline, Hydroxyproline, or Hydroxylysine
What happens in the ER? What does this step require?
Proline and Lysine residues get hydroxylated - requires VITAMIN C
What does the Glycosylation of pro-alpha chain lysine residues in the Golgi form?
Procollagen
What is Procollagen?
Triple helix of 3 collagen alpha chains
What does lack of Vit C cause?
Failure to hydroxylate lys and proline residues in the ER - SCURVY
What does failure of step 3 glycosylation in the Golgi cause?
Osteogenesis imperfecta
What step occurs after exocytosis of procollagen to the extracellular space?
Terminal regions cleaved to produce TROPOCOLLAGEN
What is the last step in collagen synthesis?
Crosslinking of Tropocollagen to make Collagen fibrils
In what disease is the peptide cleavage of terminal regions of Procollagen for making Tropocollagen defective?
Ehlers danlos syndrome
So what is Ehler's danlos characterized by?
Faulty collagen synthesis
How many types of ED are there? Which is most common?
10 - type III is most frequently affeted.
What are the 3 clinical features of Ehlers-Danlos syndrome?
-Hyperextensible skin
-Tendency to bleed/bruise
-Hypermobile joints
What is a common associated finding in Ehlers-Danlos syndromes?
Berry aneurysms
What is Osteogenesis imperfecta?
Abnormal collagen synthesis due to a variety of gene defects
What is the most common form of Osteogenesis imperfecta? Inheritance?
Type I Collagen defect - autosomal dominant
Why are we glad that Type II OI is not the most common form?
Type II is fatal in utero
What is the incidence of OI?
1/10,000
4 clinical manifestations of the abnormal Collagen type I in OI:
-Brittle bones - Multiple fractures
-Blue sclera
-Hearing loss
-Dental imperfections
What should you be careful of if you see a child come in with multiple bone breaks of differening age?
Don't just automatically assume it's child abuse!
What is Vimentin a stain for?
Connective tissue
What is Desmin a stain for?
Muscle
What is Cytokeratin a stain for?
Epithelial cells
What is GFAP a stain for?
Neuroglia - glial cells
What is Neurofilament stain for?
NeurONS
What is the STRETCHY protein?
Elastin
Where is elastin important?
-Lungs
-Large arteries
-Elastic ligaments
What 2 molecules are rich in Elastin?
Nonhydroxylated Lys and Pro!
What is Tropoelastin?
Elastin with a Fibrillin Scaffolding
What is the disease of defective Fibrillin?
Marfan's syndrome
What breaks down Elastin?
Elastase
What is Elastase inhibited by?
a1-antitrypsin
What is a1-antitrypsin deficient in and what is the result?
Emphesyma - overactive Elastase, loss of elastic tissue in lung alveoli, increased compliance!