Term
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Definition
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Term
| Examples of drugs that act by inhibiting enzymes |
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Definition
| Blood Pressure, Antibiotics (bacterial enzyme), many more |
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Term
| How do transition state analogs work? |
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Definition
| Molecule looks a lot like transition state of normal substrate. Comes in, binds enzyme, and it can't undergo chemistry. |
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Term
| How do transition state analogs bind to the active site? |
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Definition
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Term
| Which normally has the higher affinity for the active site? Normal substrate or transition state analog? |
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Definition
Transition state analog.
Often binds more tightly & with higher affinity. |
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Term
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Definition
| Inhibitor binds, does not allow substrate in |
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Term
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Definition
| Inhibitor binds, does not allow substrate in |
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Term
| What would be the effect of vmax during competative inhibition? Why? |
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Definition
| Unchanged because if you have enough substrate present, you could still get to the vmax |
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Term
| What would be the effect of Km during competitive inhibition? |
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Definition
| It has increased, it will take more substrate to get to half maximum velocity. Because there is inhibitor bound instead of substrate. |
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Term
| What happens if affinity for inhibitor >substrate by a lot? |
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Definition
| Inhibitor only. Dead enzyme. |
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Term
| What kind of molecules does trypsin bind and why? |
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Definition
| It has a deep, negatively charged binding pocket, so it binds + charged substances like arganine well. |
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Term
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Definition
Competitive Inhibitor of trypsin.
Partial + delocalized across in a similar way.
Binds like arganine. |
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Term
| Classical Competitive inhibition |
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Definition
Inhibitor comes in, binds to A.S.
It is a structure similar to the substrate. |
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Term
| Non-classical competative inhibiton |
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Definition
Prevents substrate binding
ONLY effective @ preventing binding
Does NOT bind to the same spot as the substrate.
Only one is bound
Looks like substrate, for the most part |
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Term
| Noncompetative inhibition |
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Definition
Inhibitor binds somewhere away from A.S.
Substrate can still bind, but cannot convert to product. |
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Term
| What "Inhibitor prevents conormational change essential for turnover" |
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Definition
| Non competative inhibition |
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Term
| What happens to the value of km in non-competative inhibition? |
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Definition
| It stays the same, because the inhibitor is bound in a different place. |
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Term
| What happens to the value of Vmax in non-competative inhibition? |
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Definition
| Changes, there is no turnover. |
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Term
| What happens in non-competitive inhibition if the enzyme is a dimer? |
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Definition
Inhibit dimerization
Inhibit enzyme |
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Term
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Definition
| Inhibitor only binds when substrate is bound |
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Term
| How often does uncompetative inhibition happen? |
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Definition
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Term
| What does the graph for uncompetative inhibition look like? |
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Definition
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Term
| What does uncompetitive inhibition sometimes look like? |
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Definition
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Term
| Irreversible Inhibitors/ Suicide substrates |
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Definition
| Inhibitor binds to the active site, undergoes part of reaction mechanism, and DOESN'T leave |
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Term
| Do irreversible inhibitors depend on [substrate]? |
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Definition
| NO. Once enzyme is inhibited, it doesn't work anymore. |
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Term
| Example of suicide substrates |
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Definition
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Term
| Specificity of irreversible inhibitors |
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Definition
| Highly specific, leave enzyme dead |
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Term
| What type of inhibitors "alkylate the enzyme" |
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Definition
Irreversible inhibitors
Leave part of themselves behind. |
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Term
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Definition
Lipid products that mediate pain
They recruit other things that cause inflammation and pain. |
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Term
| What makes prosteglandins? |
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Definition
| An enzyme COX (cycloxygenase)converts arachidonic acid to precursors of prosteglandins |
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Term
| Besides prosteglandins what does COX make? |
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Definition
| Other signaling molecules in the stomach. Makes mucous to protect stomach from acid. |
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Term
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Definition
| Substrate comes in turns into prostegladin, it is the target of numerous drug inventions. |
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Term
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Definition
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Term
| Penacillin is what type of drug? |
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Definition
| Irreversible/Suicide inhibitor |
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Term
| How does penicillin work? |
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Definition
Finds a bacteria trying to make CW
Transpeptidases (cut off part of a substrate and make a cross link with another peptide) are inhibited.
