Term
| What targets the HIV protease of the AIDS virus? |
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Definition
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Term
| What is the role of the HIV protease in viral replication? |
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Definition
It is the ideal target.
It generates individual viral proteins |
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Term
| HIV viral replication process: |
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Definition
| Viral RNA->Viral DNA->Provirus w/ host DNA->Viral mRNA->Viral polyprotein->Individual Viral Proteins. |
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Term
| What kind of virus is the HIV virus? |
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Definition
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Term
| What is the genetic material in the AIDS virus? |
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Definition
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Term
| How do you get from virus->host? |
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Definition
Reverse trasncriptase takes viral RNA->Viral DNA.
Integrase further turns the Viral DNA into a provirus within the host |
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Term
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Definition
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Term
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Definition
| Viral DNA->Provirus within host DNA |
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Term
| What does the HIV mRNA do? |
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Definition
| Provides the genetic information for synthesis of a polyprotein. |
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Term
| What does the HIV viral polyprotein do? |
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Definition
| Proteolytic cleavage of this polyprotein by HIV protease produces the individual proteins required for viral growth and cellular inefection |
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Term
| What would happen if we could stop HIV protease from splitting the viral polyprotein? |
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Definition
| We will stop viral replication and infection. |
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Term
| Structure/Active site of the HIV protease |
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Definition
1. Protease is a dimer of identical subunits.
2. Two active site ASP's. One per subunit.
3. Active site is formed by the subunit interface. |
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Term
| What class does HIV protease belong to? |
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Definition
| Aspartyl protease class, similar to our stomach pepsin. Quickly happened b/c we know a lot about this class of enzymes. |
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Term
| Mechanism of the arpartyl class of proteases |
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Definition
1. One step, unlike serine proteases. Water is involved right away
2. Mechanism: Acid/Base Catalysis. By the 2 active site Asp's (thus their role), with a tetrahedral intermediate formed by attack of water on peptide bond to be cleaved.
3. Key: tetrahedral transition state/intermediate is tightly bound to the HIV protease active site to stabalize it. |
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Term
| How many steps are the aspartyl class? |
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Definition
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Term
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Definition
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Term
| What kind of intermediate is formed by the attack of water on the peptide bond to be cleaved? |
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Definition
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Term
| What does the tetrahedral transition state do? |
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Definition
| Tightly binds the intermediate to HIV protease to stabilize it. |
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Term
| What happens to the Ea as the intermediate is bound more tightly to the HIV protease? |
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Definition
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Term
| What do compounds containing a hydroxy-ethylene group do? |
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Definition
| Tightly bound competitive inhibitors as they mimic the normal (tightly bound tetrahedral intermediate). Like the intermediate the hydroxy sits between the two active sites when inhibitor is bound. |
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Term
| Commonly used HIV protease inhibitor drugs |
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Definition
Invirase, Vrixivan, Viracept.
Have a hydroxy-ethylene group |
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Term
| Why is HIV protease an ideal target? |
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Definition
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Term
| What does HIV protease do? |
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Definition
| Cleaves gag-pol polypeptides |
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Term
| Target process of penicillin action? |
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Definition
| Bacterial peptidoglycan CW synthesis |
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Term
| Peptidoglycan CW structure. |
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Definition
Pentaglycine
D-ALA
Gly-D-ALA crosslink
NAM-NAG Polysaccharide repeasts
Tetrapeptide |
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Term
| Target enzyme in peptidoglycan CW synthesis |
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Definition
| Trans-peptidase (Gly->DALA) that catalyzes the last step in CW synthesis. Formation of the stable cross link |
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Term
| How do penacillins stop formation of stable CW? |
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Definition
| Stops formation of the final stable crosslink between D-ALA and Gly |
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Term
| What is the intermediate in the normal reaction mechanism for CW synthesis in bacteria? |
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Definition
| Acetyl enzyme intermediate as the D-ALA D-ALA is cleaved |
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Term
| How many steps are in the normal reaction mechanism of bacterial CW synthesis? |
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Definition
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Term
| Key features of penicillin |
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Definition
Beta-lactam ring- mimics substrate peptide bond and the four membered ring is strained and thus very reactive
Free carboxyl
Two methyl groups (mimic the C terminal D-ALA/D-ALA of the normal substrate) |
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Term
| Why is the beta lacatm ring so reactive? |
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Definition
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Term
| Since the Penicillin has a - charge it forms what kind of bond with what? Amino Acid type? |
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Definition
It forms an ionic bond w/ + charge
Basic amino acids w/ high charge. Want the inhibitor to have a - charge. |
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Term
| What kind of inhibitor is penicillin? |
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Definition
| Irreversible suicide inactivator of trans-peptidase. |
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Term
| Why does penicillin work? |
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Definition
| Because the enzyme thinks it is a normal substrate |
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Term
| What kind of intermediate is formed in the penicillin reaction? |
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Definition
acyl-intermediate w/ serine.
Chemistry is done on the inhibitor (penicillin is changed) |
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Term
| What happens to the penicillyl-enzyme complex? |
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Definition
| It becomes inactive, and thus kills the enzyme. |
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Term
| What happens after penicillin binds to transpeptidase? |
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Definition
Beta lactam ring is broken open.
Bond is formed between serine and penacillin.
Now have penicillin-enz complex
Inactive |
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Term
| What happens to the CW of the bacterium? |
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Definition
The weakened cell wall is subject to osmotic stress because the inside of the cell has higher osmolarity (CW keeps from expanding).
