The River of Enzymes

This parody (written by Greg Crowther) is sung to the tune of "The River Of Dreams" (written and performed by Billy Joel).

In this song, the singer-scientist struggles to understand how flux through biochemical pathways is controlled. He dismisses the concept of the "rate-limiting" enzyme as overly simplistic but finds the theory of distributed control unsatisfying in that it does not explain how cells achieve large changes in flux.

A more complete scholarly treatment of these issues may be found in articles by Srere (Biol. Chem. Hoppe-Seyler 374: 833-42, 1993) and Fell & Thomas (Biochem. J. 311: 35-9, 1995).

In the middle of the lab (middle of the lab),
I am sitting at my desk (I am sitting at my desk)
With a mountain of books (mountain of books)
Piled up to my chest (up to my chest).

I must be looking for insight (looking for insight)
Into how a cell works (how a cell works),
But a cell is a maze (cell is a maze)
Of biochemical quirks (biochemical quirks).

And even though a given pathway is long,
The rate of flux can vary by severalfold.
I don't know how cells achieve this range,
But I would like to find out before I get too old.

In the middle of the lab (middle of the lab),
I am reading a review (I am reading a review)
Which is making a claim (making a claim)
That is simply not true (simply not true).

It says all of the changes (all of the changes)
In a flux over time (flux over time)
Are under the control (under the control)
Of a single enzyme (single enzyme).

I don't know why so many scientists try
To assign one step a rate-limiting role.
A mathematical analysis shows
That the steps in a pathway share the control.

In the middle of the night (middle of the night),
I am pondering a hole (I am pondering a hole) --
A big hole in our knowledge (hole in our knowledge)
Of distributed control (distributed control).

If the flux increases (flux increases)
Through a chain of enzymes (chain of enzymes),
How do they get turned on (get turned on)
All at the same time
In the middle of the night?
(I go working in the, in the laboratory)
(I go working in the, in the laboratory)
(I go working in the, in the laboratory)
(I go working in the, in the laboratory)

[repeat/ad lib/fade]