*Drug reacts w/ active site serine
*Breaks the bond, important for CW formation
*After cyclic structre bond broken, it can't get there and bacteria can't make a CW, they die :) |
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Term
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Definition
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Term
| Charge effect of asprin for reactivity? |
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Definition
| Negatively charged, like aracionic acid |
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Term
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Definition
*Binds to active site of cox-1
*Transfers acetate to serine
*The substrate cannot get to the active site after this reaction
*Enzyme is dead. |
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Term
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Definition
2 isoforms
Cox-1: Stomach lining
Cox-2: Usually for pain management |
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Term
| What does asprin inhibit? |
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Definition
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Term
| Why do you begin to experience stomach problems with long term asprin use? |
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Definition
| It inhibits cox-1; which is for stomach lining. |
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Term
| What kind of inhibitor is Ibuprofen? |
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Definition
| Competative inhibitor of COX |
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Term
| What kind of inhibitor is asprin? |
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Definition
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Term
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Definition
| Was a pain medication for arthritis. People began to have heart attacks when on it. |
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Term
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Definition
Binds to active site
Doesn't modify it
While present substrate cannot get in
Competative inhibitor. |
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Term
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Definition
| Hydrolyzes Ach. to H20 plus choline |
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Term
| Active site of Acetylcholinesterase |
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Definition
| Contains Glutamine, Histadine, Serine. |
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Term
| What are inhibitors of acetylcholinesterase? |
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Definition
| Oragnophosphorous compounds |
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Term
| Acetylcholinesterase inhibitition process |
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Definition
| Serine activated by histadine Alkoxide nucleophile attacks phosphorous and forms acyl E intermediate. Normally part of substrate would leave, it doesn't Flouride leaves Forms a ligand enzyme. Water cannot hydrolyze Dead enzyme |
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Term
| What intermediate is formed in the reaction of organophosphates w/ acetylcholinesterase. |
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Definition
Aceyl-E
Can't be hydrolyzed |
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Term
| Why do nerves die when acetylcholinesterase is inhibitied? |
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Definition
| Can't remove Ach from the synaptic cleft. Neurotoxin. Nerve dies. |
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Term
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Definition
| A type of organophosphate that irreversible binds and kills the esterase. |
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Term
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Definition
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Term
| How to treat acetylcholinesterase poisoning |
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Definition
Atropine + Pralidoxime
Atropene allows poisoned person time to get esterase substitute.
"Kill one poision w/ another"
Pralidoxime - Regerates esterase
Stops noxius effects |
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Term
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Definition
Have oxeme group
Group small enough to get in
React w/ serine phosphate
Remove phosphorylated serine
"Re-activates"acetylcholinesterase |
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Term
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Definition
Have oxeme group
Group small enough to get in
React w/ serine phosphate
Remove phosphorylated serine
"Re-activates"acetylcholinesterase |
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Term
| What cellular processes are regulated? |
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Definition
Nearly all
Including: Growth, Metabolism, Motolity |
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Term
| Why are cellular processes regulated? |
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Definition
| Because they are all not needed at the same time. |
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Term
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Definition
Tightly regulated
Sometimes opposing processes
Made by one thing; broken down by another
(glucose example) |
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Term
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Definition
| Series of reactions in order to make a product |
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Term
| If you wanted to control how much product you make you.. |
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Definition
| Turn it off, if you have enough product it can feedback to a previous step |
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Term
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Definition
| Product regulates the pathway. |
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Term
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Definition
| Ex. Building up of A in order to activate enzymes of form product |
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Term
| What are the most regulated enzymes? |
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Definition
Those that catalyze a committed step.
Cannot be reversed after the committed step. |
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Term
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Definition
| When a certain decision to make product has been made: Mostly branches, irreversible. |
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Term
| How do bacteria make L-isoleucine? |
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Definition
Starting with L-Threonine
5 Enzymes
Thr-dehyrotase= committed step
When there is enough isoleucine, it feeds-back |
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Term
| How are enzymes other than the committed step regulated? |
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Definition
| By presence/Absence of substrate. |
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Term
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Definition
| Only happens at the committed step |
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Term
| Rate of all enzyme reactions depends on what? |
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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
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Term
| The amount of protein present @ any given time is controlled by what? |
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Definition
How fast is it made?
How fast is it degraded?
There is a balance for every protein. |
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Term
| Can synthesis and degredation of proteins be regulated? |
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Definition
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Term
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Definition
Gene-->PreMRNA-->MRNA-->Proprotein-->Enzyme
Transcription, RNA processing, Translation, Protein Processing |
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Term
| How fast is the biosynthesis of enzymes? |
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Definition
| Very slow, because it is multi-step. |
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Term
| Where can you regulate during bio-synthesis of enzymes? |
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Definition
At all of the steps
Transcription
RNA Processing
Translation
Protein Processing |
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Term
| Degredation of enzymes process |
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Definition
| Protein->Tag->Degrading Machinery Multi-step |
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Term
| What is the degrading machinery? |
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Definition
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Term
| Rate of protein degredation? |
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Definition
| Not fast, faster than biosynthesis |
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Term
| Are proteins regulated by their degradation? |
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Definition
| Yes, especially those needed for a short time. |
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Term
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Definition
| Rate protein is made/degraded |
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Term
| 2 ways to regulate enzymes |
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Definition
[enzyme]
Regulate activity of existing enzyme |
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Term
| What is the fastest way to regulate activity of an existing enzyme? |
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Definition
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Term
| What is the slower way to regulate activity of an existing enzyme |
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Definition
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Term
| What kind of regulation would you use for metabolism? |
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Definition
| non-covalent, since it needs to be fast. |
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Term
| How do you regulate activity of an existing enzyme? |
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Definition
Enzyme binds to regulatory molecule and becomes more/less active.
