Term
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Definition
| protease that catalyzes the cleavage of peptide bond where the AA on n-terminal side of bond is usually F,Y, or W. |
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Term
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Definition
| catalytic triad AA- S-H-D |
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Term
| catalytic triad are -- proteases |
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Definition
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Term
| chymotrypsin is specific in the sense that it catalyzes the cleavage of a peptide bond only if that bond is to the C-terminal side of |
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Definition
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Term
| What is common about F, Y and W? |
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Definition
| They all have bulky aromatic hydrophobic side groups. (Yes, Y has an acidic side group, but in the typical biological pH range, most of the phenolic side group is in the uncharged acidic form.) |
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Term
| why chymotrypsin only binds f y w? |
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Definition
| Adjacent to the catalytic triad is a binding pocket in chymotrypsin. This binding pocket is lined with hydrophobic amino-acid residues. Of the twenty amino acids, only the side groups of F, Y and W fit into this pocket and interact (via hydrophobic interactions) with the pocket |
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Term
| cymotrypsin has specific specificity bc: |
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Definition
| an enzyme can catalyze a reaction only after the substrate(s) have bound to the substrate-binding site, |
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Term
| trypsin has the same catalytic mechanism as -- but it catalyzes the cleavage of --? |
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Definition
trypsin
catalyzes the cleavage of a peptide bond only if that bond is to the C-terminal side of K or R (and is not a terminal peptide bond)? |
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Term
| What is common about K and R? |
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Definition
| They both have side chains that are long and carry a positive charge. The binding pocket for trypsin is similar to that for chymotrypsin, except that at the bottom of the pocket is a D residue with its - charge. This - charge interacts with the + charge on the side groups of K and R, resulting in the different substrate specificity for trypsin. |
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Term
| Both trypsin and chymotrypsin are synthesized in the --, released as an -- (or else pancreatic proteins would be degraded) into the --, where they are -- |
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Definition
pancrease
enzamatically inactive precursor
small intestine
activated |
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Term
| Cymotrypsin and trypsin work with many other enzymes with their individual substrate specificities, in the complete -- which are then absorbed by the intestine and carried by the blood to various tissues. |
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Definition
| enzymic degradation of dietary proteins to free amino acids, |
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Term
| -- Is another member of the serine proteases and has the same mechanism as -- but catalyzes -- |
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Definition
| chymotrypsin, but it catalyzes the cleavage of a peptide bond only if that bond is to the C-terminal side of G or (sometimes) A (and is not a terminal peptide bond)? |
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Term
| What is specific about G (and to some extent A)? |
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Definition
| It has the smallest side group of any of the 20 amino acids (and A has the second smallest). The binding pocket has the side groups of two amino-acid residues sticking out to form a physical block, resulting in a shallow binding pocket. Only G (and to some extent A) have side groups that are small enough to fit into the shallow pocket. |
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Term
| Fluorophosphates are a class of inhibitors of enzymes that have |
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Definition
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Term
| fluorophosphate the inhibitor inhibitor binds at the -- but the reactive F group then --, resulting in -- and thus -- inhibition of the enzyme |
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Definition
substrate binding site,
removes the hydroxyl H atom of the catalytic S group
covalent modification of the S
irreversible |
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Term
| Important inhibiotor of the flurorphosphate class |
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Definition
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Term
| Sarin inhibits-- an important enzyme in -- because it -- |
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Definition
| inhibit acetylcholine esterase (also termed choline esterase), an important enzyme in neural function because it inactivates acetylcholine after release of this neurotransmitter from synaptic terminals. |
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Term
| enzyme inhibitor in chemotherapy is-- |
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Definition
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Term
| 5-fluorouracil results in |
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Definition
| results in irreversible inhibition of the enzyme thymidylate synthase |
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Term
| the inhibitor is not 5-fluorouracil itself but rather a |
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Definition
| a metabolic product of 5-fluorouracil, namely 5-FdUMP Thymidylate synthase |
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Term
| 5-FdUMP Thymidylate synthase catalyzes a key step in the synthesis of DNA becaue: |
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Definition
| its product is thymidylate (dTMP, thymine + deoxyribose + phosphate at the 5' postition), a necessary precursor of DNA |
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Term
| The vitamin derivative tetrahydrofolate is --; during the thymidylate-synthase reaction, a derivative of tetrahydrofolate is -- |
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Definition
a cofactor for this reaction
oxidized to dihydrofolate |
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Term
| the mechanism includes as the last step, |
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Definition
| removal of the 5-H atom from the substrate dUMP (uracil + deoxyribose + phosphate at the 5' position) to form a proton and a nucleophilic C atom. |
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Term
| 5-Fluorouracil enters the metabolic pathway for conversion of- |
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Definition
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Term
| 5-fluorouracil, via several enzyme catalyzed reactions, is converted to |
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Definition
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Term
| 5-FdUMP compound begins reaction at the |
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Definition
| active site of thymidylate synthase |
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Term
| since fluorine is such a strong nucleophilic atom (F¬ is very stable, F+ is essentially hardly ever formed), the C-F bond -- resulting in |
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Definition
| cannot be broken during the enzyme mechanism (because F+ would be the unstable product). This results in a dead-end covalent complex that irreversibly inhibits the catalytic activity of thymidylate synthase |
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Term
| 5-FdUMP is an example of a -- = -- = -- = |
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Definition
| suicide inhibitor = mechanism-based inhibitor = Trojan Horse inhibitor = binding of a substrate analogue to the binding site of an enzyme with formation of an irreversible complex via a covalent bond during the "normal" catalytic reaction |
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Term
| 5-fluorouracil inhibits DNA synthesis because |
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Definition
| DNA precursorm dTMP is inhibited |
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Term
| , 5-fluorouracil is used in treating |
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Definition
| treating colon and rectal cancer, breast cancer, gastrointestinal cancers, head and neck cancer, ovarian cancer, and basal cell carcinoma of the skin and actinic keratoses. |
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Term
| relationship between chemical structure and biological function |
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Definition
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Term
| aspartame is a dipeptide -- with the C-terminal carboxylic acid forming a -- |
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Definition
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Term
| Aspartame discovery started with: |
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Definition
| James Schlatter of Searle Pharmaceutical in Dec. 1965 |
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Term
| If the order of the amino-acid residues of aspartame is reversed (FD)-- bc if the methyl group is -- the product is -- |
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Definition
the compound is not sweet
hydrolyzed from the ester
product is bitter |
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