allosteric enzyme

What is a committed step in a pathway? [HOMEWORK Q1]

A step whose product can proceed only into that pathway, not other pathways.

What enzymes generally catalyze committed steps? [HOMEWORK Q1]

Allosteric enzymes.

What shape is an allosteric enzyme activity curve? [HOMEWORK Q2]

Sigmoidal (S-shaped).

What shape is a Michaelis-Menten enzyme curve? [HOMEWORK Q2]

Hyperbolic.

What can regulate allosteric enzyme activity? [HOMEWORK Q2]

Modulator molecules.

How do allosteric enzymes typically compare structurally with MM enzymes in the homework?

Allosteric enzymes are typically multimeric; MM enzymes do not tend to be multimeric.

Which enzymes are more sensitive to changes in [S] near the response threshold? [HOMEWORK Q2]

Allosteric enzymes.

What is an allosteric modulator?

A molecule that changes protein activity by binding at a regulatory site.

What is an allosteric site?

A regulatory binding site distinct from the catalytic active site.

What does a positive modulator do to a sigmoidal curve? [HOMEWORK Q3]

Shifts the curve left and lowers the threshold [S].

What does a negative modulator do to a sigmoidal curve? [HOMEWORK Q3]

Shifts the curve right and raises the threshold [S].

What is threshold [S]? [HOMEWORK Q3]

Minimum substrate concentration required for significant enzyme activity.

What is positive cooperativity?

Binding at one site increases the likelihood or affinity of binding at other sites.

What is negative cooperativity?

Binding at one site reduces affinity at other sites.

What is a homotropic effector?

A ligand that is also the substrate or primary ligand.

What is a heterotropic effector?

A regulatory molecule different from the substrate or primary ligand.

What is the T state?

Tense conformation, typically lower-affinity in the basic model.

What is the R state?

Relaxed conformation, typically higher-affinity in the basic model.

What is the concerted model of cooperativity? [HOMEWORK Q4]

Subunits switch together between T and R; ligand binding shifts equilibrium toward R.

What is the other name for the concerted model?

Monod-Wyman-Changeux (MWC) model.

What is the sequential model of cooperativity? [HOMEWORK Q4]

Ligand binding changes one subunit and progressively influences neighboring subunits.

What is the other name for the sequential model?

Koshland-Némethy-Filmer (KNF) model.

Can mixed T and R subunits occur in the sequential model?

Yes.

In the simple concerted model, are all subunits in the same conformation at once?

Yes.

What is feedback inhibition?

End product of a pathway inhibits an earlier enzyme in that pathway.

What is the purpose of feedback inhibition?

Prevent unnecessary synthesis of pathway product.

What disease does the allosteric homework specifically ask you to explain? [HOMEWORK Q5]

Gout.

What substance accumulates in gout?

Uric acid (urate).

What are purines degraded to in humans?

Uric acid.

What does PRPP stand for? [HOMEWORK Q5]

5-Phosphoribosyl-1-pyrophosphate.

What does PRS stand for in purine metabolism? [HOMEWORK Q5]

PRPP synthetase (ribose-phosphate pyrophosphokinase).

What substrates make PRPP? [HOMEWORK Q5]

Ribose-5-phosphate and ATP.

What products form when PRPP synthetase acts? [HOMEWORK Q5]

PRPP and AMP.

What is the PRPP formation reaction? [HOMEWORK Q5]

Ribose-5-phosphate + ATP → PRPP + AMP.

What does the homework explicitly say about PRPP structures? [HOMEWORK Q5]

Know ribose-5-P + ATP → PRPP + AMP structures; ATP/AMP base need not be drawn.

What uric-acid-related structure is specifically required? [HOMEWORK Q5]

Uric acid structure; know allopurinol resembles uric acid, but not allopurinol structure.

What drug is commonly used to reduce uric acid production?

Allopurinol.

What enzyme does allopurinol inhibit?

Xanthine oxidase.

How does xanthine oxidase relate to gout?

It contributes to uric acid production from purine breakdown.

What fold change in [S] was calculated for allosteric enzyme in homework Q7?

2.65/1.25 = 2.12-fold.

What fold change in [S] was calculated for MM enzyme in homework Q7?

2/0.05 = 40-fold.

Which enzyme in homework Q7 needed less [S] increase for the response?

Allosteric enzyme: 2.12-fold versus 40-fold for MM enzyme.

What did homework Q8 ask conceptually?

The opposite comparison to Q7; consult the marked graph for exact values.

What is the most important curve-shift recognition rule?

Positive modulator = left; negative modulator = right.