Generally small molecule |
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Term
| What do the kinetics for enzyme activity look like? |
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Definition
| S-shaped curve. Resemble hemoglobin binding curve. Can be shifted |
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Term
| How do you change the kinetics/curve of enzymes? |
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Definition
| Bind regulatory molecules to enzyme. Allosteric reguluation. They generally don't bind to active site. Change quat. structure. |
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Term
| Allosteric Enzyme Regulation |
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Definition
| Modulator is bound to place other than the active site; makes the enzyme more or less active. Transmits through quat structure to other enzymes |
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Term
| How does allosteric regulation change the structure of the enzyme? |
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Definition
| Changes the quaternary structure, then transmits change to other enzymes |
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Term
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Definition
Catalyzes committed step in glycolysis. has a regulatory site. If energy needed, something binds and activates enzyme. If there is lots of energy, it binds to other things, ex. atp.
Enzyme can be turned off; high and low affinity based on needs of cell. |
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Term
| Regulation of enzymes leads to what? |
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Definition
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Term
| Non-covalent ways to regulate enzyme activity |
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Definition
Allosteric regulation
Inhibatory peptides/proteins |
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Term
| Example of inhibitory peptides/proteins |
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Definition
| Proteases: once active; hydrolyzes until degraded. Must be regulated. |
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Term
| What do proteases bind to when they need regulated? |
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Definition
| Inhibitors. Ex. Serine protease inhibitors; bind to serine protease, block access to active site. Turn them off |
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Term
| Patella protease? Spelling |
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Definition
| Inhibitory protein binds to other protein, normally blocks access to active site until inhibitory protein comes off, if it ever does. |
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Term
| Most common covalent modificiation? |
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Definition
| Add or remove phosphates. (activates or inactivates) |
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Term
| What do kinase enzymes do? |
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Definition
| Hydrolyze ATP and add phosphates to the protein; protein is either more/less active than it was before. |
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Term
Kinase (colvalent modification) vs. Allosteric regulation
Speed |
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Definition
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Term
| Specificity of kinases/phosphatases? |
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Definition
| Very specific. Cells are full of kinases and phosphatases! |
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Term
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Definition
| Remove certain phosphates from the protein |
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Term
| What controls the equilibrium between enzyme and enzyme phosphate |
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Definition
| Kinase/phosphatases. Not just on or off. Think more on/more off |
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Term
| What amino acids are usually phosphorylated? |
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Definition
| Ser, His, Thr, Tyr (noncharged, polar) |
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Term
| Phosphate @ physiological pH (3) |
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Definition
| 2 charges (- on Os); Bigger than oH; MANY H+ bond receptors. |
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Term
| How does phosphate @ physiological pH change the enzyme conformation? |
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Definition
| It is now charged, so it repels, attracts to adjacent AA's. |
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Term
| What happens when you phosphorylate a protein? |
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Definition
Charges. Quat structure also changes. Sometimes more/less active. Shift in binding/kcat
Allowing binding to other substrates, ex. tyrosine phosphates |
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Term
| Glycogen + Inorganic phosphate? |
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Definition
| Splits off glucose 6 phosphate |
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Term
| How do you get glucose off glycogen? |
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Definition
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Term
| Glycogen phosphorylase activation? |
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Definition
| Needs to be phosphorylated by phosphorylase kinase |
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Term
| How do you turn off glycogen synthase? |
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Definition
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Term
| Binding sites of glycogen synthase? |
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Definition
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Term
| How is signal amplified in kinases? |
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Definition
Signal->Kinase(10)->Kinase (100)->Kinase (1000)
Map kinase, kinase kinase example
Each kinase works on 10 kinases |
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Term
| What are zymogens? What do they do? |
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Definition
| Precursors, prevent unneeded activity. |
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Term
| How are zymogens activated? |
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Definition
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Term
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Definition
| Same way as zymogens; run into protease |
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Term
| Example of zymogen:Gunther |
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Definition
Chymotrypsin
Biosynthesized in pancreas, runs into trypsin, hydrolyzes peptide bond.
Allows N-terminal to move allowing access to active site.
Stabalizes enzyme in active formation |
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Term
| Example of compartmentilization? |
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Definition
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Term
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Definition
Enzymes are compartmentilized
Way to regulate them
Shift from compartment->Compartment |
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Term
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Definition
| Different enzymes that catalyze the same reactions |
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Term
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Definition
Hexokinase (glucose+ADP->Undergo glycolysis)
Gluco-kinase (Kinase does exact same thing)
One has Km=50; km=10
Doesn't effectively bind @ high glucose concentration |
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Term
| What happens when regulation fails? |
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Definition
| Leads to diseases like cancer |
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Term
| What do mutant kinases without regulation cause? |
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Definition
| Unregulated cell division |
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Term
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Definition
| Comes from outside, growth factor. Binds to a receptro (tryosine kinase) |
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