Chapter 8: I’m too sexy for the groceries
Learning Objectives
1.
Describe the order of operations when you mix enzyme, cofactor, and substrate.
 First the enzyme binds the substrate in the active site, then bonds are formed, and a
conformational change is elicted in the enzyme. The cofactor, residing in the active site,
assists in the formation of a transition-state complex, which is then stabilized by additional
bonding to the enzyme. Products are produced and spitten out of the enzyme, which reverts
to its prior state.
2.

3.
In general. what are the most potent inhibtors of enzymes? What are abzymes?
Those compounds that resemble the transition state, “transition state analouges,” will bind
most tightly. Abzymes are catalytic antibodies for enzymes that target the active site, such as
cocaine esterase

What is the catalytic triad of chymotrypsin?
Asp-his-ser triad creates a strong nucleophilic atacking group

Which enzyme can’t use histidine in its catalytic group? What does it use instead?
Pepsin has to use aspartate instead of histidine (pKa = 6.0) because the acidic environment of
the stomach would protonate histidine. So there’s a double Asp-Asp in the catalytic group

Why does alcohol accelerate the degredation of pyridoxal phosphate?
Alcohol displaces pyridoxal phosphate from its protein binding sites and hastens its demise
4.
5.
6. Which AAs can participate in covalent catalysis? What about acid-base catalysis?
 Most of the polar amino acids take part directly in catalysis; specifically for covalent catalysis:
serine, cysteine, lysine, & histidine
 The AAs used in acid base catalysis are histidine and aspartate
7.



8.
What is the reactive group of CoASH, biotin, and PLP (each is different)?
CoASH has a reactive –SH that forms thioesters with acyl groups
Biotin has a reactive –NH– that reacts with “CO2” groups
Pyridoxal phosphate has a reactive aldehyde that forms a covalent intermediate with AAs’
amino groups
Which coenzyme does lactate dehydrogenease require to pull a hydride off of lactose?
 Lactate dehydrogenase uses NAD+ as the hydride receptor
9.


What is produced by alcohol dehydrogenase? What metal ion plays a part?
Highly reactive, toxic, and immunogenic acetaldehyde is produced by alcohol dehydrogenase
Alcohol dehydrogenase relies on zinc to stabilize negative charge in this reaction
10. Why is di-isopropyl phosphofluoridate poisonous?
 DFP irreversibly forms a covalent intermediate in the active site of phosphodiesterase,
preventing the enzyme from digesting cAMP
DFP=>PDE
11. Which transition-state analog binds tightly to glycopeptidyl transferase?
 Bacteria use glycopeptidyl transferase for cell wall synthesis, and penicillin is a “suicide
inhibitor”of this enzyme
12. Allopurinol should prescribed for which condition?
 Allopurinol inhibits xanthanine oxidase, which produces uric acid. Uric acid crystalizes to form
sodium urate crystals in the disorder gout.
13. How is malaoxon different from DFP?
 Malaoxon’s binds with acetylcholinesterase, and reversibly, however an irreversible complex
eventually does form
14. What bonds can be broken in hydrolysis reactions?
 C-O, C-N, and C-S bonds
(onions make you cry) (COCCS CaN also)
15. Which enzyme rearranges the atoms of a molecule?
 Isomers are created by isomerase
16. C-C bonds can be broken by which class of enzymes?
 C-C, C-O, and C-N bonds can be cleaved by lysases
17. Where do synthetases derive energy for new bond formation from?
 Synthetases derive energy for new bond formation from cleavage of “high-energy phosphate
bonds”
 Differ from parent group ligases, which use ATP