Protease Cascades

by Greg Crowther

A protease is an enzyme that cuts a protein into smaller pieces. It turns out that many proteases exist in inactive precursor forms until another protease clips off part of their structure. This removal of a peptide turns them on, whereupon they often cleave additional proteases. The theme of proteases activating other proteases is a recurring one in biology; examples include the complement pathway of the immune system, blood clotting, and digestion of proteins. Those last two examples are covered in this song.

[Blood clotting version]

Prefix "pro" and suffix "ogen"
(Proteases, chop chop chop!)
Constitute a protein omen.
(Proteases, chop chop chop!)
They foreshadow activation
(Proteases, chop chop chop!)
Sparked by peptide liberation.
(Proteases, chop chop chop!)

What will prothrombin become?
(Shorten up the name; shorten up the protein!)
What will fibrinogen become?
(Shorten up the name; shorten up the protein!)
Active proteins building clots right up!
(Shorten up the name; shorten up the pro--)
Until other proteases interrupt.
(Shorten!)

[Digestion version]

Prefix "pro" and suffix "ogen"
(Proteases, chop chop chop!)
Constitute a protein omen.
(Proteases, chop chop chop!)
They foreshadow activation
(Proteases, chop chop chop!)
Sparked by peptide liberation.
(Proteases, chop chop chop!)

What will proelastase become?
(Shorten up the name; shorten up the protein!)
What will chymotrypsinogen become?
(Shorten up the name; shorten up the protein!)
Proteases chewing proteins up!
(Shorten up the name; shorten up the pro--)
Until other proteases interrupt.
(Shorten!)

• karaoke

• MP3 (clotting version) (demo by the Zelcro Family Singers)

• MP3 (digestion version) (demo by The Mama and The Papa)

• sheet music (with melody play-back)

Songs like this one can be used during class meetings and/or in homework assignments. Either way, the song will be most impactful if students DO something with it, as opposed to just listening.

An initial, simple follow-up activity could be to answer the study questions below. A more extensive interaction with the song might entail (A) learning to sing it, using an audio file and/or sheet music as a guide, and/or (B) illustrating it with pictures, bodily poses, and/or bodily movements. The latter activity could begin with students identifying the most important or most challenging content of the song, and deciding how to illustrate that particular content.

Kinesthetic movements for this song could, for example, focus on the "chopping" action of proteases -- which could be represented with motions for scissors, trimming shears, etc. -- and/or on the shortening of protein lengths and protein names -- which could be represented by starting with one's hands far apart and then bringing them part-way toward each other.

(1) In the context of this song, what is meant by the phrase, "Shorten up the name; shorten up the protein!"

(2) In general, is the function of proteases to activate, destroy, or protect other proteins?

(3) Of the four specific proteins listed, which one is NOT a protease?

(4) Based on the "rules" covered in the song, list the names of the active forms of the following proteins: proaccelerin (factor V), procarboxypeptidase, trypsinogen, proconvertin (factor VII).

(5) Chymotrypsin, elastase, and trypsin are all considered serine proteases. What does this mean?

(6) What is the ultimate fate of the proteases released into the digestive tract?