The weakened CW lyses and dies. |
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Term
| Bacterial resistance to penicillin |
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Definition
Beta-lactamase from bacteria
TB example
Certain resistant mutants become predominant |
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Term
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Definition
| Combined with amoxicillin to form augmentin |
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Term
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Definition
| Clavulante acid inactivates beta-lactamase to protect penicillin. |
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Term
| What does beta-lactamase do to ring? |
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Definition
| Hydrolyses it (looks like gannett reaction) |
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Term
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Definition
| Polyhydroxy aldehydes ; Monosaccharide |
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Term
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Definition
| Polyhydroxy ketone (monosaccharide) |
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Term
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Definition
| Defined by isomers of glyceraldehydes, most common in mammals |
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Term
| Common chain length of monosaccharides? |
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Definition
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Term
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Definition
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Term
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Definition
Glyceraldehyde
Dihydroxyacetone |
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Term
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Definition
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Term
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Definition
| Gluctose, fructose, galactose |
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Term
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Definition
| Differ in configuration @ one chiral carbon |
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Term
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Definition
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Term
| What kind of sugars do we use? |
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Definition
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Term
| Open chain and ring (cyclic) forms of carbohydrates are constantly what? |
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Definition
| In rapid equilibrium, constantly opening and closing |
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Term
| Where do carbohydrate rings open and close? |
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Definition
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Term
| Anomeric carbon in aldehydes? |
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Definition
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Term
| Anomeric carbon in ketones? |
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Definition
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Term
| How does interconversion of alpha and beta anomers occur? |
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Definition
| By the process of mutarotation, involving open chain and ring forms. |
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Term
| In Haworth drawing, if anomeric -OH points up is it alpha or beta? |
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Definition
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Term
| If you attack above the plane what form do you make? |
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Definition
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Term
| If you attack below the plane what form do you make? |
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Definition
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Term
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Definition
| Going from alpha to beta or vice versa |
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Term
Sugar Phosphates
Deoxy sugars
Amino Sugars
Sugar Alcohols
Sugar Acids |
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Definition
| Deriviatives of monosaccharides |
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Term
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Definition
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Term
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Definition
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Term
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Definition
Amino group replaces hydroxyl
Glycoproteins; glycoside lipids |
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Term
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Definition
Neutral Compounds
Glycerol |
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Term
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Definition
| Two monosaccharides attached w/ glycosidic linkage involving 1 anomeric carbon |
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Term
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Definition
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Term
| Three important dietary disaccharides |
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Definition
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Term
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Definition
Disaccharie
Glucose+Glucose
Major component of starch |
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Term
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Definition
Disaccharide
Glucose + Fructose
Table Sugar |
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Term
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Definition
Glucose+Galactose
Milk Sugar
Disaccharide |
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Term
| What can anomeric carbons on disaccharides link to? |
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Definition
| They can link to other species,such as nucleosides and glycoproteins. |
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Term
| Examples of polysaccharides |
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Definition
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Term
| What are starch and glycogen polymers of? |
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Definition
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Term
| Two main components of starch |
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Definition
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Term
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Definition
Alpha 1.4 linked glucose
Linear |
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Term
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Definition
| Alpha 1.4 links plus alpha 1.6 branches |
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Term
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Definition
Like amylopectin
Alpha 1.4 linear
Alpha 1.6 branched |
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Term
| What is the structure of amylopectin similar to? |
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Definition
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Term
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Definition
| In general, proteins w/ carbohydrates attached. |
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Term
| Where are glycoproteins typically found? |
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Definition
| On the extracellular or outer surface of a cells' PM |
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Term
| Two main types of covalent sugar attachments to amino acids |
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Definition
O-glycosidic Bond
N-glycosidic Bond |
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Term
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Definition
Attach sugar to glycoproteins
To SER, THR, Hydroxy-Lys of collagen |
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Term
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Definition
Attach sugars to glycoproteins
To ASN or the N terminal amino groups of hemoglobin chains. (NOT gluatmine) |
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Term
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Definition
| The level of glycosylated hemoglobin (glucose) in our RBC over the span of 120 days. |
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Term
| What is level of HbA1C in diabetics? |
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Definition
| Elevated above the normal 6% |
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Term
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Definition
| Glycoproteins that are primarily carbohydrate. |
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Term
| Where to proteoglycans occur? |
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Definition
| Mainly in the extracellular matrix or in CT of body. |
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Term
| Proteoglycans are prominent components of what? |
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Definition
| Cartilage, Tendons, Ligaments, Blood Vessels |
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Term
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Definition
| Long unbranched chains of disaccharide repeats. Sulfated |
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Term
| What is the most common gag |
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Definition
| Chondritan Sulfate, common on proteoglycans |
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Term
| What is the most sulfated gag? |
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Definition
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Term
| What is the significance of the high density negative charges on gags? Where do they come from? |
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Definition
From COO- and SO3-
Draws in Na, followed by water, resulting in the ability to cushion cartilage and libricate joints. |
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Term
| What are GAG's attached to? |
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Definition
| Covalently attached to ASN (N-linked) or SER (O-linked) in CORE protein to form a proteoglycan. |
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Term
| What do proteoglycans look like? |
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Definition
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Term
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Definition
Non Sulfated Gag
It's HUGE |
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Term
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Definition
| Covalently linked to GAG; form proteoglycan |
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Term
| How are gag's bound to form proteoglycans? |
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Definition
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Term
| What contains aggregates of proteoglycans? |
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Definition
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Term
| How are aggregates of proteoglycans linked in collagen? |
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Definition
| They are NON-COVALENTLY attached to GAG (hyaluronic acid) via LINK protein |
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Term
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Definition
| aggregates of proteoglycans in collagen are attached to these link proteins NON-covalently. |
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Term
| What is the structure of an aggregate of proteoglycans. |
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Definition
| A core protein of proteoglycans, we have a link protein holding them together. |
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Term
| In forming the aggregate, there are non-covalent interactions. What types of NC interactions mostly occur? |
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Definition
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Term
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Definition
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